Sample records for acetaldehyde metabolism influence

  1. Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds.

    PubMed Central

    Reed, T. E.; Kalant, H.; Gibbins, R. J.; Kapur, B. M.; Rankin, J. G.

    1976-01-01

    Ethanol (0.4 to 0.8 g/kg in 30 minutes) was given by mouth to 102 healthy young volunteers (37 Caucasian men, 21 Caucasian women, 20 Chinese men and 24 Ojibwa men). Venous blood concentrations of ethanol and acetaldehyde 60, 90, 120 and 150 minutes after the end of drinking were measured by gas chromatography. The calculated rates of ethanol metabolism in the Caucasian men and women did not differ, but the overall group means for subgroups of Caucasians (103.6 mg/kg-h), Chinese (136.6 mg/kg-h) and Ojibwa (182.7 mg/kg-h) with decreasing postabsorption values differed significantly from each other. Mean acetaldehyde values paralleled the rates of ethanol metabolism: Ojibwa, 14.6 mug/ml; Chinese, 10.0 mug/ml; and Caucasians, 9.4 mug/ml. The high rate of ethanol metabolism in Amerind subjects differs from previous findings. Habitual level of alcohol consumption, proportion of body fat and genetic factors appear to account for most of the group differences. PMID:991030

  2. In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism.

    PubMed

    Bakri, M M; Rich, A M; Cannon, R D; Holmes, A R

    2015-02-01

    Alcohol consumption is a risk factor for oral cancer, possibly via its conversion to acetaldehyde, a known carcinogen. The oral commensal yeast Candida albicans may be one of the agents responsible for this conversion intra-orally. The alcohol dehydrogenase (Adh) family of enzymes are involved in acetaldehyde metabolism in yeast but, for C. albicans it is not known which family member is responsible for the conversion of ethanol to acetaldehyde. In this study we determined the expression of mRNAs from three C. albicans Adh genes (CaADH1, CaADH2 and CaCDH3) for cells grown in different culture media at different growth phases by Northern blot analysis and quantitative reverse transcription polymerase chain reaction. CaADH1 was constitutively expressed under all growth conditions but there was differential expression of CaADH2. CaADH3 expression was not detected. To investigate whether CaAdh1p or CaAdh2p can contribute to alcohol catabolism in C. albicans, each gene from the reference strain C. albicans SC5314 was expressed in Saccharomyces cerevisiae. Cell extracts from an CaAdh1p-expressing S. cerevisiae recombinant, but not an CaAdh2p-expressing recombinant, or an empty vector control strain, possessed ethanol-utilizing Adh activity above endogenous S. cerevisiae activity. Furthermore, expression of C. albicans Adh1p in a recombinant S. cerevisiae strain in which the endogenous ScADH2 gene (known to convert ethanol to acetaldehyde in this yeast) had been deleted, conferred an NAD-dependent ethanol-utilizing, and so acetaldehyde-producing, Adh activity. We conclude that CaAdh1p is the enzyme responsible for ethanol use under in vitro growth conditions, and may contribute to the intra-oral production of acetaldehyde. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity

    PubMed Central

    Guidolin, Valeria; Balbo, Silvia

    2018-01-01

    Alcohol is classified by the International Agency for Research on Cancer (IARC) as a human carcinogen and its consumption has been associated to an increased risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers. Its mechanisms of carcinogenicity remain unclear and various hypotheses have been formulated depending on the target organ considered. In the case of UADT cancers, alcohol’s major metabolite acetaldehyde seems to play a crucial role. Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can result in mutations and lead to cancer development. Despite alcohol being mainly metabolized in the liver, several studies performed in humans found higher levels of acetaldehyde in saliva compared to those found in blood immediately after alcohol consumption. These results suggest that alcohol-derived acetaldehyde exposure may occur in the oral cavity independently from liver metabolism. This hypothesis is supported by our recent results showing the presence of acetaldehyde-related DNA modifications in oral cells of monkeys and humans exposed to alcohol, overall suggesting that the alcohol metabolism in the oral cavity is an independent cancer risk factor. This review article will focus on illustrating the factors modulating alcohol-derived acetaldehyde exposure and effects in the oral cavity. PMID:29342885

  4. Mystic Acetaldehyde: The Never-Ending Story on Alcoholism.

    PubMed

    Peana, Alessandra T; Sánchez-Catalán, María J; Hipólito, Lucia; Rosas, Michela; Porru, Simona; Bennardini, Federico; Romualdi, Patrizia; Caputi, Francesca F; Candeletti, Sanzio; Polache, Ana; Granero, Luis; Acquas, Elio

    2017-01-01

    After decades of uncertainties and drawbacks, the study on the role and significance of acetaldehyde in the effects of ethanol seemed to have found its main paths. Accordingly, the effects of acetaldehyde, after its systemic or central administration and as obtained following ethanol metabolism, looked as they were extensively characterized. However, almost 5 years after this research appeared at its highest momentum, the investigations on this topic have been revitalized on at least three main directions: (1) the role and the behavioral significance of acetaldehyde in different phases of ethanol self-administration and in voluntary ethanol consumption; (2) the distinction, in the central effects of ethanol, between those arising from its non-metabolized fraction and those attributable to ethanol-derived acetaldehyde; and (3) the role of the acetaldehyde-dopamine condensation product, salsolinol. The present review article aims at presenting and discussing prospectively the most recent data accumulated following these three research pathways on this never-ending story in order to offer the most up-to-date synoptic critical view on such still unresolved and exciting topic.

  5. Candida virulence and ethanol-derived acetaldehyde production in oral cancer and non-cancer subjects.

    PubMed

    Alnuaimi, A D; Ramdzan, A N; Wiesenfeld, D; O'Brien-Simpson, N M; Kolev, S D; Reynolds, E C; McCullough, M J

    2016-11-01

    To compare biofilm-forming ability, hydrolytic enzymes and ethanol-derived acetaldehyde production of oral Candida isolated from the patients with oral cancer and matched non-oral cancer. Fungal biofilms were grown in RPMI-1640 medium, and biofilm mass and biofilm activity were assessed using crystal violet staining and XTT salt reduction assays, respectively. Phospholipase, proteinase, and esterase production were measured using agar plate method, while fungal acetaldehyde production was assessed via gas chromatography. Candida isolated from patients with oral cancer demonstrated significantly higher biofilm mass (P = 0.031), biofilm metabolic activity (P < 0.001), phospholipase (P = 0.002), and proteinase (P = 0.0159) activity than isolates from patients with non-oral cancer. High ethanol-derived acetaldehyde-producing Candida were more prevalent in patients with oral cancer than non-oral cancer (P = 0.01). In univariate regression analysis, high biofilm mass (P = 0.03) and biofilm metabolic activity (P < 0.001), high phospholipase (P = 0.003), and acetaldehyde production ability (0.01) were significant risk factors for oral cancer; while in the multivariate regression analysis, high biofilm activity (0.01) and phospholipase (P = 0.01) were significantly positive influencing factors on oral cancer. These data suggest a significant positive association between the ability of Candida isolates to form biofilms, to produce hydrolytic enzymes, and to metabolize alcohol to acetaldehyde with their ability to promote oral cancer development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Alcohol and acetaldehyde in public health: from marvel to menace.

    PubMed

    Guo, Rui; Ren, Jun

    2010-04-01

    Alcohol abuse is a serious medical and social problem. Although light to moderate alcohol consumption is beneficial to cardiovascular health, heavy drinking often results in organ damage and social problems. In addition, genetic susceptibility to the effect of alcohol on cancer and coronary heart disease differs across the population. A number of mechanisms including direct the toxicity of ethanol, its metabolites [e.g., acetaldehyde and fatty acid ethyl esters (FAEEs)] and oxidative stress may mediate alcoholic complications. Acetaldehyde, the primary metabolic product of ethanol, is an important candidate toxin in developing alcoholic diseases. Meanwhile, free radicals produced during ethanol metabolism and FAEEs are also important triggers for alcoholic damages.

  7. Ethanol Metabolism by HeLa Cells Transduced with Human Alcohol Dehydrogenase Isoenzymes: Control of the Pathway by Acetaldehyde Concentration†

    PubMed Central

    Matsumoto, Michinaga; Cyganek, Izabela; Sanghani, Paresh C.; Cho, Won Kyoo; Liangpunsakul, Suthat; Crabb, David W.

    2010-01-01

    Background Human class I alcohol dehydrogenase 2 isoenzymes (encoded by the ADH1B locus) have large differences in kinetic properties; however, individuals inheriting the alleles for the different isoenzymes exhibit only small differences in alcohol elimination rates. This suggests that other cellular factors must regulate the activity of the isoenzymes. Methods The activity of the isoenzymes expressed from ADH1B*1, ADH1B*2, and ADH1B*3 cDNAs was examined in stably transduced HeLa cell lines, including lines which expressed human low Km aldehyde dehydrogenase (ALDH2). The ability of the cells to metabolize ethanol was compared with that of HeLa cells expressing rat class I ADH (HeLa-rat ADH cells), rat hepatoma (H4IIEC3) cells, and rat hepatocytes. Results The isoenzymes had similar protein half-lives in the HeLa cells. Rat hepatocytes, H4IIEC3 cells, and HeLa-rat ADH cells oxidized ethanol much faster than the cells expressing the ADH1B isoenzymes. This was not explained by high cellular NADH levels or endogenous inhibitors; but rather because the activity of the β1 and β2 ADHs were constrained by the accumulation of acetaldehyde, as shown by the increased rate of ethanol oxidation by cell lines expressing β2 ADH plus ALDH2. Conclusion The activity of the human β2 ADH isoenzyme is sensitive to inhibition by acetaldehyde, which likely limits its activity in vivo. This study emphasizes the importance of maintaining a low steady–state acetaldehyde concentration in hepatocytes during ethanol metabolism. PMID:21166830

  8. Sensory effect of acetaldehyde on the perception of 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine: Role of acetaldehyde in sensory interactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Coetzee, C.; Brand, J.; Jacobson, Daniel A.

    Background and Aims-Wine aroma is influenced by complex interactions between various wine constituents. This study investigated the sensory interactive effects of Sauvignon Blanc impact compounds, 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine, with acetaldehyde that typically forms during the oxidation of wine. Methods and Results-Spiked model wines were subjected to sensory descriptive analysis using a trained sensory panel. Additionally, the concentration of each compound varied from below aroma threshold values to high values as reported for wine. Depending on the concentration, acetaldehyde enhanced fruity attributes at a lower concentration, whereas suppression occurred at a higher concentration. Acetaldehyde effectively suppressed the green pepper aroma attributemore » at certain concentration values, whereas 3-mercaptohexan-1-ol suppressed oxidised green apple associated with acetaldehyde. Changes in attributes used for aroma description also occurred because of change in concentration. Conclusions-Complex sensory interactions may occur between Sauvignon Blanc impact compounds and one of the main oxidation-derived compounds, acetaldehyde. Acetaldehyde can enhance or suppress pleasant fruity characters depending on the concentration. Significance of the Study-This study showed the potential positive effect of acetaldehyde on white wine aroma when present at a low concentration. Formation of this compound during winemaking and ageing should, however, be controlled because of negative sensory interactions occurring at a higher concentration. In conclusion, this study may also contribute to the sensory characterisation of Sauvignon Blanc wine undergoing oxidation.« less

  9. Sensory effect of acetaldehyde on the perception of 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine: Role of acetaldehyde in sensory interactions

    DOE PAGES

    Coetzee, C.; Brand, J.; Jacobson, Daniel A.; ...

    2016-01-28

    Background and Aims-Wine aroma is influenced by complex interactions between various wine constituents. This study investigated the sensory interactive effects of Sauvignon Blanc impact compounds, 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine, with acetaldehyde that typically forms during the oxidation of wine. Methods and Results-Spiked model wines were subjected to sensory descriptive analysis using a trained sensory panel. Additionally, the concentration of each compound varied from below aroma threshold values to high values as reported for wine. Depending on the concentration, acetaldehyde enhanced fruity attributes at a lower concentration, whereas suppression occurred at a higher concentration. Acetaldehyde effectively suppressed the green pepper aroma attributemore » at certain concentration values, whereas 3-mercaptohexan-1-ol suppressed oxidised green apple associated with acetaldehyde. Changes in attributes used for aroma description also occurred because of change in concentration. Conclusions-Complex sensory interactions may occur between Sauvignon Blanc impact compounds and one of the main oxidation-derived compounds, acetaldehyde. Acetaldehyde can enhance or suppress pleasant fruity characters depending on the concentration. Significance of the Study-This study showed the potential positive effect of acetaldehyde on white wine aroma when present at a low concentration. Formation of this compound during winemaking and ageing should, however, be controlled because of negative sensory interactions occurring at a higher concentration. In conclusion, this study may also contribute to the sensory characterisation of Sauvignon Blanc wine undergoing oxidation.« less

  10. A PBPK MODEL FOR EVALUATING THE IMPACT OF ALDEHYDE DEHYDROGENASE POLYMORPHISMS ON COMPARATIVE RAT AND HUMAN NASAL TISSUE ACETALDEHYDE DOSIMETRY

    EPA Science Inventory

    ABSTRACT: Acetaldehyde is an important intermediate in chemical synthesis and a byproduct of normal oxidative metabolism of several industrially important compounds including ethanol, ethyl acetate and vinyl acetate. Chronic inhalation of acetaldehyde leads to degeneratio...

  11. A PBPK model for evaluating the impact of aldehyde dehydrogenase polymorphisms on comparative rat and human nasal tissue acetaldehyde dosimetry*

    EPA Science Inventory

    Acetaldehyde is an important intermediate in the chemical synthesis and normal oxidative metabolism of several industrially important compounds, including ethanol, ethyl acetate, and vinyl acetate. Chronic inhalation of acetaldehyde leads to degeneration of the olfactory and resp...

  12. An Optimized Method for the Measurement of Acetaldehyde by High-Performance Liquid Chromatography

    PubMed Central

    Guan, Xiangying; Rubin, Emanuel; Anni, Helen

    2011-01-01

    Background Acetaldehyde is produced during ethanol metabolism predominantly in the liver by alcohol dehydrogenase, and rapidly eliminated by oxidation to acetate via aldehyde dehydrogenase. Assessment of circulating acetaldehyde levels in biological matrices is performed by headspace gas chromatography and reverse phase high-performance liquid chromatography (RP-HPLC). Methods We have developed an optimized method for the measurement of acetaldehyde by RP-HPLC in hepatoma cell culture medium, blood and plasma. After sample deproteinization, acetaldehyde was derivatized with 2,4-dinitrophenylhydrazine (DNPH). The reaction was optimized for pH, amount of derivatization reagent,, time and temperature. Extraction methods of the acetaldehyde-hydrazone (AcH-DPN) stable derivative and product stability studies were carried out. Acetaldehyde was identified by its retention time in comparison to AcH-DPN standard, using a new chromatography gradient program, and quantitated based on external reference standards and standard addition calibration curves in the presence and absence of ethanol. Results Derivatization of acetaldehyde was performed at pH 4.0 with a 80-fold molar excess of DNPH. The reaction was completed in 40 min at ambient temperature, and the product was stable for 2 days. A clear separation of AcH-DNP from DNPH was obtained with a new 11-min chromatography program. Acetaldehyde detection was linear up to 80 μM. The recovery of acetaldehyde was >88% in culture media, and >78% in plasma. We quantitatively determined the ethanol-derived acetaldehyde in hepatoma cells, rat blood and plasma with a detection limit around 3 μM. The accuracy of the method was <9% for intraday and <15% for interday measurements, in small volume (70 μl) plasma sampling. Conclusions An optimized method for the quantitative determination of acetaldehyde in biological systems was developed using derivatization with DNPH, followed by a short RP-HPLC separation of AcH-DNP. The method has

  13. An optimized method for the measurement of acetaldehyde by high-performance liquid chromatography.

    PubMed

    Guan, Xiangying; Rubin, Emanuel; Anni, Helen

    2012-03-01

    Acetaldehyde is produced during ethanol metabolism predominantly in the liver by alcohol dehydrogenase and rapidly eliminated by oxidation to acetate via aldehyde dehydrogenase. Assessment of circulating acetaldehyde levels in biological matrices is performed by headspace gas chromatography and reverse phase high-performance liquid chromatography (RP-HPLC). We have developed an optimized method for the measurement of acetaldehyde by RP-HPLC in hepatoma cell culture medium, blood, and plasma. After sample deproteinization, acetaldehyde was derivatized with 2,4-dinitrophenylhydrazine (DNPH). The reaction was optimized for pH, amount of derivatization reagent, time, and temperature. Extraction methods of the acetaldehyde-hydrazone (AcH-DNP) stable derivative and product stability studies were carried out. Acetaldehyde was identified by its retention time in comparison with AcH-DNP standard, using a new chromatography gradient program, and quantitated based on external reference standards and standard addition calibration curves in the presence and absence of ethanol. Derivatization of acetaldehyde was performed at pH 4.0 with an 80-fold molar excess of DNPH. The reaction was completed in 40 minutes at ambient temperature, and the product was stable for 2 days. A clear separation of AcH-DNP from DNPH was obtained with a new 11-minute chromatography program. Acetaldehyde detection was linear up to 80 μM. The recovery of acetaldehyde was >88% in culture media and >78% in plasma. We quantitatively determined the ethanol-derived acetaldehyde in hepatoma cells, rat blood and plasma with a detection limit around 3 μM. The accuracy of the method was <9% for intraday and <15% for interday measurements, in small volume (70 μl) plasma sampling. An optimized method for the quantitative determination of acetaldehyde in biological systems was developed using derivatization with DNPH, followed by a short RP-HPLC separation of AcH-DNP. The method has an extended linear range, is

  14. Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

    PubMed

    Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

    2013-03-01

    Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

  15. Development of industrial brewing yeast with low acetaldehyde production and improved flavor stability.

    PubMed

    Wang, Jinjing; Shen, Nan; Yin, Hua; Liu, Chunfeng; Li, Yongxian; Li, Qi

    2013-02-01

    Higher acetaldehyde concentration in beer is one of the main concerns of current beer industry in China. Acetaldehyde is always synthesized during beer brewing by the metabolism of yeast. Here, using ethanol as the sole carbon source and 4-methylpyrazole as the selection marker, we constructed a new mutant strain with lower acetaldehyde production and improved ethanol tolerance via traditional mutagenesis strategy. European Brewery Convention tube fermentation tests comparing the fermentation broths of mutant strain and industrial brewing strain showed that the acetaldehyde concentration of mutant strain was 81.67 % lower, whereas its resistant staling value was 1.0-fold higher. Owing to the mutation, the alcohol dehydrogenase activity of the mutant strain decreased to about 30 % of the wild-type strain. In the meantime, the fermentation performance of the newly screened strain has little difference compared with the wild-type strain, and there are no safety problems regarding the industrial usage of the mutant strain. Therefore, we suggest that the newly screened strain could be directly applied to brewing industry.

  16. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci.

    PubMed

    Pavlova, Sylvia I; Jin, Ling; Gasparovich, Stephen R; Tao, Lin

    2013-07-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci.

  17. Multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase causing excessive acetaldehyde production from ethanol by oral streptococci

    PubMed Central

    Pavlova, Sylvia I.; Jin, Ling; Gasparovich, Stephen R.

    2013-01-01

    Ethanol consumption and poor oral hygiene are risk factors for oral and oesophageal cancers. Although oral streptococci have been found to produce excessive acetaldehyde from ethanol, little is known about the mechanism by which this carcinogen is produced. By screening 52 strains of diverse oral streptococcal species, we identified Streptococcus gordonii V2016 that produced the most acetaldehyde from ethanol. We then constructed gene deletion mutants in this strain and analysed them for alcohol and acetaldehyde dehydrogenases by zymograms. The results showed that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol and ethanol, respectively. Two additional dehydrogenases, S-AdhA and TdhA, were identified with specificities to the secondary alcohol 2-propanol and threonine, respectively, but not to ethanol. S. gordonii V2016 did not show a detectable acetaldehyde dehydrogenase even though its adhE gene encodes a putative bifunctional acetaldehyde/alcohol dehydrogenase. Mutants with adhE deletion showed greater tolerance to ethanol in comparison with the wild-type and mutant with adhA or adhB deletion, indicating that AdhE is the major alcohol dehydrogenase in S. gordonii. Analysis of 19 additional strains of S. gordonii, S. mitis, S. oralis, S. salivarius and S. sanguinis showed expressions of up to three alcohol dehydrogenases, but none showed detectable acetaldehyde dehydrogenase, except one strain that showed a novel ALDH. Therefore, expression of multiple alcohol dehydrogenases but no functional acetaldehyde dehydrogenase may contribute to excessive production of acetaldehyde from ethanol by certain oral streptococci. PMID:23637459

  18. Acetaldehyde

    Integrated Risk Information System (IRIS)

    Acetaldehyde ; CASRN 75 - 07 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effec

  19. Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

    PubMed

    Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

    2016-12-13

    Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

  20. The ethanol metabolite acetaldehyde increases paracellular drug permeability in vitro and oral bioavailability in vivo.

    PubMed

    Fisher, Scott J; Swaan, Peter W; Eddington, Natalie D

    2010-01-01

    Alcohol consumption leads to the production of the highly reactive ethanol metabolite, acetaldehyde, which may affect intestinal tight junctions and increase paracellular permeability. We examined the effects of elevated acetaldehyde within the gastrointestinal tract on the permeability and bioavailability of hydrophilic markers and drug molecules of variable molecular weight and geometry. In vitro permeability was measured unidirectionally in Caco-2 and MDCKII cell models in the presence of acetaldehyde, ethanol, or disulfiram, an aldehyde dehydrogenase inhibitor, which causes acetaldehyde formation when coadministered with ethanol in vivo. Acetaldehyde significantly lowered transepithelial resistance in cell monolayers and increased permeability of the low-molecular-weight markers, mannitol and sucrose; however, permeability of high-molecular-weight markers, polyethylene glycol and inulin, was not affected. In vivo permeability was assessed in male Sprague-Dawley rats treated for 6 days with ethanol, disulfiram, or saline alone or in combination. Bioavailability of naproxen was not affected by any treatment, whereas that of paclitaxel was increased upon acetaldehyde exposure. Although disulfiram has been shown to inhibit multidrug resistance-1 P-glycoprotein (P-gp) in vitro, our data demonstrate that the known P-gp substrate paclitaxel is not affected by coadministration of disulfiram. In conclusion, we demonstrate that acetaldehyde significantly modulates tight junctions and paracellular permeability in vitro as well as the oral bioavailability of low-molecular-weight hydrophilic probes and therapeutic molecules in vivo even when these molecules are substrates for efflux transporters. These studies emphasize the significance of ethanol metabolism and drug interactions outside of the liver.

  1. Liquid and gas phase NMR spectra of 13CH313CHO acetaldehyde

    NASA Astrophysics Data System (ADS)

    Makulski, Włodzimierz; Wikieł, Agata J.

    2018-01-01

    The gas phase NMR experiments perform a vital role in establishing the magnetic shielding and spin-spin coupling constants which are free from intermolecular interactions, equivalent to the parameter of isolated molecules. This work is concerned with an acetaldehyde molecule. Small amounts of acetaldehyde 13CH313CHO in gaseous matrices of CO2 and Xe were studied using high-precision 1H and 13C NMR measurements. Results were extrapolated to the zero-density limit permitting the determinations of the 1H and 13C absolute nuclear magnetic shielding of an isolated acetaldehyde molecule. The difference between the experimental and recent theoretical DFT results is discussed. Several samples of 13CH313CHO dissolved in popular organic and inorganic solvents were also investigated. Gas-to-solution shifts show the influence of the association process when acetaldehyde is transferred from gas to liquid state. Several spin-spin coupling constants in the gas phase and in different solvents were precisely measured.

  2. Inhibition of rat mammary microsomal oxidation of ethanol to acetaldehyde by plant polyphenols.

    PubMed

    Maciel, María Eugenia; Castro, José Alberto; Castro, Gerardo Daniel

    2011-07-01

    We previously reported that the microsomal fraction from rat mammary tissue is able to oxidize ethanol to acetaldehyde, a mutagenic-carcinogenic metabolite, depending on the presence of NADPH and oxygen but not inhibited by carbon monoxide or other cytochrome P450 inhibitors. The process was strongly inhibited by diphenyleneiodonium, a known inhibitor of NADPH oxidase, and by nordihydroguaiaretic acid, an inhibitor of lipoxygenases. This led us to suggest that both enzymes could be involved. With the purpose of identifying natural compounds present in food with the ability to decrease the production of acetaldehyde in mammary tissue, in the present studies, several plant polyphenols having inhibitory effects on lipoxygenases and of antioxidant nature were tested as potential inhibitors of the rat mammary tissue microsomal pathway of ethanol oxidation. We included in the present screening study 32 polyphenols having ready availability and that were also tested against the rat mammary tissue cytosolic metabolism of ethanol to acetaldehyde. Several polyphenols were also able to inhibit the microsomal ethanol oxidation at concentrations as low was 10-50 μM. The results of these screening experiments suggest the potential of several plant polyphenols to prevent in vivo production and accumulation of acetaldehyde in mammary tissue.

  3. Mechanism of acetaldehyde-induced deactivation of microbial lipases

    PubMed Central

    2011-01-01

    Background Microbial lipases represent the most important class of biocatalysts used for a wealth of applications in organic synthesis. An often applied reaction is the lipase-catalyzed transesterification of vinyl esters and alcohols resulting in the formation of acetaldehyde which is known to deactivate microbial lipases, presumably by structural changes caused by initial Schiff-base formation at solvent accessible lysine residues. Previous studies showed that several lipases were sensitive toward acetaldehyde deactivation whereas others were insensitive; however, a general explanation of the acetaldehyde-induced inactivation mechanism is missing. Results Based on five microbial lipases from Candida rugosa, Rhizopus oryzae, Pseudomonas fluorescens and Bacillus subtilis we demonstrate that the protonation state of lysine ε-amino groups is decisive for their sensitivity toward acetaldehyde. Analysis of the diverse modification products of Bacillus subtilis lipases in the presence of acetaldehyde revealed several stable products such as α,β-unsaturated polyenals, which result from base and/or amino acid catalyzed aldol condensation of acetaldehyde. Our studies indicate that these products induce the formation of stable Michael-adducts at solvent-accessible amino acids and thus lead to enzyme deactivation. Further, our results indicate Schiff-base formation with acetaldehyde to be involved in crosslinking of lipase molecules. Conclusions Differences in stability observed with various commercially available microbial lipases most probably result from different purification procedures carried out by the respective manufacturers. We observed that the pH of the buffer used prior to lyophilization of the enzyme sample is of utmost importance. The mechanism of acetaldehyde-induced deactivation of microbial lipases involves the generation of α,β-unsaturated polyenals from acetaldehyde which subsequently form stable Michael-adducts with the enzymes. Lyophilization of

  4. Modeling of experimental treatment of acetaldehyde-laden air and phenol-containing water using corona discharge technique.

    PubMed

    Faungnawakij, Kajornsak; Sano, Noriaki; Charinpanitkul, Tawatchai; Tanthapanichakoon, Wiwut

    2006-03-01

    Acetaldehyde-laden air and phenol-contaminated water were experimentally treated using corona discharge reactions and gas absorption in a single water-film column. Mathematical modeling of the combined treatment was developed in this work. Efficient removal of the gaseous acetaldehyde was achieved while the corona discharge reactions produced short-lived species such as O and O- as well as ozone. Direct contact of the radicals and ions with water was known to produce aqueous OH radical, which contributes to the decomposition of organic contaminants: phenol, absorbed acetaldehyde, and intermediate byproducts in the water. The influence of initial phenol concentration ranging from 15 to 50 mg L(-1) and that of influent acetaldehyde ranging from 0 to 200 ppm were experimentally investigated and used to build the math model. The maximum energetic efficiency of TOC, phenol, and acetaldehyde were obtained at 25.6 x 10(-9) mol carbon J(-1), 25.0 x 10(-9) mol phenol J(-1), and 2.0 x 10(-9) mol acetaldehyde J(-1), respectively. The predictions for the decomposition of acetaldehyde, phenol, and their intermediates were found to be in good agreement with the experimental results.

  5. Replacement of the initial steps of ethanol metabolism in Saccharomyces cerevisiae by ATP-independent acetylating acetaldehyde dehydrogenase

    PubMed Central

    Kozak, Barbara U.; van Rossum, Harmen M.; Niemeijer, Matthijs S.; van Dijk, Marlous; Benjamin, Kirsten; Wu, Liang; Daran, Jean-Marc G.; Pronk, Jack T.

    2016-01-01

    In Saccharomyces cerevisiae ethanol dissimilation is initiated by its oxidation and activation to cytosolic acetyl-CoA. The associated consumption of ATP strongly limits yields of biomass and acetyl-CoA-derived products. Here, we explore the implementation of an ATP-independent pathway for acetyl-CoA synthesis from ethanol that, in theory, enables biomass yield on ethanol that is up to 40% higher. To this end, all native yeast acetaldehyde dehydrogenases (ALDs) were replaced by heterologous acetylating acetaldehyde dehydrogenase (A-ALD). Engineered Ald− strains expressing different A-ALDs did not immediately grow on ethanol, but serial transfer in ethanol-grown batch cultures yielded growth rates of up to 70% of the wild-type value. Mutations in ACS1 were identified in all independently evolved strains and deletion of ACS1 enabled slow growth of non-evolved Ald− A-ALD strains on ethanol. Acquired mutations in A-ALD genes improved affinity—Vmax/Km for acetaldehyde. One of five evolved strains showed a significant 5% increase of its biomass yield in ethanol-limited chemostat cultures. Increased production of acetaldehyde and other by-products was identified as possible cause for lower than theoretically predicted biomass yields. This study proves that the native yeast pathway for conversion of ethanol to acetyl-CoA can be replaced by an engineered pathway with the potential to improve biomass and product yields. PMID:26818854

  6. Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis.

    PubMed

    Hellström, Per M; Hendolin, Panu; Kaihovaara, Pertti; Kronberg, Leif; Meierjohann, Axel; Millerhovf, Anders; Paloheimo, Lea; Sundelin, Heidi; Syrjänen, Kari; Webb, Dominic-Luc; Salaspuro, Mikko

    2017-02-01

    Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

  7. Degradation of Acetaldehyde and Its Precursors by Pelobacter carbinolicus and P. acetylenicus

    PubMed Central

    Schmidt, Alexander; Frensch, Marco; Schleheck, David; Schink, Bernhard; Müller, Nicolai

    2014-01-01

    patterns of both Pelobacter spp. grown with the named substrates were highly similar suggesting that both share the same steps in ethanol and acetalydehyde metabolism. The early assumption that acetaldehyde is a central intermediate in Pelobacter metabolism was now proven biochemically. PMID:25536080

  8. Role of acetaldehyde in ethanol-induced conditioned taste aversion in rats.

    PubMed

    Escarabajal, M Dolores; De Witte, Philippe; Quertemont, Etienne

    2003-05-01

    In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. The present study reexamined the role of acetaldehyde in ethanol-induced conditioned taste aversion (CTA). A first experiment compared ethanol- and acetaldehyde-induced CTA. In a second experiment, cyanamide, an aldehyde dehydrogenase inhibitor, was administered before conditioning with either ethanol or acetaldehyde to investigate the effects of acetaldehyde accumulation. A classic CTA protocol was used to associate the taste of a saccharin solution with either ethanol or acetaldehyde injections. In experiment 1, saccharin consumption was followed by injections of either ethanol (0, 0.5, 1.0, 1.5 or 2.0 g/kg) or acetaldehyde (0, 100, 170 or 300 mg/kg). In experiment 2, the rats were pretreated with either saline or cyanamide (25 mg/kg) before conditioning with either ethanol or acetaldehyde. Both ethanol and acetaldehyde induced significant CTA. However, ethanol produced a very strong CTA relative to acetaldehyde that induced only a weak CTA even at toxic doses. Cyanamide pretreatments significantly potentiated ethanol- but not acetaldehyde-induced CTA. The present results indicate that ethanol-induced CTA does not result from brain acetaldehyde effects. In contrast, it is suggested that the reinforcing effects of brain acetaldehyde might actually reduce ethanol-induced CTA. Our results also suggest that the inhibition of brain catalase activity may contribute to the potentiating effects of cyanamide on ethanol-induced CTA.

  9. Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC-MS

    PubMed Central

    Heit, Claire; Eriksson, Peter; Thompson, David C; Fritz, Kristofer S; Vasiliou, Vasilis

    2016-01-01

    BACKGROUND There is controversy regarding the active agent responsible for alcohol addiction. The theory that ethanol itself was the agent in alcohol drinking behavior was widely accepted until acetaldehyde was found in the brain. The importance of acetaldehyde formation in the brain role is still subject to speculation due to the lack of a method to accurately assay the acetaldehyde levels directly. A highly sensitive GC-MS method to reliably determine acetaldehyde concentration with certainty is needed to address whether neural acetaldehyde is indeed responsible for increased alcohol consumption. METHODS A headspace gas chromatograph coupled to selected ion monitoring mass spectrometry was utilized to develop a quantitative assay for acetaldehyde and ethanol. Our GC-MS approach was carried out using a Bruker Scion 436-GC SQ MS. RESULTS Our approach yields limits of detection of acetaldehyde in the nanomolar range and limits of quantification in the low micromolar range. Our linear calibration includes 5 concentrations with a least square regression greater than 0.99 for both acetaldehyde and ethanol. Tissue analyses using this method revealed the capacity to quantify ethanol and acetaldehyde in blood, brain, and liver tissue from mice. CONCLUSIONS By allowing quantification of very low concentrations, this method may be used to examine the formation of ethanol metabolites, specifically acetaldehyde, in murine brain tissue in alcohol research. PMID:27501276

  10. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

    PubMed Central

    Ceni, Elisabetta; Mello, Tommaso; Galli, Andrea

    2014-01-01

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell

  11. Acetaldehyde-induced structural and conformational alterations in human immunoglobulin G: A physicochemical and multi-spectroscopic study.

    PubMed

    Waris, Sana; Habib, Safia; Tantry, Irfan Qadir; Khan, Rizwan Hasan; Mahmood, Riaz; Ali, Asif

    2018-07-01

    Acetaldehyde is a reactive aldehyde produced as an intermediate of alcohol metabolism and tobacco pyrolysis. It has the potential to interact with different biomolecules in various tissues which results in the formation of stable, unstable and covalent adducts. This causes structural and functional modifications that may lead to severe complications such as cancer. This study has probed the structural modifications in human immunoglobulin G (IgG) as a function of different concentrations of acetaldehyde in the presence of reducing agent, sodium borohydride. Acetaldehyde mediated modifications in IgG have been characterised by various physicochemical techniques. UV-spectrophotometry showed that acetaldehyde modified IgG exhibited marked increase in hyperchromicity. Fluorescence studies revealed a significant quenching of tryptophan fluorescence which resulted in loss of β-sheet secondary structure that was confirmed by circular dichroic analysis. Gross structural changes in the morphology of IgG were confirmed by increase in mass and hydrodynamic radius of this glycoprotein along with the appearance of fibrillar structures in modified IgG, when compared to the granular structure of the native form of IgG observed by scanning electron microscope. The results indicate that acetaldehyde causes alterations in the secondary and tertiary structure of the protein leading to diminution of normal function of IgG molecule. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Quantitative analysis of the lactic acid and acetaldehyde produced by Streptococcus thermophilus and Lactobacillus bulgaricus strains isolated from traditional Turkish yogurts using HPLC.

    PubMed

    Gezginc, Y; Topcal, F; Comertpay, S; Akyol, I

    2015-03-01

    The present study was conducted to evaluate the lactic acid- and acetaldehyde-producing abilities of lactic acid bacterial species isolated from traditionally manufactured Turkish yogurts using HPLC. The lactic acid bacterial species purified from the yogurts were the 2 most widely used species in industrial yogurt production: Streptococcus thermophilus and Lactobacillus bulgaricus. These bacteria have the ability to ferment hexose sugars homofermentatively to generate lactic acid and some carbonyl compounds, such as acetaldehyde through pyruvate metabolism. The levels of the compounds produced during fermentation influence the texture and the flavor of the yogurt and are themselves influenced by the chemical composition of the milk, processing conditions, and the metabolic activity of the starter culture. In the study, morphological, biochemical, and molecular characteristics were employed to identify the bacteria obtained from homemade yogurts produced in different regions of Turkey. A collection of 91 Strep. thermophilus and 35 L. bulgaricus strains were investigated for their lactic acid- and acetaldehyde-formation capabilities in various media such as cow milk, LM17 agar, and aerobic-anaerobic SM17 agar or de Man, Rogosa, and Sharpe agar. The amounts of the metabolites generated by each strain in all conditions were quantified by HPLC. The levels were found to vary depending on the species, the strain, and the growth conditions used. Whereas lactic acid production ranged between 0 and 77.9 mg/kg for Strep. thermophilus strains, it ranged from 0 to 103.5 mg/kg for L. bulgaricus. Correspondingly, the ability to generate acetaldehyde ranged from 0 to 105.9 mg/kg in Strep. thermophilus and from 0 to 126.9 mg/kg in L. bulgaricus. Our study constitutes the first attempt to determine characteristics of the wild strains isolated from traditional Turkish yogurts, and the approach presented here, which reveals the differences in metabolite production abilities of the

  13. Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects

    PubMed Central

    Kocaelli, H; Apaydin, A; Aydil, B; Ayhan, M; Karadeniz, A; Ozel, S; Yılmaz, E; Akgün, B; Eren, B

    2014-01-01

    Background: Acetaldehyde has been implicated as a major factor in oral carcinogenesis associated with alcohol consumption. In this study, saliva samples from oral cancer patients and healthy individuals were incubated in vitro with ethanol in order to investigate factors which can influence salivary acetaldehyde production. Materials and Methods: A total of 66 individuals (40 males and 26 females, mean age 52 years) participated in the study. Participants were classified into three groups: Group 1 (oral cancer patients [n = 20]); Group 2 (poor dental health status [n = 25]) and Group 3 (good dental health status [n=21]). Every patient chewed a 1g piece of paraffin chewing gum for 1 minute then saliva samples were collected from all individuals. After in vitro incubation of the samples with ethanol, the levels of salivary acetaldehyde production was measured by head space gas chromatography. Kruskal-Wallis and Mann-Whitney tests and Spearman's Correlations analysis were performed for statistical analyses. Results: The salivary acetaldehyde production was significantly higher (p <0.0001) in both group 1 and group 2 when compared to group 3. However, there was no significant difference between group 1 and group 2. Poor dental health status, infrequent oral hygiene habits and dental visits, smoking and presence of a dental prosthesis were significant parameters for increased levels of salivary acetaldehyde production from alcohol. The evaluation of salivary acetaldehyde production after in vitro incubation with ethanol may be useful for early detection of oral cancer. Conclusion: According to the results of this study, the significantly higher levels of salivary acetaldehyde production in oral cancer patients and individuals with poor dental health status may suggest a possible link between increased salivary acetaldehyde production and oral cancer. Improved oral hygiene can effectively decrease the level of salivary acetaldehyde production in oral cavity. Hippokratia

  14. Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects.

    PubMed

    Kocaelli, H; Apaydin, A; Aydil, B; Ayhan, M; Karadeniz, A; Ozel, S; Yılmaz, E; Akgün, B; Eren, B

    2014-01-01

    Acetaldehyde has been implicated as a major factor in oral carcinogenesis associated with alcohol consumption. In this study, saliva samples from oral cancer patients and healthy individuals were incubated in vitro with ethanol in order to investigate factors which can influence salivary acetaldehyde production. A total of 66 individuals (40 males and 26 females, mean age 52 years) participated in the study. Participants were classified into three groups: Group 1 (oral cancer patients [n = 20]); Group 2 (poor dental health status [n = 25]) and Group 3 (good dental health status [n=21]). Every patient chewed a 1g piece of paraffin chewing gum for 1 minute then saliva samples were collected from all individuals. After in vitro incubation of the samples with ethanol, the levels of salivary acetaldehyde production was measured by head space gas chromatography. Kruskal-Wallis and Mann-Whitney tests and Spearman's Correlations analysis were performed for statistical analyses. The salivary acetaldehyde production was significantly higher (p <0.0001) in both group 1 and group 2 when compared to group 3. However, there was no significant difference between group 1 and group 2. Poor dental health status, infrequent oral hygiene habits and dental visits, smoking and presence of a dental prosthesis were significant parameters for increased levels of salivary acetaldehyde production from alcohol. The evaluation of salivary acetaldehyde production after in vitro incubation with ethanol may be useful for early detection of oral cancer. According to the results of this study, the significantly higher levels of salivary acetaldehyde production in oral cancer patients and individuals with poor dental health status may suggest a possible link between increased salivary acetaldehyde production and oral cancer. Improved oral hygiene can effectively decrease the level of salivary acetaldehyde production in oral cavity. Hippokratia 2014; 18 (3): 269-274.

  15. ANTABUS AND THE METABOLISM OF ALCOHOL

    PubMed Central

    Newman, Henry W.

    1950-01-01

    Antabus does not alter the rate of alcohol metabolism in dogs. It interferes with the metabolism of acetaldehyde, so that the ordinarily prompt removal of this substance from the tissues as it is produced in the metabolism of alcohol does not take place. It seems reasonable to assume that it is this accumulation of acetaldehyde in the tissues in abnormally high concentrations that is responsible for the unpleasant symptoms following the taking of alcohol by a patient receiving antabus. PMID:15426985

  16. Metabolic regulation and maximal reaction optimization in the central metabolism of a yeast cell

    NASA Astrophysics Data System (ADS)

    Kasbawati, Gunawan, A. Y.; Hertadi, R.; Sidarto, K. A.

    2015-03-01

    Regulation of fluxes in a metabolic system aims to enhance the production rates of biotechnologically important compounds. Regulation is held via modification the cellular activities of a metabolic system. In this study, we present a metabolic analysis of ethanol fermentation process of a yeast cell in terms of continuous culture scheme. The metabolic regulation is based on the kinetic formulation in combination with metabolic control analysis to indicate the key enzymes which can be modified to enhance ethanol production. The model is used to calculate the intracellular fluxes in the central metabolism of the yeast cell. Optimal control is then applied to the kinetic model to find the optimal regulation for the fermentation system. The sensitivity results show that there are external and internal control parameters which are adjusted in enhancing ethanol production. As an external control parameter, glucose supply should be chosen in appropriate way such that the optimal ethanol production can be achieved. For the internal control parameter, we find three enzymes as regulation targets namely acetaldehyde dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase which reside in the acetaldehyde branch. Among the three enzymes, however, only acetaldehyde dehydrogenase has a significant effect to obtain optimal ethanol production efficiently.

  17. Prebiotic synthesis of imidazole-4-acetaldehyde and histidine

    NASA Astrophysics Data System (ADS)

    Shen, Chun; Yang, Lily; Miller, Stanley L.; Oró, J.

    1987-09-01

    The prebiotic synthesis of imidazole-4-acetaldehyde and imidazole-4-glycol from erythrose and formamidine has been demonstrated as well as the prebiotic synthesis of imidazole-4-ethanol and imidazole-4-glycol from erythrose, formaldehyde and ammonia. The products were identified by TLC, HPLC, and LC-MS by comparison with authentic samples. The maximum yields of imidazole-4-acetaldehyde, imidazole-4-ethanol, and imidazole-4-glycol obtained in these reactions are 1.6, 5.4, 6.8% respectively, based on the erythrose. Imidazole-4-acetaldehyde would have been converted to histidine on the primitive earth by a Strecker synthesis, and several prebiotic reactions would convert imidazole-4-glycol and imidazole-4-ethanol to imidazole-4-acetaldehyde.

  18. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    PubMed

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  19. Relationship between acetaldehyde concentration in mouth air and tongue coating volume.

    PubMed

    Yokoi, Aya; Maruyama, Takayuki; Yamanaka, Reiko; Ekuni, Daisuke; Tomofuji, Takaaki; Kashiwazaki, Haruhiko; Yamazaki, Yutaka; Morita, Manabu

    2015-01-01

    Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume.

  20. Relationship between acetaldehyde concentration in mouth air and tongue coating volume

    PubMed Central

    YOKOI, Aya; MARUYAMA, Takayuki; YAMANAKA, Reiko; EKUNI, Daisuke; TOMOFUJI, Takaaki; KASHIWAZAKI, Haruhiko; YAMAZAKI, Yutaka; MORITA, Manabu

    2015-01-01

    Objective Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Material and Methods Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Results Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Conclusion Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume. PMID:25760268

  1. Research on alcohol metabolism among Asians and its implications for understanding causes of alcoholism.

    PubMed Central

    Suddendorf, R F

    1989-01-01

    Research into the causes of alcoholism is a relatively recent scientific endeavor. One area of study which could lead to better understanding of the disease is the possibility of a genetic predisposition to alcoholism. Recent work has demonstrated that people have varying complements of enzymes to metabolize alcohol. Current knowledge is examined about the influence of various ethanol metabolizing enzymes on alcohol consumption by Asians and members of other ethnic groups. The two principal enzymes involved in ethanol oxidative metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH is responsible for the metabolism of ethanol to acetaldehyde. ALDH catalyzes the conversion of acetaldehyde to acetate. The different isozymes account for the diversity of alcohol metabolism among individuals. An isozyme of ADH (beta 2 beta 2) is found more frequently in Asians than in whites, and an ALDH isozyme (ALDH2), although present in Asians, often is in an inactive form. The presence of an inactive form of ALDH2 is thought to be responsible for an increase in acetaldehyde levels in the body. Acetaldehyde is considered responsible for the facial flushing reaction often observed among Asians who have consumed alcohol. A dysphoric reaction to alcohol, producing uncomfortable sensations, is believed to be a response to deter further consumption. Although the presence of an inactive ALDH2 isozyme may serve as a deterrent to alcohol consumption, its presence does not fully explain the levels of alcohol consumption by those with the inactive isozyme. Other conditions, such as social pressure, and yet undetermined biological factors, may play a significant role in alcohol consumption. PMID:2511595

  2. Simultaneous determination of diethylacetal and acetaldehyde during beer fermentation and storage process.

    PubMed

    Liu, Chunfeng; Li, Qi; Niu, Chengtuo; Zheng, Feiyun; Zhao, Yun

    2018-03-15

    Acetaldehyde is an important flavor component in beer, which is possibly carcinogenic to humans. Due to the limit of present detect methods, only the free-state acetaldehyde in beers was focused on, but the acetal in beers had been hardly reported so far. A sensitive HS-GC method was developed for the determination of diethylacetal and acetaldehyde in beer. The column DB-23 was chosen with a total run time of 22.5 min. The optimal addition amount of NaCl, equilibrium temperature and time were 2.0 g, 70 °C, and 30 min. Both for diethylacetal and acetaldehyde analysis, the LOD was 0.005 mg/L with RSD<5.5 %. The recoveries of acetaldehyde and diethylacetal were 95-110% and 95-115%. The diethylacetal and acetaldehyde average content in 24 beer products were 11.83 mg/L and 4.36 mg/L, respectively. Pearson correlation coefficient between diethylacetal and acetaldehyde was the highest (0.963). Both of diethylacetal and acetaldehyde content increased to a peak value when fermentation for 3 days, and then decreased to a lower value. Both during the normal storage and forcing aging process, the diethylacetal content decreased and the acetaldehyde content increased gradually with time extending. When beers were forced aging for 4 days, the increased ratio of acetaldehyde could be above 40.00%. The newly established method can be used to assess acetaldehyde level and flavor quality in beer more scientifically. This article is protected by copyright. All rights reserved.

  3. Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men.

    PubMed

    Yokoyama, Akira; Tsutsumi, Eri; Imazeki, Hiromi; Suwa, Yoshihide; Nakamura, Chizu; Yokoyama, Tetsuji

    2010-07-01

    The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner

  4. Reaction of Acetaldehyde with Wine Flavonoids in the Presence of Sulfur Dioxide.

    PubMed

    Sheridan, Marlena K; Elias, Ryan J

    2016-11-16

    Acetaldehyde is responsible for many of the beneficial changes that occur in red wine as a result of oxidation. Ethylidene bridges are formed between flavonoids upon their reaction with acetaldehyde, which can contribute to improvements in color stability and SO 2 -resistant pigments. In the present study, the reactions between acetaldehyde and various flavonoids (catechin, tannins from grape seed extract, and malvidin-3-glucoside) were examined in a model wine system. Lower pH conditions were seen to significantly increase the rate of reaction with acetaldehyde, whereas dissolved oxygen did not affect the rate. In systems containing SO 2 , the rate of reaction of acetaldehyde with catechin was slowed but was not prevented until SO 2 was in great excess. Significant improvements in color stability were also observed after treatment with acetaldehyde, despite the presence of equimolar SO 2 . These results demonstrate that acetaldehyde is reactive in its sulfonate form, which is contrary to widely held assumptions. In addition, the products of the reaction of flavonoids with acetaldehyde were characterized using MALDI-TOF MS in this study. Ethyl-bridged catechin nonamers were observed, as well as anthocyanin and pyranoanthocyanin derivatives of catechin and tannin oligomers. The results of this work illustrate the significance of acetaldehyde reactions in forming stable pigments in wine and the reactivity of acetaldehyde from its sulfonate form.

  5. Heterogeneous Interactions of Acetaldehyde and Sulfuric Acid

    NASA Technical Reports Server (NTRS)

    Michelsen, R. R.; Ashbourn, S. F. M.; Iraci, L. T.

    2004-01-01

    The uptake of acetaldehyde [CH3CHO] by aqueous sulfuric acid has been studied via Knudsen cell experiments over ranges of temperature (210-250 K) and acid concentration (40-80 wt. %) representative of the upper troposphere. The Henry's law constants for acetaldehyde calculated from these data range from 6 x 10(exp 2) M/atm for 40 wt. % H2SO4 at 228 K to 2 x 10(exp 5) M/atm for 80 wt. % H2SO4 at 212 K. In some instances, acetaldehyde uptake exhibits apparent steady-state loss. The possible sources of this behavior, including polymerization, will be explored. Furthermore, the implications for heterogeneous reactions of aldehydes in sulfate aerosols in the upper troposphere will be discussed.

  6. Involvement of dopamine D2 receptors in addictive-like behaviour for acetaldehyde.

    PubMed

    Brancato, Anna; Plescia, Fulvio; Marino, Rosa Anna Maria; Maniaci, Giuseppe; Navarra, Michele; Cannizzaro, Carla

    2014-01-01

    Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further strengthen the evidence

  7. 40 CFR 721.10036 - Acetaldehyde based polymer (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

  8. 40 CFR 721.10036 - Acetaldehyde based polymer (generic).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

  9. 40 CFR 721.10036 - Acetaldehyde based polymer (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

  10. 40 CFR 721.10036 - Acetaldehyde based polymer (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

  11. 40 CFR 721.10036 - Acetaldehyde based polymer (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

  12. Phytotoxicity of citrus and subtropical fruits to acetaldehyde vapor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prasad, K.

    1975-01-01

    Several citrus and subtropical fruits (oranges, limes, lemons, mangos and papayas) were evaluated for phytotoxicity to acetaldehyde vapor. Exposure of fruits to 0.5 or 1% acetaldehyde vapor for 24 hr (low concentration-long exposure) did not produce skin injury or off-flavor in comparison with non-exposed fruits. This non-phytotoxic effect was also obtained at 5 to 20% acetaldehyde vapor for 10 to 15 min (high concentration-short exposure). However, acetaldehyde vapor concentration of 4% for 1 hr or 5% for 30 min (high concentration-long exposure) produced severe lenticel and skin injuries to the fruits. Exposure of fruits at these concentration also produced lackmore » of or off-flavor. Phytotoxicity of fruits to acetaldhyde vapor was a function of concentration and exposure.« less

  13. Development of an LC-MS/MS method for studying migration characteristics of acetaldehyde in polyethylene terephthalate (PET)-packed mineral water.

    PubMed

    Baumjohann, Nina; Harms, Diedrich

    2015-01-01

    During storage, acetaldehyde migration from polyethylene terephthalate (PET) bottles can affect the quality of mineral water even in the low µg l(-1) range negatively, as it features a fruity or plastic-like off-flavour. For a sensitive and fast analysis of acetaldehyde in mineral water, a new analysis method of 2,4-dinitrophenylhydrazine (DNPH) derivatisation followed by HPLC-electrospray tandem mass spectrometry (ESI-MS/MS) was developed. Acetaldehyde was directly derivatised in the mineral water sample avoiding extraction and/or pre-concentration steps and then analysed by reversed-phase HPLC-ESI-MS/MS using multiple reaction monitoring mode (MRM). Along with method development, the optimum molar excess of DNPH in contrast to acetaldehyde was studied for the mineral water matrix, because no specific and robust data were yet available for this critical parameter. Best results were obtained by using a calibration via the derivatisation reaction. Without any analyte enrichment or extraction, an LOD of 0.5 µg l(-1) and an LOQ of 1.9 µg l(-1) were achieved. Using the developed method, mineral water samples packed in PET bottles from Germany were analysed and the correlation between the acetaldehyde concentration and other characteristics of the samples was evaluated illustrating the applicability of the method. Besides a relationship between bottle size and CO2 content of the mineral water and acetaldehyde migration, a correlation with acetaldehyde migration and the material composition of the bottle, e.g. recycled PET, was noted. Investigating the light influence on the acetaldehyde migration with a newly developed, reproducible light exposure setup, a significant increase of the acetaldehyde concentration in carbonated mineral water samples was observed.

  14. Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

    PubMed

    Fan, Fan; Cao, Quan; Wang, Cong; Ma, Xin; Shen, Cheng; Liu, Xiang-wei; Bu, Li-ping; Zou, Yun-zeng; Hu, Kai; Sun, Ai-jun; Ge, Jun-bo

    2014-08-01

    To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

  15. Acetone and Acetaldehyde Exchange Above a Managed Temperate Mountain Grassland

    NASA Astrophysics Data System (ADS)

    Hörtnagl, L. J.; Bamberger, I.; Graus, M.; Ruuskanen, T.; Schnitzhofer, R.; Hansel, A.; Wohlfahrt, G.

    2011-12-01

    measurement campaigns and during undisturbed conditions. The shortcomings in predicting VOC fluxes might be a consequence of missing parameters that were not captured by our meteorological data. The identification and quantification of biochemical cycles associated with soil and plant root processes and the possible influence of insect life cycles on VOC exchange might provide important information during the development and parameterization of VOC models. The total amount of carbon associated with the VOC flux of the two compounds was low: the grassland was a net source of acetaldehyde in both years with emissions of 21.8 mg C m-2 and 10.2 mg C m-2 in 2008 and 2009, respectively, while the meadow was a source of acetone in 2008 with 14.6 mg C m-2 and a sink in 2009 with a cumulative uptake of 5.0 mg C m-2.

  16. Modelling bidirectional fluxes of methanol and acetaldehyde with the FORCAsT canopy exchange model

    DOE PAGES

    Ashworth, Kirsti; Chung, Serena H.; McKinney, Karena A.; ...

    2016-12-15

    Here, the FORCAsT canopy exchange model was used to investigate the underlying mechanisms governing foliage emissions of methanol and acetaldehyde, two short chain oxygenated volatile organic compounds ubiquitous in the troposphere and known to have strong biogenic sources, at a northern mid-latitude forest site. The explicit representation of the vegetation canopy within the model allowed us to test the hypothesis that stomatal conductance regulates emissions of these compounds to an extent that its influence is observable at the ecosystem scale, a process not currently considered in regional- or global-scale atmospheric chemistry models. Here, we found that FORCAsT could only reproducemore » the magnitude and diurnal profiles of methanol and acetaldehyde fluxes measured at the top of the forest canopy at Harvard Forest if light-dependent emissions were introduced to the model. With the inclusion of such emissions, FORCAsT was able to successfully simulate the observed bidirectional exchange of methanol and acetaldehyde. Although we found evidence that stomatal conductance influences methanol fluxes and concentrations at scales beyond the leaf level, particularly at dawn and dusk, we were able to adequately capture ecosystem exchange without the addition of stomatal control to the standard parameterisations of foliage emissions, suggesting that ecosystem fluxes can be well enough represented by the emissions models currently used.« less

  17. [Usefulness of the fruit fly for assessment of mutagenicity of benzene, acetaldehyde and formaldehyde].

    PubMed

    Krogulski, A

    1994-01-01

    Among the contaminants of water, soil and air the number of mutagenic and carcinogenic substances is increasing. For the assessment of health risk connected with the simple and cheap methods are necessary which could detected and measure the mutagenicity of these substances. The widely used tests using prokaryotes give negative results in the tests of certain substances which are carcinogenic in mammals. In the case of benzene and acetaldehyde Ames test gives false negative results, and in the case of formaldehyde the results are equivocal. An advantage of fruit fly Drosophila melanogaster used for this purpose is that its cell structures, enzymes and metabolic processes are similar to those of mammals. For the demonstration of mutagenicity of benzene, acetaldehyde and formaldehyde the test of somatic mutation and recombination SMART was carried out in these flies. The results confirmed the usefulness of the SMART test for the demonstration of the mutagenicity of contaminants in the environment.

  18. Disulfiram treatment increases plasma and red blood cell acetaldehyde in abstinent alcoholics.

    PubMed

    Rosman, A S; Waraich, A; Baraona, E; Lieber, C S

    2000-07-01

    Much of alcohol's toxicity is due to its product, acetaldehyde. The role of acetaldehyde derived from endogenous sources was assessed in alcoholic patients administered disulfiram, an inhibitor of aldehyde dehydrogenase. The first part of the study included 23 subjects without biochemical or clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11 patients were started on disulfiram (250 mg/day), whereas the other 12 were not given disulfiram and served as controls. The second part of the study included 13 alcoholic patients with clinical or pathological evidence of cirrhosis who also were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC) acetaldehyde as well as serum transaminases were measured at baseline and after 1 and 2 weeks of treatment. In the disulfiram-treated group of alcoholics without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26 microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1 week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram treatment (p < 0.001). There were no significant differences in sequential levels measured in either plasma or RBC acetaldehyde levels in patients who were not administered disulfiram. In the group of cirrhotic patients, the mean baseline RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p < 0.05). Compared with baseline values, plasma acetaldehyde levels were significantly higher after 1 week but not after 2 weeks of disulfiram. There were no significant differences among serum transaminases in alcoholics administered disulfiram, although three cirrhotic patients did have

  19. The hydrogen-storing microporous silica 'Microcluster' reduces acetaldehyde contained in a distilled spirit.

    PubMed

    Kato, Shinya; Miwa, Nobuhiko

    2016-12-01

    Acetaldehyde is a detrimental substance produced in alcoholic liquor aging. We assessed an ability of hydrogen-storing microporous silica 'Microcluster' (MC+) to reduce acetaldehyde, as compared with autoclave-dehydrogenated MC+ (MC-). Acetaldehyde was quantified spectrophotometrically by an enzymatic method. Authentic acetaldehyde was treated by MC+ for 20min, and decreased from 43.4ppm to 10.9ppm, but maintained at 49.3ppm by MC-. On the other hand, acetaldehyde contained in a distilled spirit was decreased from 29.5ppm to 3.1ppm at 20min by MC+, but not decreased by MC-. Addition of MC+ or MC- to distilled water without acetaldehyde showed no seeming effect on the quantification used. Accordingly acetaldehyde in a distilled spirit is reduced to ethanol by hydrogen contained in MC+, but not by the silica moiety of MC+. Hydrogen gas of 1.2mL was released for 20min from MC+ of 0.59g in water, resulting in dissolved hydrogen of 1.09ppm and an oxidation- reduction potential of -687.0mV indicative of a marked reducing ability. Thus, MC+ has an ability to reduce acetaldehyde in a distilled spirit due to dissolved hydrogen released from MC+. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Comprehensive Study of the Evolution of the Gas-Liquid Partitioning of Acetaldehyde during Wine Alcoholic Fermentation.

    PubMed

    Aguera, Evelyne; Sire, Yannick; Mouret, Jean-Roch; Sablayrolles, Jean-Marie; Farines, Vincent

    2018-06-20

    Determining the gas-liquid partitioning ( K i ) of acetaldehyde during alcoholic fermentation is an important step in the optimization of fermentation control with the aim of minimizing the accumulation of this compound, which is responsible for the undesired attributes of green apples and fresh-cut grass in wines. In this work, the effects of the main fermentation parameters on the K i of acetaldehyde were assessed. K i values were found to be dependent on the temperature and composition of the medium. A nonlinear correlation between the evolution of the K i and fermentation progress was observed, attributable to the strong retention effect of ethanol at low concentrations, and it was demonstrated that the partitioning of this specific molecule was not influenced by the CO 2 production rate. A model was developed that quantifies the K i of acetaldehyde with a very accurate prediction, as the difference between the observed and predicted values did not exceed 9%.

  1. Exogenous acetaldehyde as a tool for modulating wine color and astringency during fermentation.

    PubMed

    Sheridan, Marlena K; Elias, Ryan J

    2015-06-15

    Wine tannins undergo modifications during fermentation and storage that can decrease their perceived astringency and increase color stability. Acetaldehyde acts as a bridging compound to form modified tannins and polymeric pigments that are less likely to form tannin-protein complexes than unmodified tannins. Red wines are often treated with oxygen in order to yield acetaldehyde, however this approach can lead to unintended consequences due to the generation of reactive oxygen species. The present study employs exogenous acetaldehyde at relatively low and high treatment concentrations during fermentation to encourage tannin modification without promoting potentially deleterious oxidation reactions. The high acetaldehyde treatment significantly increased polymeric pigments in the wine without increasing concentrations of free and sulfite-bound acetaldehyde. Protein-tannin precipitation was also significantly decreased with the addition of exogenous acetaldehyde. These results indicate a possible treatment of wines early in their production to increase color stability and lower astringency of finished wines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. An original method for producing acetaldehyde and diacetyl by yeast fermentation.

    PubMed

    Rosca, Irina; Petrovici, Anca Roxana; Brebu, Mihai; Stoica, Irina; Minea, Bogdan; Marangoci, Narcisa

    In this study a natural culture medium that mimics the synthetic yeast peptone glucose medium used for yeast fermentations was designed to screen and select yeasts capable of producing high levels of diacetyl and acetaldehyde. The presence of whey powder and sodium citrate in the medium along with manganese and magnesium sulfate enhanced both biomass and aroma development. A total of 52 yeasts strains were cultivated in two different culture media, namely, yeast peptone glucose medium and yeast acetaldehyde-diacetyl medium. The initial screening of the strains was based on the qualitative reaction of the acetaldehyde with Schiff's reagent (violet color) and diacetyl with Brady's reagent (yellow precipitate). The fermented culture media of 10 yeast strains were subsequently analyzed by gas chromatography to quantify the concentration of acetaldehyde and diacetyl synthesized. Total titratable acidity values indicated that a total titratable acidity of 5.5°SH, implying culture medium at basic pH, was more favorable for the acetaldehyde biosynthesis using strain D15 (Candida lipolytica; 96.05mgL -1 acetaldehyde) while a total titratable acidity value of 7°SH facilitated diacetyl flavor synthesis by strain D38 (Candida globosa; 3.58mgL -1 diacetyl). Importantly, the results presented here suggest that this can be potentially used in the baking industry. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  3. Acetaldehyde Adsorption and Reaction onCeO2(100) Thin Films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mullins, David R; Albrecht, Peter M

    2013-01-01

    This study reports and compares the adsorption and dissociation of acetaldehyde on oxidized and reduced CeOX(100) thin films. Acetaldehyde reacts and decomposes on fully oxidized CeO2(100) whereas it desorbs molecularly at low temperature on CeO2(111). The primary products are CO, CO2 and water along with trace amounts of crotonaldehyde and acetylene. The acetaldehyde adsorbs as the 2-acetaldehyde species, dioxyethylene. Decomposition proceeds by dehydrogenation through acetate and enolate intermediates. The reaction pathway is similar on the reduced CeO2-X(100) surface however the inability to react with surface O on the reduced surface results in H2 rather than H2O desorption and C ismore » left on the surface rather than producing CO and CO2. C-O bond cleavage in the enolate intermediate followed by reaction with surface H results in ethylene desorption.« less

  4. Acetaldehyde production and microbial colonization in oral squamous cell carcinoma and oral lichenoid disease.

    PubMed

    Marttila, Emilia; Uittamo, Johanna; Rusanen, Peter; Lindqvist, Christian; Salaspuro, Mikko; Rautemaa, Riina

    2013-07-01

    The main aim of this prospective study was to explore the ability of the oral microbiome to produce acetaldehyde in ethanol incubation. A total of 90 patients [30 oral squamous cell carcinoma (OSCC); 30 oral lichenoid disease (OLD); 30 healthy controls (CO)] were enrolled in the study. Microbial samples were taken from the mucosa using a filter paper method. The density of microbial colonization was calculated and the spectrum analyzed. Microbial acetaldehyde production was measured by gas chromatography. The majority (68%) of cultures produced carcinogenic levels of acetaldehyde (>100 μM) when incubated with ethanol (22 mM). The mean acetaldehyde production by microbes cultured from smoker samples was significantly higher (213 μM) than from non-smoker samples (141 μM) (P=.0326). The oral microbiota from OSCC, OLD patients and healthy individuals are able to produce carcinogenic levels of acetaldehyde. The present provisional study suggests smoking may increase the production of acetaldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Measurements of formaldehyde and acetaldehyde in the urban ambient air

    NASA Astrophysics Data System (ADS)

    Salas, Louis J.; Singh, Hanwant B.

    Acetaldehyde and formaldehyde were measured in urban ambient air by analyzing their 2,4-dinitrophenylhydrazine derivatives with reverse-phase, high-performance liquid chromatography (HPLC). A series of nine short term field experiments were performed in eight cities. Concurrent formaldehyde measurements using the chromotropic-acid procedure show reasonable agreement (±30 %) between the two methods. Average summertime ambient urban formaldehyde (HCHO) concentrations of 10-20 ppb (10 -9v/v) are significantly higher than the average acetaldehyde (CH 3CHO) concentrations of 1-2 ppb. There is evidence of much reduced formaldehyde levels in winter months. Exceptionally high, absolute (8.5 ppb av.) and relative ( HCHO/CH 3CHO ~ 2 ) acetaldehyde concentrations are measured in the South Coast Air Basin of California.

  6. Quality Characteristics and Quantification of Acetaldehyde and Methanol in Apple Wine Fermentation by Various Pre-Treatments of Mash

    PubMed Central

    Won, Seon Yi; Seo, Jae Soon; Kwak, Han Sub; Lee, Youngseung; Kim, Misook; Shim, Hyoung-Seok; Jeong, Yoonhwa

    2015-01-01

    The objective of this study was to compare the effects of adding lactic acid and pectinase, and chaptalization for the quality of apple wine and the production of hazardous compounds (methanol and acetaldehyde). The pH of all of the samples was below 4; therefore, mash seemed to be fermented without any issue. Total acidity was the highest in sample A due to lactic acid addition. Pre-treated groups (samples B, C, and D) showed higher total acidities than that of the control (P<0.05). Pre-treatments might influence the production of organic acids in apple wines. The control and pectinase added sample (sample B) had the lowest alcohol contents. Adding lactic acid produced more alcohol, and chaptalized samples produced more alcohol due to the addition of sugar. Adding pectinase with and without chaptalization was not effective for producing more alcohol. The control sample had significantly higher acetaldehyde content (2.39 mg/L) than the other samples (1.00~2.07 mg/L); therefore, pre-treatments for apple wine fermentation produced a lower amount of acetaldehyde. Among the pre-treated samples, samples C and D showed the lowest acetaldehyde content of 1.00 mg/L and 1.16 mg/L, respectively. On the other hand, a significantly higher amount of methanol was generated for sample A (1.03 mg/L) and sample D (1.22 mg/L) than that of the control (0.82 mg/L) (P<0.05). Adding lactic acid or chaptalization was effective in reducing methanol and acetaldehyde in apple wines. PMID:26770917

  7. Determination of 14C/ 12C of acetaldehyde in indoor air by compound specific radiocarbon analysis

    NASA Astrophysics Data System (ADS)

    Kato, Yoshimi; Shinohara, Naohide; Yoshinaga, Jun; Uchida, Masao; Matsuda, Ayuri; Yoneda, Minoru; Shibata, Yasuyuki

    A method of compound-specific radiocarbon analysis (CSRA) for acetaldehyde in indoor air was established for the source apportionment purpose and the methodology was applied to indoor air samples. Acetaldehyde in indoor air samples was collected using the conventional 2,4-dinitrophenylhydrazine (DNPH) derivatization method. Typically 24-h air sampling at 5-10 L min -1 allowed collection of adequate amount of acetaldehyde for radiocarbon analysis by accelerator mass spectrometry (AMS). The 14C abundance of acetaldehyde in indoor air was measured by AMS after solvent extraction of derivatized acetaldehyde and sequential purification by a preparative liquid chromatography system and a preparative capillary gas chromatography system. The recovery and purity of the derivatized acetaldehyde was satisfactory for 14C analysis by AMS. 14C abundance of acetaldehyde was calculated by considering that of derivatizing agent DNPH. Our preliminary survey showed that percent modern carbon (pMC) values of acetaldehyde isolated from indoor air sampled in newly built, unoccupied housings ( n=5) in the suburb of Tokyo ranged from 49.4 to 67.0. This result indicated that contribution of anthropogenic source was greater than previously expected.

  8. Dissociative electron attachments to ethanol and acetaldehyde: A combined experimental and simulation study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Xu-Dong; Xuan, Chuan-Jin; Feng, Wen-Ling

    Dissociation dynamics of the temporary negative ions of ethanol and acetaldehyde formed by the low-energy electron attachments is investigated by using the anion velocity map imaging technique and ab initio molecular dynamics simulations. The momentum images of the dominant fragments O{sup −}/OH{sup −} and CH{sub 3}{sup −} are recorded, indicating the low kinetic energies of O{sup −}/OH{sup −} for ethanol while the low and high kinetic energy distributions of O{sup −} ions for acetaldehyde. The CH{sub 3}{sup −} image for acetaldehyde also shows the low kinetic energy. With help of the dynamics simulations, the fragmentation processes are qualitatively clarified. Amore » new cascade dissociation pathway to produce the slow O{sup −} ion via the dehydrogenated intermediate, CH{sub 3}CHO{sup −} (acetaldehyde anion), is proposed for the dissociative electron attachment to ethanol. After the electron attachment to acetaldehyde molecule, the slow CH{sub 3}{sup −} is produced quickly in the two-body dissociation with the internal energy redistributions in different aspects before bond cleavages.« less

  9. Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake.

    PubMed

    Okata, Hideki; Hatta, Waku; Iijima, Katsunori; Asanuma, Kiyotaka; Tsuruya, Atsuki; Asano, Naoki; Koike, Tomoyuki; Hamada, Shin; Nakayama, Toru; Masamune, Atsushi; Shimosegawa, Tooru

    2018-04-01

    Ethanol is oxidized by alcohol dehydrogenase to acetaldehyde, a recognized carcinogen for the esophagus. However, no previous study has measured the acetaldehyde levels in the esophageal tissue. L-cysteine has been shown to reduce the acetaldehyde levels in the saliva; however, it is unknown whether L-cysteine intake affects the acetaldehyde concentration in the esophageal tissue. The aim of this study was to measure the acetaldehyde concentration in the esophageal tissue after ethanol drinking and evaluate the effect of L-cysteine intake on the acetaldehyde levels in the esophagus. We enrolled 10 male subjects with active acetaldehyde dehydrogenase-2*1/*1 (ALDH2*1/*1) genotype and 10 male subjects with the inactive acetaldehyde dehydrogenase-2*1/*2 (ALDH2*1/*2) genotype, the mean ages of whom were 25.6 and 27.9 years, respectively. In this prospective, single-blind, placebo-controlled study using L-cysteine and placebo lozenges (first and second examination), saliva and blood were collected before and after ethanol drinking. Esophageal tissue was obtained by endoscopic biopsy at 60 minutes after drinking, and the acetaldehyde and ethanol concentrations were measured. The acetaldehyde concentration of the saliva was significantly lower in those taking L-cysteine than in those taking the placebo. Acetaldehyde in the esophageal tissue was detected only in those taking L-cysteine lozenges. There were no correlations between the acetaldehyde concentrations in the esophageal tissue and saliva or blood. In conclusion, we detected acetaldehyde in the human esophageal tissue after ethanol drinking. Unexpectedly, intake of L-cysteine lozenges appears to contribute to detection of acetaldehyde in the esophageal tissue.

  10. Paracoccus denitrificans PD1222 Utilizes Hypotaurine via Transamination Followed by Spontaneous Desulfination To Yield Acetaldehyde and, Finally, Acetate for Growth

    PubMed Central

    Felux, Ann-Katrin; Denger, Karin; Weiss, Michael; Cook, Alasdair M.

    2013-01-01

    Hypotaurine (HT; 2-aminoethane-sulfinate) is known to be utilized by bacteria as a sole source of carbon, nitrogen, and energy for growth, as is taurine (2-aminoethane-sulfonate); however, the corresponding HT degradation pathway has remained undefined. Genome-sequenced Paracoccus denitrificans PD1222 utilized HT (and taurine) quantitatively for heterotrophic growth and released the HT sulfur as sulfite (and sulfate) and HT nitrogen as ammonium. Enzyme assays with cell extracts suggested that an HT-inducible HT:pyruvate aminotransferase (Hpa) catalyzes the deamination of HT in an initial reaction step. Partial purification of the Hpa activity and peptide fingerprinting-mass spectrometry (PF-MS) identified the Hpa candidate gene; it encoded an archetypal taurine:pyruvate aminotransferase (Tpa). The same gene product was identified via differential PAGE and PF-MS, as was the gene of a strongly HT-inducible aldehyde dehydrogenase (Adh). Both genes were overexpressed in Escherichia coli. The overexpressed, purified Hpa/Tpa showed HT:pyruvate-aminotransferase activity. Alanine, acetaldehyde, and sulfite were identified as the reaction products but not sulfinoacetaldehyde; the reaction of Hpa/Tpa with taurine yielded sulfoacetaldehyde, which is stable. The overexpressed, purified Adh oxidized the acetaldehyde generated during the Hpa reaction to acetate in an NAD+-dependent reaction. Based on these results, the following degradation pathway for HT in strain PD1222 can be depicted. The identified aminotransferase converts HT to sulfinoacetaldehyde, which desulfinates spontaneously to acetaldehyde and sulfite; the inducible aldehyde dehydrogenase oxidizes acetaldehyde to yield acetate, which is metabolized, and sulfite, which is excreted. PMID:23603744

  11. A single sip of a strong alcoholic beverage causes exposure to carcinogenic concentrations of acetaldehyde in the oral cavity.

    PubMed

    Linderborg, Klas; Salaspuro, Mikko; Väkeväinen, Satu

    2011-09-01

    The aim of this study was to explore oral exposure to carcinogenic (group 1) acetaldehyde after single sips of strong alcoholic beverages containing no or high concentrations of acetaldehyde. Eight volunteers tasted 5 ml of ethanol diluted to 40 vol.% with no acetaldehyde and 40 vol.% calvados containing 2400 μM acetaldehyde. Salivary acetaldehyde and ethanol concentrations were measured by gas chromatography. The protocol was repeated after ingestion of ethanol (0.5 g/kg body weight). Salivary acetaldehyde concentration was significantly higher after sipping calvados than after sipping ethanol at 30s both with (215 vs. 128 μmol/l, p<0.05) and without (258 vs. 89 μmol/l, p<0.05) alcohol ingestion. From 2 min onwards there were no significant differences in the decreasing salivary acetaldehyde concentration, which remained above the level of carcinogenicity still at 10 min. The systemic alcohol distribution from blood to saliva had no additional effect on salivary acetaldehyde after sipping of the alcoholic beverages. Carcinogenic concentrations of acetaldehyde are produced from ethanol in the oral cavity instantly after a small sip of strong alcoholic beverage, and the exposure continues for at least 10 min. Acetaldehyde present in the beverage has a short-term effect on total acetaldehyde exposure. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Ab initio calculations of torsionally mediated hyperfine splittings in E states of acetaldehyde

    NASA Astrophysics Data System (ADS)

    Xu, Li-Hong; Reid, E. M.; Guislain, B.; Hougen, J. T.; Alekseev, E. A.; Krapivin, I.

    2017-12-01

    Quantum chemistry packages can be used to predict with reasonable accuracy spin-rotation hyperfine interaction constants for methanol, which contains one methyl-top internal rotor. In this work we use one of these packages to calculate components of the spin-rotation interaction tensor for acetaldehyde. We then use torsion-rotation wavefunctions obtained from a fit to the acetaldehyde torsion-rotation spectrum to calculate the expected magnitude of hyperfine splittings analogous to those observed at relatively high J values in the E symmetry states of methanol. We find that theory does indeed predict doublet splittings at moderate J values in the acetaldehyde torsion-rotation spectrum, which closely resemble those seen in methanol, but that the factor of three decrease in hyperfine spin-rotation constants compared to methanol puts the largest of the acetaldehyde splittings a factor of two below presently available Lamb-dip resolution.

  13. Polymorphism of ethanol-metabolism genes and alcoholism: correlation of allelic variations with the pharmacokinetic and pharmacodynamic consequences.

    PubMed

    Chen, Yi-Chyan; Peng, Giia-Sheun; Wang, Ming-Fang; Tsao, Tien-Ping; Yin, Shih-Jiun

    2009-03-16

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for metabolism of ethanol. Both ADH and ALDH exhibit genetic polymorphisms among racial populations. Functional variant alleles ADH1B*2 and ALDH2*2 have been consistently replicated to show protection against developing alcohol dependence. Multiple logistic regression analyses suggest that ADH1B*2 and ALDH2*2 may independently influence the risk for alcoholism. It has been well documented that homozygosity of ALDH2*2 almost fully protects against developing alcoholism and that the heterozygosity only affords a partial protection to varying degrees. Correlations of blood ethanol and acetaldehyde concentrations, cardiovascular hemodynamic responses, and subjective perceptions have been investigated in men with different combinatorial ADH1B and ALDH2 genotypes following challenge with ethanol for a period of 130 min. The pharmacokinetic and pharmacodynamic consequences indicate that acetaldehyde, rather than ethanol, is primarily responsible for the observed alcohol sensitivity reactions, suggesting that the full protection by ALDH2*2/*2 can be ascribed to the intense unpleasant physiological and psychological reactions caused by persistently elevated blood acetaldehyde after ingesting a small amount of alcohol and that the partial protection by ALDH2*1/*2 can be attributed to a faster elimination of acetaldehyde and the lower accumulation in circulation. ADH1B polymorphism does not significantly contribute to buildup of the blood acetaldehyde. Physiological tolerance or innate insensitivity to acetaldehyde may be crucial for development of alcohol dependence in alcoholics carrying ALDH2*2.

  14. Adsorption, polymerization and decomposition of acetaldehyde on clean and carbon-covered Rh(111) surfaces

    NASA Astrophysics Data System (ADS)

    Kovács, Imre; Farkas, Arnold Péter; Szitás, Ádám; Kónya, Zoltán; Kiss, János

    2017-10-01

    The adsorption and dissociation of acetaldehyde were investigated on clean and carbon-covered Rh(111) single crystal surfaces by electron energy loss spectroscopy (EELS), temperature programmed desorption (TPD), high-resolution electron energy loss spectroscopy (HREELS) and work function (Δφ) measurements. Acetaldehyde is a starting material for the catalytic production of many important chemicals and investigation of its reactions motivated by environmental purposes too. The adsorption of acetaldehyde on clean Rh(111) surface produced various types of adsorption forms. η1-(O)-CH3CHOa and η2-(O,C)-CH3CHOa are developing and characterized by HREELS. η1-CH3CHOa partly desorbed at Tp = 150 K, another part of these species are incorporated in trimer and linear 2D polimer species. The desorption of trimers (at amu 132) were observed in TPD with a peak maximum at Tp = 225 K. Above this temperature acetaldehyde either desorbed or bonded as a stable surface intermediate (η2-CH3CHOa) on the rhodium surface. The molecules decomposed to adsorbed products, and only hydrogen and carbon monoxide were analyzed in TPD. Surface carbon decreased the uptake of adsorbed acetaldehyde, inhibited the formation of polymers, nevertheless, it induced the Csbnd O bond scission and CO formation with 40-50 K lower temperature after higher acetaldehyde exposure.

  15. Acetaldehyde involvement in ethanol's postabsortive effects during early ontogeny.

    PubMed

    March, Samanta M; Abate, P; Molina, Juan C

    2013-01-01

    Clinical and biomedical studies sustains the notion that early ontogeny is a vulnerable window to the impact of alcohol. Experiences with the drug during these stages increase latter disposition to prefer, use or abuse ethanol. This period of enhanced sensitivity to ethanol is accompanied by a high rate of activity in the central catalase system, which metabolizes ethanol in the brain. Acetaldehyde (ACD), the first oxidation product of ethanol, has been found to share many neurobehavioral effects with the drug. Cumulative evidence supports this notion in models employing adults. Nevertheless very few studies have been conducted to analyze the role of ACD in ethanol postabsorptive effects, in newborns or infant rats. In this work we review recent experimental literature that syndicates ACD as a mediator agent of reinforcing aspects of ethanol, during early ontogenetic stages. We also show a meta-analytical correlational approach that proposes how differences in the activity of brain catalase across ontogeny, could be modulating patterns of ethanol consumption.

  16. ALDH2 genotype has no effect on salivary acetaldehyde without the presence of ethanol in the systemic circulation.

    PubMed

    Helminen, Andreas; Väkeväinen, Satu; Salaspuro, Mikko

    2013-01-01

    Acetaldehyde associated with alcoholic beverages was recently classified as carcinogenic (Group 1) to humans based on uniform epidemiological and biochemical evidence. ALDH2 (aldehyde dehydrogenase 2) deficient alcohol consumers are exposed to high concentrations of salivary acetaldehyde and have an increased risk of upper digestive tract cancer. However, this interaction is not seen among ALDH2 deficient non-drinkers or rare drinkers, regardless of their smoking status or consumption of edibles containing ethanol or acetaldehyde. Therefore, the aim of this study was to examine the effect of the ALDH2 genotype on the exposure to locally formed acetaldehyde via the saliva without ethanol ingestion. The ALDH2 genotypes of 17 subjects were determined by PCR-RFLP. The subjects rinsed out their mouths with 5 ml of 40 vol% alcohol for 5 seconds. Salivary ethanol and acetaldehyde levels were measured by gas chromatography. Acetaldehyde reached mutagenic levels rapidly and the exposure continued for up to 20 minutes. The mean salivary acetaldehyde concentrations did not differ between ALDH2 genotypes. For ALDH2 deficient subjects, an elevated exposure to endogenously formed acetaldehyde requires the presence of ethanol in the systemic circulation. Our findings provide a logical explanation for how there is an increased incidence of upper digestive tract cancers among ALDH2 deficient alcohol drinkers, but not among those ALDH2 deficient subjects who are locally exposed to acetaldehyde without bloodborne ethanol being delivered to the saliva. Thus, ALDH2 deficient alcohol drinkers provide a human model for increased local exposure to acetaldehyde derived from the salivary glands.

  17. Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jung, Tae Woo; Lee, Ji Young; Shim, Wan Sub

    2006-02-03

    Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species level and apoptosis. Rosiglitazone, a peroxisome proliferator-activated receptor-{gamma} agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In this study, we investigated the protective effects of rosiglitazone on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by rosiglitazone treatment. Our results suggest that the protective effects of rosiglitazone on acetaldehyde-induced apoptosis may be ascribed to abilitymore » to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that rosiglitazone may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease.« less

  18. Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: A molecular mechanism of protection against alcoholic liver disease.

    PubMed

    Hao, Liuyi; Sun, Qian; Zhong, Wei; Zhang, Wenliang; Sun, Xinguo; Zhou, Zhanxiang

    2018-04-01

    Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD + and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD. Male C57BL/6J mice were exposed to alcohol for 8 weeks with MitoQ supplementation (5mg/kg/d) for the last 4 weeks. MitoQ ameliorated alcohol-induced oxidative/nitrosative stress and glutathione deficiency. It also reversed alcohol-reduced hepatic ALDH activity and accelerated acetaldehyde clearance through modulating ALDH2 cysteine S-nitrosylation, tyrosine nitration and 4-hydroxynonenol adducts formation. MitoQ ameliorated nitric oxide (NO) donor-mediated ADLH2 S-nitrosylation and nitration in Hepa-1c1c7 cells under glutathion depletion condition. In addition, alcohol-increased circulating acetaldehyde levels were accompanied by reduced intestinal ALDH activity and impaired intestinal barrier. In accordance, MitoQ reversed alcohol-increased plasma endotoxin levels and hepatic toll-like receptor 4 (TLR4)-NF-κB signaling along with subsequent inhibition of inflammatory cell infiltration. MitoQ also reversed alcohol-induced hepatic lipid accumulation through enhancing fatty acid β-oxidation. Alcohol-induced ER stress and apoptotic cell death signaling were reversed by MitoQ. This study demonstrated that speeding up acetaldehyde clearance by preserving ALDH2 activity critically mediates the beneficial effect of MitoQ on alcohol-induced pathogenesis at the gut-liver axis. Copyright © 2017 The Authors. Published by Elsevier B

  19. Abundances of ethylene oxide and acetaldehyde in hot molecular cloud cores

    NASA Technical Reports Server (NTRS)

    Nummelin, A.; Dickens, J. E.; Bergman, P.; Hjalmarson, A.; Irvine, W. M.; Ikeda, M.; Ohishi, M.

    1998-01-01

    We have searched for millimetre-wave line emission from ethylene oxide (c-C2H4O) and its structural isomer acetaldehyde (CH3CHO) in 11 molecular clouds using SEST. Ethylene oxide and acetaldehyde were detected through multiple lines in the hot cores NGC 6334F, G327.3-0.6, G31.41+0.31, and G34.3+0.2. Acetaldehyde was also detected towards G10.47+0.03, G322.2+0.6, and Orion 3'N, and one ethylene oxide line was tentatively detected in G10.47+0.03. Column densities and rotational excitation temperatures were derived using a procedure which fits the observed line intensifies by finding the minimum chi 2-value. The resulting rotational excitation temperatures of ethylene oxide and acetaldehyde are in the range 16-38 K, indicating that these species are excited in the outer, cooler parts of the hot cores or that the excitation is significantly subthermal. For an assumed source size of 20", the deduced column densities are (0.6-1)x10(14) cm-2 for ethylene oxide and (2-5)x10(14) cm-2 for acetaldehyde. The fractional abundances with respect to H2 are X[c-C2H4O]=(2-6)xl0(-10), and X[CH3CHO]=(0.8-3)x10(-9). The ratio X[CH3CHO]/X[c-C2H4O] varies between 2.6 (NGC 6334F) and 8.5 (G327.3-0.6). We also detected and analysed multiple transitions of CH3OH, CH3OCH3, C2H5OH, and HCOOH. The chemical, and possibly evolutionary, states of NGC 6334F, G327.3-0.6, G31.41+0.31, and G34.3+0.2 seem to be very similar.

  20. Structure and spectroscopic propierties of imine acetaldehyde: a possible interstellar molecule

    NASA Astrophysics Data System (ADS)

    Redondo, Pilar; Largo, Antonio; Barrientos, Carmen

    2018-05-01

    A previous theoretical study shows that imine acetaldehyde can be obtained from the reaction between protonated vinyl alcohol and azanone. Therefore, imine acetaldehyde could be considered as a good molecule candidate to be found in space and could evolve to more complex organic molecules of prebiotic interest. In the present work, we carried out a computational study of the different conformers of imine acetaldehyde. For characterize its conformers we apply a composite approach which considers the extrapolation to the complete basis set (CBS) limit and core-valence (CV) electron correlation corrections at the at the CC level including single and double excitations and a perturbative treatment of triple excitations (CCSD(T)). This approach provides bond distances with an accuracy of 0.001-0.002 Åand angles accurate to 0.05-0.1°. Vibrational harmonic and anharmonic frequencies and IR intensities are also reported at the CCSD level. The most stable structure corresponds to an antiperiplanar disposition of the oxygen atom and of NH group with the hydrogen atom of the NH group addressed outside the skeleton. Interconversion processes between the four conformers characterized are studied. The lowest isomerization barrier is estimated to be around 1.2 kcal mol-1, making these processes unlikely under low temperature conditions, such as those reigning in the interstellar medium. The reported, at "spectroscopic" accuracy, stabilities, molecular structures, as well as spectroscopic parameters for the four imine acetaldehyde conformers that could help in their laboratory or astronomical detection.

  1. Acetaldehyde as an intermediate in the electroreduction of carbon monoxide to ethanol on oxide-derived copper

    DOE PAGES

    Bertheussen, Erlend; Verdaguer-Casadevall, Arnau; Ravasio, Davide; ...

    2015-12-21

    Oxide-derived copper (OD-Cu) electrodes exhibit unprecedented CO reduction performance towards liquid fuels, producing ethanol and acetate with >50 % Faradaic efficiency at -0.3 V (vs. RHE). By using static headspace-gas chromatography for liquid phase analysis, we identify acetaldehyde as a minor product and key intermediate in the electroreduction of CO to ethanol on OD-Cu electrodes. Acetaldehyde is produced with a Faradaic efficiency of ≈5 % at -0.33 V (vs. RHE). We show that acetaldehyde forms at low steady-state concentrations, and that free acetaldehyde is difficult to detect in alkaline solutions using NMR spectroscopy, requiring alternative methods for detection and quantification.more » Our results indicate an important step towards understanding the CO reduction mechanism on OD-Cu electrodes.« less

  2. Low acetaldehyde collection efficiencies for 24-hour sampling with 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents.

    PubMed

    Herrington, Jason S; Fan, Zhi-Hua Tina; Lioy, Paul J; Zhang, Junfeng Jim

    2007-01-15

    Airborne aldehyde and ketone (carbonyl) sampling methodologies based on derivatization with 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents could unequivocally be considered the "gold" standard. Originally developed in the late 1970s, these methods have been extensively evaluated and developed up to the present day. However, these methods have been inadequately evaluated for the long-term (i.e., 24 h or greater) sampling collection efficiency (CE) of carbonyls other than formaldehyde. The current body of literature fails to demonstrate that DNPH-coated solid sorbent sampling methods have acceptable CEs for the long-term sampling of carbonyls other than formaldehyde. Despite this, such methods are widely used to report the concentrations of multiple carbonyls from long-term sampling, assuming approximately 100% CEs. Laboratory experiments were conducted in this study to evaluate the long-term formaldehyde and acetaldehyde sampling CEs for several commonly used DNPH-coated solid sorbents. Results from sampling known concentrations of formaldehyde and acetaldehyde generated in a dynamic atmosphere generation system demonstrate that the 24-hour formaldehyde sampling CEs ranged from 83 to 133%, confirming the findings made in previous studies. However, the 24-hour acetaldehyde sampling CEs ranged from 1 to 62%. Attempts to increase the acetaldehyde CEs by adding acid to the samples post sampling were unsuccessful. These results indicate that assuming approximately 100% CEs for 24-hour acetaldehyde sampling, as commonly done with DNPH-coated solid sorbent methods, would substantially under estimate acetaldehyde concentrations.

  3. Formaldehyde and acetaldehyde emissions from residential wood combustion in Portugal

    NASA Astrophysics Data System (ADS)

    Cerqueira, Mário; Gomes, Luís; Tarelho, Luís; Pio, Casimiro

    2013-06-01

    A series of experiments were conducted to characterize formaldehyde and acetaldehyde emissions from residential combustion of common wood species growing in Portugal. Five types of wood were investigated: maritime pine (Pinus pinaster), eucalyptus (Eucalyptus globulus), cork oak (Quercus suber), holm oak (Quercus rotundifolia) and pyrenean oak (Quercus pyrenaica). Laboratory experiments were performed with a typical wood stove used for domestic heating in Portugal and operating under realistic home conditions. Aldehydes were sampled from diluted combustion flue gas using silica cartridges coated with 2,4-dinitrophenylhydrazine and analyzed by high performance liquid chromatography with diode array detection. The average formaldehyde to acetaldehyde concentration ratio (molar basis) in the stove flue gas was in the range of 2.1-2.9. Among the tested wood types, pyrenean oak produced the highest emissions for both formaldehyde and acetaldehyde: 1772 ± 649 and 1110 ± 454 mg kg-1 biomass burned (dry basis), respectively. By contrast, maritime pine produced the lowest emissions: 653 ± 151 and 371 ± 162 mg kg-1 biomass (dry basis) burned, respectively. Aldehydes were sampled separately during distinct periods of the holm oak wood combustion cycles. Significant variations in the flue gas concentrations were found, with higher values measured during the devolatilization stage than in the flaming and smoldering stages.

  4. On the Reaction Mechanism of Acetaldehyde Decomposition on Mo(110)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mei, Donghai; Karim, Ayman M.; Wang, Yong

    2012-02-16

    The strong Mo-O bond strength provides promising reactivity of Mo-based catalysts for the deoxygenation of biomass-derived oxygenates. Combining the novel dimer saddle point searching method with periodic spin-polarized density functional theory calculations, we investigated the reaction pathways of a acetaldehyde decomposition on the clean Mo(110) surface. Two reaction pathways were identified, a selective deoxygenation and a nonselective fragmentation pathways. We found that acetaldehyde preferentially adsorbs at the pseudo 3-fold hollow site in the η2(C,O) configuration on Mo(110). Among four possible bond (β-C-H, γ-C-H, C-O and C-C) cleavages, the initial decomposition of the adsorbed acetaldehyde produces either ethylidene via the C-Omore » bond scission or acetyl via the β-C-H bond scission while the C-C and the γ-C-H bond cleavages of acetaldehyde leading to the formation of methyl (and formyl) and formylmethyl are unlikely. Further dehydrogenations of ethylidene into either ethylidyne or vinyl are competing and very facile with low activation barriers of 0.24 and 0.31 eV, respectively. Concurrently, the formed acetyl would deoxygenate into ethylidyne via the C-O cleavage rather than breaking the C-C or the C-H bonds. The selective deoxygenation of acetaldehyde forming ethylene is inhibited by relatively weaker hydrogenation capability of the Mo(110) surface. Instead, the nonselective pathway via vinyl and vinylidene dehydrogenations to ethynyl as the final hydrocarbon fragment is kinetically favorable. On the other hand, the strong interaction between ethylene and the Mo(110) surface also leads to ethylene decomposition instead of desorption into the gas phase. This work was financially supported by the National Advanced Biofuels Consortium (NABC). Computing time was granted by a user project (emsl42292) at the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). This work was financially

  5. Adsorption and Reaction of Acetaldehyde on Shape-Controlled CeO2 Nanocrystals: Elucidation of Structure-function Relationships

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mann, Amanda K; Wu, Zili; Calaza, Florencia

    2014-01-01

    CeO2 cubes with {100} facets, octahedra with {111} facets, and wires with highly defective structures were utilized to probe the structure-dependent reactivity of acetaldehyde. Using temperature-programmed desorption (TPD), temperature-programmed surface reactions (TPSR), and in situ infrared spectroscopy it was found that acetaldehyde desorbs unreacted or undergoes reduction, coupling, or C-C bond scission reactions depending on the surface structure of CeO2. Room temperature FTIR indicates that acetaldehyde binds primarily as 1-acetaldehyde on the octahedra, in a variety of conformations on the cubes, including coupling products and acetate and enolate species, and primarily as coupling products on the wires. The percent consumptionmore » of acetaldehyde follows the order of wires > cubes > octahedra. All the nanoshapes produce the coupling product crotonaldehyde; however, the selectivity to produce ethanol follows the order wires cubes >> octahedra. The selectivity and other differences can be attributed to the variation in the basicity of the surfaces, defects densities, coordination numbers of surface atoms, and the reducibility of the nanoshapes.« less

  6. Increased levels of the acetaldehyde-derived DNA adduct N 2-ethyldeoxyguanosine in oral mucosa DNA from Rhesus monkeys exposed to alcohol

    PubMed Central

    Balbo, Silvia; Juanes, Rita Cervera; Khariwala, Samir; Baker, Erich J.; Daunais, James B.; Grant, Kathleen A.

    2016-01-01

    Alcohol is a human carcinogen. A causal link has been established between alcohol drinking and cancers of the upper aerodigestive tract, colon, liver and breast. Despite this established association, the underlying mechanisms of alcohol-induced carcinogenesis remain unclear. Various mechanisms may come into play depending on the type of cancer; however, convincing evidence supports the concept that ethanol’s major metabolite acetaldehyde may play a major role. Acetaldehyde can react with DNA forming adducts which can serve as biomarkers of carcinogen exposure and potentially of cancer risk. The major DNA adduct formed from this reaction is N 2-ethylidenedeoxyguanosine, which can be quantified as its reduced form N 2-ethyl-dG by LC-ESI-MS/MS. To investigate the potential use of N 2-ethyl-dG as a biomarker of alcohol-induced DNA damage, we quantified this adduct in DNA from the oral, oesophageal and mammary gland tissues from rhesus monkeys exposed to alcohol drinking over their lifetimes and compared it to controls. N 2-Ethyl-dG levels were significantly higher in the oral mucosa DNA of the exposed animals. Levels of the DNA adduct measured in the oesophageal mucosa of exposed animals were not significantly different from controls. A correlation between the levels measured in the oral and oesophageal DNA, however, was observed, suggesting a common source of formation of the DNA adducts. N 2-Ethyl-dG was measured in mammary gland DNA from a small cohort of female animals, but no difference was observed between exposed animals and controls. These results support the hypothesis that acetaldehyde induces DNA damage in the oral mucosa of alcohol-exposed animals and that it may play role in the alcohol-induced carcinogenic process. The decrease of N 2-ethyl-dG levels in exposed tissues further removed from the mouth also suggests a role of alcohol metabolism in the oral cavity, which may be considered separately from ethanol liver metabolism in the investigation of

  7. Artisanal alcohol production in Mayan Guatemala: chemical safety evaluation with special regard to acetaldehyde contamination.

    PubMed

    Kanteres, Fotis; Rehm, Jürgen; Lachenmeier, Dirk W

    2009-11-01

    There is a lack of knowledge regarding the composition, production, distribution, and consumption of artisanal alcohol, particularly in the developing world. In Nahualá, an indigenous Mayan municipality located in highland Guatemala, heavy alcohol consumption appears to have had a significant negative impact on health, a major role in cases of violence and domestic abuse, and a link to street habitation. Cuxa, an artisanally, as well as commercially produced sugarcane alcohol, is widely consumed by heavy drinkers in this community. Cuxa samples from all distribution points in the community were obtained and chemically analyzed for health-relevant constituents and contaminants including methanol, acetaldehyde, higher alcohols, and metals. From those, only acetaldehyde was confirmed to be present in unusually high levels (up to 126 g/hl of pure alcohol), particularly in samples that were produced clandestinely. Acetaldehyde has been evaluated as "possibly carcinogenic" and has also been identified as having significant human exposure in a recent risk assessment. This study explores the reasons for the elevated levels of acetaldehyde, through both sampling and analyses of raw and intermediary products of cuxa production, as well as interviews from producers of the clandestine alcohol. For further insight, we experimentally produced this alcohol in our laboratory, based on the directions provided by the producers, as well as materials from the town itself. Based on these data, the origin of the acetaldehyde contamination appears to be due to chemical changes induced during processing, with the major causative factors consisting of poor hygiene, aerobic working conditions, and inadequate yeast strains, compounded by flawed distillation methodology that neglects separation of the first fractions of the distillate. These results indicate a preventable public health concern for consumers, which can be overcome through education about good manufacturing practices, as well

  8. Formation and Accumulation of Acetaldehyde and Strecker Aldehydes during Red Wine Oxidation.

    PubMed

    Bueno, Mónica; Marrufo-Curtido, Almudena; Carrascón, Vanesa; Fernández-Zurbano, Purificación; Escudero, Ana; Ferreira, Vicente

    2018-01-01

    The main aim of the present work is to study the accumulation of acetaldehyde and Strecker aldehydes (isobutyraldehyde, 2-methylbutanal, isovaleraldehyde, methional, phenylacetaldehyde) during the oxidation of red wines, and to relate the patterns of accumulation to the wine chemical composition. For that, eight different wines, extensively chemically characterized, were subjected at 25°C to three different controlled O 2 exposure conditions: low (10 mg L -1 ) and medium or high (the stoichiometrically required amount to oxidize all wine total SO 2 plus 18 or 32 mg L -1 , respectively). Levels of volatile aldehydes and carbonyls were then determined and processed by different statistical techniques. Results showed that young wines (<2 years-old bottled wines) hardly accumulate any acetaldehyde regardless of the O 2 consumed. In contrast, aged wines (>3 years-old bottled wines) accumulated acetaldehyde while their content in SO 2 was not null, and the aged wine containing lowest polyphenols accumulated it throughout the whole process. Models suggest that the ability of a wine to accumulate acetaldehyde is positively related to its content in combined SO 2 , in epigallocatechin and to the mean degree of polymerization, and negatively to its content in Aldehyde Reactive Polyphenols (ARPs) which, attending to our models, are anthocyanins and small tannins. The accumulation of Strecker aldehydes is directly proportional to the wine content in the amino acid precursor, being the proportionality factor much higher for aged wines, except for phenylacetaldehyde, for which the opposite pattern was observed. Models suggest that non-aromatic Strecker aldehydes share with acetaldehyde a strong affinity toward ARPs and that the specific pattern of phenylacetaldehyde is likely due to a much reduced reactivity toward ARPs, to the possibility that diacetyl induces Strecker degradation of phenyl alanine and to the potential higher reactivity of this amino acid to some quinones

  9. Formation and Accumulation of Acetaldehyde and Strecker Aldehydes during Red Wine Oxidation

    PubMed Central

    Bueno, Mónica; Marrufo-Curtido, Almudena; Carrascón, Vanesa; Fernández-Zurbano, Purificación; Escudero, Ana; Ferreira, Vicente

    2018-01-01

    The main aim of the present work is to study the accumulation of acetaldehyde and Strecker aldehydes (isobutyraldehyde, 2-methylbutanal, isovaleraldehyde, methional, phenylacetaldehyde) during the oxidation of red wines, and to relate the patterns of accumulation to the wine chemical composition. For that, eight different wines, extensively chemically characterized, were subjected at 25°C to three different controlled O2 exposure conditions: low (10 mg L−1) and medium or high (the stoichiometrically required amount to oxidize all wine total SO2 plus 18 or 32 mg L−1, respectively). Levels of volatile aldehydes and carbonyls were then determined and processed by different statistical techniques. Results showed that young wines (<2 years-old bottled wines) hardly accumulate any acetaldehyde regardless of the O2 consumed. In contrast, aged wines (>3 years-old bottled wines) accumulated acetaldehyde while their content in SO2 was not null, and the aged wine containing lowest polyphenols accumulated it throughout the whole process. Models suggest that the ability of a wine to accumulate acetaldehyde is positively related to its content in combined SO2, in epigallocatechin and to the mean degree of polymerization, and negatively to its content in Aldehyde Reactive Polyphenols (ARPs) which, attending to our models, are anthocyanins and small tannins. The accumulation of Strecker aldehydes is directly proportional to the wine content in the amino acid precursor, being the proportionality factor much higher for aged wines, except for phenylacetaldehyde, for which the opposite pattern was observed. Models suggest that non-aromatic Strecker aldehydes share with acetaldehyde a strong affinity toward ARPs and that the specific pattern of phenylacetaldehyde is likely due to a much reduced reactivity toward ARPs, to the possibility that diacetyl induces Strecker degradation of phenyl alanine and to the potential higher reactivity of this amino acid to some quinones derived

  10. Formation and accumulation of acetaldehyde and Strecker aldehydes during red wine oxidation

    NASA Astrophysics Data System (ADS)

    Bueno, Mónica; Marrufo-Curtido, Almudena; Carrascón, Vanesa; Fernández-Zurbano, Purificación; Escudero, Ana; Ferreira, Vicente

    2018-02-01

    The main aim of the present work is to study the accumulation of acetaldehyde and Strecker aldehydes (isobutyraldehyde, 2-methylbutanal, isovaleraldehyde, methional, phenylacetaldehyde) during the oxidation of red wines, and to relate the patterns of accumulation to the wine chemical composition. For that, eight different wines, extensively chemically characterized, were subjected at 25°C to three different controlled O2 exposure conditions: low (10 mg L-1) and medium or high (the stoichiometrically required amount to oxidize all wine total SO2 plus 18 or 32 mg L-1, respectively). Levels of volatile aldehydes and carbonyls were then determined and processed by different statistical techniques. Results showed that young wines (<2 years-old bottled wines) hardly accumulate any acetaldehyde regardless of the O2 consumed. In contrast, aged wines (>3 years-old bottled wines) accumulated acetaldehyde while their content in SO2 was not null, and the aged wine containing lowest polyphenols accumulated it throughout the whole process. Models suggest that the ability of a wine to accumulate acetaldehyde is positively related to its content in combined SO2, in epigallocatechin and to the mean degree of polymerization, and negatively to its content in Aldehyde Reactive Polyphenols (ARPs) which, attending to our models, are anthocyanins and small tannins. The accumulation of Strecker aldehydes is directly proportional to the wine content in the amino acid precursor, being the proportionality factor much higher for aged wines, except for phenylacetaldehyde, for which the opposite pattern was observed. Models suggest that non-aromatic Strecker aldehydes share with acetaldehyde a strong affinity towards ARPs and that the specific pattern of phenylacetaldehyde is likely due to a much reduced reactivity towards ARPs, to the possibility that diacetyl induces Strecker degradation of phenyl alanine and to the potential higher reactivity of this amino acid to some quinones derived from

  11. BIOGENIC SOURCES FOR FORMALDEHYDE AND ACETALDEHYDE DURING SUMMER MONTHS

    EPA Science Inventory

    Photochemical modeling estimated contributions to ambient concentrations of formaldehyde and acetaldehyde from biogenic emissions over the continental United States during January 2001 (Eos Trans. AGU, 83(47), Fall Meet. Suppl., Abstract A52B-0117). Results showed that maximum co...

  12. An improved biosensor for acetaldehyde determination using a bienzymatic strategy at poly(neutral red) modified carbon film electrodes.

    PubMed

    Ghica, Mariana Emilia; Pauliukaite, Rasa; Marchand, Nicolas; Devic, Eric; Brett, Christopher M A

    2007-05-15

    Improved biosensors for acetaldehyde determination have been developed using a bienzymatic strategy, based on a mediator-modified carbon film electrode and co-immobilisation of NADH oxidase and aldehyde dehydrogenase. Modification of the carbon film electrode with poly(neutral red) mediator resulted in a sensitive, low-cost and reliable NADH detector. Immobilisation of the enzymes was performed using encapsulation in a sol-gel matrix or cross-linking with glutaraldehyde. The bienzymatic biosensors were characterized by studying the influence of pH, applied potential and co-factors. The sol-gel and glutaraldehyde biosensors showed a linear response up to 60 microM and 100 microM, respectively, with detection limits of 2.6 microM and 3.3 microM and sensitivities were 1.7 microA mM(-1) and 5.6 microA mM(-1). The optimised biosensors showed good stability and good selectivity and have been tested for application for the determination of acetaldehyde in natural samples such as wine.

  13. Millimeter and submillimeter wave spectra of mono-13C-acetaldehydes

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Ilyushin, V. V.; Guillemin, J. C.

    2015-07-01

    Context. The acetaldehyde molecule is ubiquitous in the interstellar medium of our galaxy, and due to its dense and complex spectrum, large dipole moment, and several low-lying torsional states, acetaldehyde is considered to be a "weed" molecule for radio astronomy observations. Mono-13C acetaldehydes 13CH3CHO and CH313CHO are likely to be identified in astronomical surveys, such as those available with the very sensitive ALMA telescope. Laboratory measurements and analysis of the millimeter and submillimeter-wave spectra are the prerequisites for the successful radioastronomical search for the new interstellar molecular species, as well as for new isotopologs of already detected interstellar molecules. Aims: In this context, to provide reliable predictions of 13CH3CHO and CH313CHO spectra in millimeter and submillimeter wave ranges, we study rotational spectra of these species in the frequency range from 50 to 945 GHz. Methods: The spectra of mono-13C acetaldehydes were recorded using the spectrometer based on Schottky-diode frequencymultiplication chains in the Lille laboratory. The rotational spectra of 13CH3CHO and CH313CHO molecules were analyzed using the Rho axis method. Results: In the recorded spectra we have assigned 6884 for the 13CH3CHO species and 6458 for CH313CHO species new rotational transitions belonging to the ground, first, and second excited torsional states. These measurements were fitted together with previously published data to the Hamiltonian models that use 91 and 87 parameters to achieve overall weighted rms deviations 0.88 for the 13CH3CHO species and 0.95 for CH313CHO. On the basis of the new spectroscopic results, predictions of transition frequencies in the frequency range up to 1 THz with J ≤ 60 and Ka ≤ 20 are presented for both isotopologs. Full Tables 3-6 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/579/A46

  14. Redirection of the Reaction Specificity of a Thermophilic Acetolactate Synthase toward Acetaldehyde Formation

    PubMed Central

    Cheng, Maria; Yoshiyasu, Hayato; Okano, Kenji; Ohtake, Hisao; Honda, Kohsuke

    2016-01-01

    Acetolactate synthase and pyruvate decarboxylase are thiamine pyrophosphate-dependent enzymes that convert pyruvate into acetolactate and acetaldehyde, respectively. Although the former are encoded in the genomes of many thermophiles and hyperthermophiles, the latter has been found only in mesophilic organisms. In this study, the reaction specificity of acetolactate synthase from Thermus thermophilus was redirected to catalyze acetaldehyde formation to develop a thermophilic pyruvate decarboxylase. Error-prone PCR and mutant library screening led to the identification of a quadruple mutant with 3.1-fold higher acetaldehyde-forming activity than the wild-type. Site-directed mutagenesis experiments revealed that the increased activity of the mutant was due to H474R amino acid substitution, which likely generated two new hydrogen bonds near the thiamine pyrophosphate-binding site. These hydrogen bonds might result in the better accessibility of H+ to the substrate-cofactor-enzyme intermediate and a shift in the reaction specificity of the enzyme. PMID:26731734

  15. Astaxanthin Inhibits Acetaldehyde-Induced Cytotoxicity in SH-SY5Y Cells by Modulating Akt/CREB and p38MAPK/ERK Signaling Pathways.

    PubMed

    Yan, Tingting; Zhao, Yan; Zhang, Xia; Lin, Xiaotong

    2016-03-10

    Excessive alcohol consumption can lead to brain tissue damage and cognitive dysfunction. Acetaldehyde, the most toxic metabolite of ethanol, mediates the brain tissue damage and cognitive dysfunction induced by chronic excessive alcohol consumption. In this study, the effect of astaxanthin, a marine bioactive compound, on acetaldehyde-induced cytotoxicity was investigated in SH-SY5Y cells. It was found that astaxanthin protected cells from apoptosis by ameliorating the effect of acetaldehyde on the expression of Bcl-2 family proteins, preventing the reduction of anti-apoptotic protein Bcl-2 and the increase of pro-apoptotic protein Bak induced by acetaldehyde. Further analyses showed that astaxanthin treatment inhibited acetaldehyde-induced reduction of the levels of activated Akt and cyclic AMP-responsive element binding protein (CREB). Astaxanthin treatment also prevented acetaldehyde-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK) and decrease of the level of activated extracellular signal-regulated kinases (ERKs). Activation of Akt/CREB pathway promotes cell survival and is involved in the upregulation of Bcl-2 gene. P38MAPK plays a critical role in apoptotic events while ERKs mediates the inhibition of apoptosis. Thus, astaxanthin may inhibit acetaldehyde-induced apoptosis through promoting the activation of Akt/CREB and ERKs and blocking the activation of p38MAPK. In addition, astaxanthin treatment suppressed the oxidative stress induced by acetaldehyde and restored the antioxidative capacity of SH-SY5Y cells. Therefore, astaxanthin may protect cells against acetaldehyde-induced cytotoxicity through maintaining redox balance and modulating apoptotic and survival signals. The results suggest that astaxanthin treatment may be beneficial for preventing neurotoxicity associated with acetaldehyde and excessive alcohol consumption.

  16. Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

    PubMed Central

    2012-01-01

    Background Viability in a non dividing state is referred to as chronological life span (CLS). Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content. PMID:22873488

  17. Facilitated ethanol metabolism promotes cardiomyocyte contractile dysfunction through autophagy in murine hearts.

    PubMed

    Guo, Rui; Hu, Nan; Kandadi, Machender R; Ren, Jun

    2012-04-01

    Chronic drinking leads to myocardial contractile dysfunction where ethanol metabolism plays an essential role. Acetaldehyde, the main ethanol metabolite, mediates alcohol-induced cell injury although the underlying mechanism is still elusive. This study was designed to examine the mechanism involved in accelerated ethanol metabolism-induced cardiac defect with a focus on autophagy. Wild-type FVB and cardiac-specific overexpression of alcohol dehydrogenase mice were placed on a 4% nutrition-balanced alcohol diet for 8 weeks. Myocardial histology, immunohistochemistry, autophagy markers and signal molecules were examined. Expression of micro RNA miR-30a, a potential target of Beclin 1, was evaluated by real-time PCR. Chronic alcohol intake led to cardiac acetaldehyde accumulation, hypertrophy and overt autophagosome accumulation (LC3-II and Atg7), the effect of which was accentuated by ADH. Signaling molecules governing autophagy initiation including class III PtdIns3K, phosphorylation of mTOR and p70S6K were enhanced and dampened, respectively, following alcohol intake. These alcohol-induced signaling responses were augmented by ADH. ADH accentuated or unmasked alcohol-induced downregulation of Bcl-2, Bcl-xL and MiR-30a. Interestingly, ADH aggravated alcohol-induced p62 accumulation. Autophagy inhibition using 3-MA abolished alcohol-induced cardiomyocyte contractile anomalies. Moreover, acetaldehyde led to cardiomyocyte contractile dysfunction and autophagy induction, which was ablated by 3-MA. Ethanol or acetaldehyde increased GFP-LC3 puncta in H9c2 cells, the effect of which was ablated by 3-MA but unaffected by lysosomal inhibition using bafilomycin A(1), E64D and pepstatin A. In summary, these data suggested that facilitated acetaldehyde production via ADH following alcohol intake triggered cardiac autophagosome formation along with impaired lysosomal degradation, en route to myocardial defect.

  18. [Determination of formaldehyde and acetaldehyde in packaging paper by dansylhydrazine derivatization-high performance liquid chromatography-fluorescence detection].

    PubMed

    Gong, Shuguo; Liang, Yong; Tang, Liyun; Huang, Ping; Dai, Yunhui

    2017-07-08

    A high performance liquid chromatography with fluorescence detection (HPLC-FLD) method was developed for the simultaneous determination of formaldehyde and acetaldehyde in packaging paper by dansylhydrazine (DNSH) derivatization. The samples were extracted by derivatization reagent for 30 min, and derived for 24 h. After purifying treatment with a PSA/C18 cartridge, a Diamonsil ® C18 column (150 mm×4.6 mm, 5 μ m) was used as stationary phase for separation, the mixtures of acetic acid aqueous solution (pH 2.55)-acetonitrile were used as mobile phases by gradient elution, and the excitation and emission wavelengths were 330 nm and 484 nm, respectively. The results showed that the recoveries of formaldehyde and acetaldehyde spiked in the samples were 81.64%-106.78%, and the relative standard deviations (RSDs) were 2.02%-5.53% ( n =5). The limits of detection of formaldehyde and acetaldehyde were 19.2 μ g/kg and 20.7 μ g/kg, respectively. The limits of quantification of formaldehyde and acetaldehyde were 63.9 μ g/kg and 69.1 μ g/kg, respectively. The method is simple, sensitive and reproducible. It provides a basic approach for the determination of trace formaldehyde and acetaldehyde.

  19. Experimental and modeling study of the oxidation of acetaldehyde in an atmospheric-pressure pulsed corona discharge

    NASA Astrophysics Data System (ADS)

    Klett, C.; Touchard, S.; Vega-Gonzalez, A.; Redolfi, M.; Bonnin, X.; Hassouni, K.; Duten, X.

    2012-08-01

    This paper reports the results obtained for the degradation of acetaldehyde by an atmospheric plasma corona discharge working in a pulsed regime. It was shown that a few hundred ppm of acetaldehyde diluted in a pure N2 gas flow can be removed up to 80% by a discharge fed with an electric power lower than 1 W. Under the same conditions, adding up to 5% of O2 allowed the removal of up to 95% of the initial acetaldehyde. The main identified end products were CO2, CO and methanol. A quasi-homogeneous zero-dimensional chemical model was developed to investigate the respective efficiency of the discharge and post-discharge periods in the global removal of the pollutant. The identified main pathways of acetaldehyde degradation were quenching of N2 metastable states during plasma pulses and oxidation by O and OH radicals during the post-discharge. This latter contribution increased with input power because of ozone accumulation in the gas mixture acting as an additional oxygen reservoir.

  20. Synthesis of nanoporous carbohydrate metal-organic framework and encapsulation of acetaldehyde

    NASA Astrophysics Data System (ADS)

    Al-Ghamdi, Saleh; Kathuria, Ajay; Abiad, Mohamad; Auras, Rafael

    2016-10-01

    Gamma cyclodextrin (γ-CD) metal organic frameworks (CDMOFs) were synthesized by coordinating γ-CDs with potassium hydroxide (KOH), referred hereafter as CDMOF-a, and potassium benzoate (C7H5KO2), denoted as CDMOF-b. The obtained CDMOF structures were characterized using nitrogen sorption isotherm, thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). High surface areas were achieved by the γ-CD based MOF structures where the Langmuir specific surface areas (SSA) of CDMOF-a and CDMOF-b were determined as 1376 m2 g-1 and 607 m2 g-1; respectively. The dehydrated CDMOF structures demonstrated good thermal stability up to 250 °C as observed by the TGA studies. XRD results for CDMOF-a and CDMOF-b reveal a body centered-cubic (BCC) and trigonal crystal system; respectively. Due to its accessible porous structure and high surface area, acetaldehyde was successfully encapsulated in CDMOF-b. During the release kinetic studies, we observed peak release of 53 μg of acetaldehyde per g of CDMOF-b, which was 100 times greater than previously reported encapsulation in β-CD. However, aldol condensation reaction occurred during encapsulation of acetaldehyde into CDMOF-a. This research work demonstrates the potential to encapsulate volatile organic compounds in CDMOF-b, and their associated release for applications including food, pharmaceuticals and packaging.

  1. Terahertz Spectroscopy of Deuterated Acetaldehyde: CH_2DCHO

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Coudert, L. H.; Guillemin, J.-C.

    2014-06-01

    This study follows our recent investigations about deuterated methyl-top species of complex organic molecules: methanol, methyl formate, In particular these works led the first ISM detection of HCOOCH_2D and CH_2DOCH_3. Acetaldehyde is not very abundant in the ISM, but this is a very interesting case from the spectroscopic point of view as it is an intermediate case between methyl formate and methanol. In the normal species of acetaldehyde, the barrier to internal rotation which is close to the value in methyl formate: 373 cm-1. However, the value of the Coriolis coupling constant ρ is 0.33 in acetaldehyde which is a much larger value than in methyl formate, 0.08, meaning that the coupling between the torsion and the overall rotation is more important. The sample was not a commercial one and half of its amount is the normal species which leads to a more difficult line assignment. The spectra were recorded in Lille between 75 and 950 GHz with a solid-state submillimeter-wave spectrometer. The starting point of the analysis was the centimeter-wave measurements carried out for the sym and asym- conformers. A comparison between the approach developed for deuterated methyl formate (HCOOCH_2D), based on the water dimer formalism, and that designed recently for deuterated methanola (CH_2DOH) will be presented. This work is supported by the CNES and the Action sur Projets de l'INSU, PCMI. Coudert, L. H.; et al. J. Chem. Phys., 140, (2014) 64307 Coudert, L. H.; et al. ApJ, 779, (2013) 119 Richard, C.; et al. A&A, 552, (2013) A117 Smirnov, I. A.; et al. J. Mol. Spectrosc., 295 (2014) 44 Ilyushin, V.; et al. J. Mol. Spectrosc., 255 (2009) 32 Turner, P. H.; and Cox, A. P. Chem. Phys. Lett., 42, (1976) 84 Turner, P. H.; Cox, A. P.; and Hardy, J. A. J.C.S. Farady Trans., 2, (1981) 1217

  2. Caffeine Inhibits the Activation of Hepatic Stellate Cells Induced by Acetaldehyde via Adenosine A2A Receptor Mediated by the cAMP/PKA/SRC/ERK1/2/P38 MAPK Signal Pathway

    PubMed Central

    Yang, Wanzhi; Wang, Qi; Zhao, Han; Yang, Feng; Lv, Xiongwen; Li, Jun

    2014-01-01

    Hepatic stellate cell (HSC) activation is an essential event during alcoholic liver fibrosis. Evidence suggests that adenosine aggravates liver fibrosis via the adenosine A2A receptor (A2AR). Caffeine, which is being widely consumed during daily life, inhibits the action of adenosine. In this study, we attempted to validate the hypothesis that caffeine influences acetaldehyde-induced HSC activation by acting on A2AR. Acetaldehyde at 50, 100, 200, and 400 μM significantly increased HSC-T6 cells proliferation, and cell proliferation reached a maximum at 48 h after exposure to 200 μM acetaldehyde. Caffeine and the A2AR antagonist ZM241385 decreased the cell viability and inhibited the expression of procollagen type I and type III in acetaldehyde-induced HSC-T6 cells. In addition, the inhibitory effect of caffeine on the expression of procollagen type I was regulated by A2AR-mediated signal pathway involving cAMP, PKA, SRC, and ERK1/2. Interestingly, caffeine’s inhibitory effect on the expression of procollagen type III may depend upon the A2AR-mediated P38 MAPK-dependent pathway. Conclusions: Caffeine significantly inhibited acetaldehyde-induced HSC-T6 cells activation by distinct A2AR mediated signal pathway via inhibition of cAMP-PKA-SRC-ERK1/2 for procollagen type I and via P38 MAPK for procollagen type III. PMID:24682220

  3. Malondialdehyde-Acetaldehyde (MAA) Adducted Surfactant Protein Alters Macrophage Functions through Scavenger Receptor A

    PubMed Central

    Sapkota, Muna; Kharbanda, Kusum K.; Wyatt, Todd A.

    2016-01-01

    Background Reactive aldehydes like acetaldehyde and malondialdehyde generated as a result of alcohol metabolism and cigarette smoke exposure lead to the formation of malondialdehyde-acetaldehyde-adducted proteins (MAA adducts). These aldehydes can adduct to different proteins such as bovine serum album (BSA) and surfactant proteins A or D (SPA, SPD). Macrophages play an important role in innate immunity, but the effect of MAA adducts on macrophage function has not yet been examined. Because macrophage scavenger receptor A (SRA; CD204) mediates the uptake of modified proteins, we hypothesized that the effects of MAA modified proteins on macrophage function are primarily mediated through SRA. Methods and Results We tested this hypothesis by exposing SPD-MAA to macrophages and measuring functions. SPD-MAA treatment significantly stimulated pro-inflammatory cytokine TNF-α release in the macrophage cell line, RAW 264.7. A significant reduction in phagocytosis of zymosan particles was also observed. SPD-MAA stimulated a significant dose-dependent increase in TNF-α and IL-6 release from peritoneal macrophages of WT mice. But a significantly less TNF-α and IL-6 were released from peritoneal macrophages of SRA−/− mice. We observed a significant reduction in phagocytosis of zymosan particles in peritoneal macrophages from WT mice treated with SPD-MAA. No further SPD-MAA-induced reduction was seen in peritoneal macrophages form SRA−/− mice. SPD-MAA treatment significantly increased SRA mRNA expression, but had no effect on surface receptor protein expression. Protein kinase C alpha inhibitor and NF-κB inhibitor significantly reduced pro-inflammatory cytokine release in response to SPD-MAA. Conclusion In conclusion, our data demonstrate that SRA is important for MAA-adducted protein-mediated effect on macrophage functions. PMID:27783409

  4. Acetaldehyde dissociates the PTP1B–E-cadherin–β-catenin complex in Caco-2 cell monolayers by a phosphorylation-dependent mechanism

    PubMed Central

    Sheth, Parimal; Seth, Ankur; Atkinson, Katherine J.; Gheyi, Tarun; Kale, Gautam; Giorgianni, Francesco; Desiderio, Dominic M.; Li, Chunying; Naren, Anjaparavanda; Rao, Radhakrishna

    2006-01-01

    Interactions between E-cadherin, β-catenin and PTP1B (protein tyrosine phosphatase 1B) are crucial for the organization of AJs (adherens junctions) and epithelial cell–cell adhesion. In the present study, the effect of acetaldehyde on the AJs and on the interactions between E-cadherin, β-catenin and PTP1B was determined in Caco-2 cell monolayers. Treatment of cell monolayers with acetaldehyde induced redistribution of E-cadherin and β-catenin from the intercellular junctions by a tyrosine phosphorylation-dependent mechanism. The PTPase activity associated with E-cadherin and β-catenin was significantly reduced and the interaction of PTP1B with E-cadherin and β-catenin was attenuated by acetaldehyde. Acetaldehyde treatment resulted in phosphorylation of β-catenin on tyrosine residues, and abolished the interaction of β-catenin with E-cadherin by a tyrosine kinase-dependent mechanism. Protein binding studies showed that the treatment of cells with acetaldehyde reduced the binding of β-catenin to the C-terminal region of E-cadherin. Pairwise binding studies using purified proteins indicated that the direct interaction between E-cadherin and β-catenin was reduced by tyrosine phosphorylation of β-catenin, but was unaffected by tyrosine phosphorylation of E-cadherin-C. Treatment of cells with acetaldehyde also reduced the binding of E-cadherin to GST (glutathione S-transferase)–PTP1B. The pairwise binding study showed that GST–E-cadherin-C binds to recombinant PTP1B, but this binding was significantly reduced by tyrosine phosphorylation of E-cadherin. Acetaldehyde increased the phosphorylation of β-catenin on Tyr-331, Tyr-333, Tyr-654 and Tyr-670. These results show that acetaldehyde induces disruption of interactions between E-cadherin, β-catenin and PTP1B by a phosphorylation-dependent mechanism. PMID:17087658

  5. Electrode Reactions Coupled with Chemical Reactions of Oxygen, Water and Acetaldehyde in an Ionic Liquid: New Approaches for Sensing Volatile Organic Compounds.

    PubMed

    Chi, Xiaowei; Tang, Yongan; Zeng, Xiangqun

    2016-10-20

    Water and oxygen are ubiquitous present in ambient conditions. This work studies the unique oxygen, trace water and a volatile organic compound (VOC) acetaldehyde redox chemistry in a hydrophobic and aprotic ionic liquid (IL), 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([Bmpy] [NTf 2 ]) by cyclic voltammetry and potential step methods. One electron oxygen reduction leads to superoxide radical formation in the IL. Trace water in the IL acts as a protic species that reacts with the superoxide radical. Acetaldehyde is a stronger protic species than water for reacting with the superoxide radical. The presence of trace water in the IL was also demonstrated to facilitate the electro-oxidation of acetaldehyde, with similar mechanism to that in the aqueous solutions. A multiple-step coupling reaction mechanism between water, superoxide radical and acetaldehyde has been described. The unique characteristics of redox chemistry of acetaldehyde in [Bmpy][NTf 2 ] in the presence of oxygen and trace water can be controlled by electrochemical potentials. By controlling the electrode potential windows, several methods including cyclic voltammetry, potential step methods (single-potential, double-potential and triple-potential step methods) were established for the quantification of acetaldehyde. Instead of treating water and oxygen as frustrating interferents to ILs, we found that oxygen and trace water chemistry in [Bmpy][NTf 2 ] can be utilized to develop innovative electrochemical methods for electroanalysis of acetaldehyde.

  6. Electrode Reactions Coupled with Chemical Reactions of Oxygen, Water and Acetaldehyde in an Ionic Liquid: New Approaches for Sensing Volatile Organic Compounds

    PubMed Central

    Chi, Xiaowei; Tang, Yongan; Zeng, Xiangqun

    2017-01-01

    Water and oxygen are ubiquitous present in ambient conditions. This work studies the unique oxygen, trace water and a volatile organic compound (VOC) acetaldehyde redox chemistry in a hydrophobic and aprotic ionic liquid (IL), 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([Bmpy] [NTf2]) by cyclic voltammetry and potential step methods. One electron oxygen reduction leads to superoxide radical formation in the IL. Trace water in the IL acts as a protic species that reacts with the superoxide radical. Acetaldehyde is a stronger protic species than water for reacting with the superoxide radical. The presence of trace water in the IL was also demonstrated to facilitate the electro-oxidation of acetaldehyde, with similar mechanism to that in the aqueous solutions. A multiple-step coupling reaction mechanism between water, superoxide radical and acetaldehyde has been described. The unique characteristics of redox chemistry of acetaldehyde in [Bmpy][NTf2] in the presence of oxygen and trace water can be controlled by electrochemical potentials. By controlling the electrode potential windows, several methods including cyclic voltammetry, potential step methods (single-potential, double-potential and triple-potential step methods) were established for the quantification of acetaldehyde. Instead of treating water and oxygen as frustrating interferents to ILs, we found that oxygen and trace water chemistry in [Bmpy][NTf2] can be utilized to develop innovative electrochemical methods for electroanalysis of acetaldehyde. PMID:29142331

  7. Method of acetaldehyde measurement with minimal artifactual formation in red blood cells and plasma of actively drinking subjects with alcoholism.

    PubMed

    Hernandez-Munoz, R; Ma, X L; Baraona, E; Lieber, C S

    1992-07-01

    After alcohol consumption, a substantial amount of acetaldehyde that is reversibly bound to protein and nonprotein components of the red blood cells circulates in the blood and could cause extrahepatic toxicity. However, acetaldehyde measurement in human red blood cells is hampered by considerable ex vivo artifactual formation as a result of nonenzymatic oxidation of ethanol during protein precipitation. To eliminate this source of artifactual formation, free and reversibly bound acetaldehyde were trapped with semicarbazide from red blood cell hemolysates, and both the stroma and the hemoglobin were sequentially removed by centrifugation and ion-exchange chromatography in carboxymethyl Sephadex, respectively. The eluted semi-carbazone was dissociated with perchloric acid, and the acetaldehyde that was released in the protein-free supernatants was measured by head-space gas chromatography. Maximal retention of hemoglobin by carboxymethyl Sephadex and complete recovery of acetaldehyde and ethanol were achieved at a pH of 5.3. The artifactual formation decreased from 2.62 +/- 0.32 mumol of acetaldehyde per millimole of ethanol in the initial hemolysates to 1.38 +/- 0.20 mumol after removal of the stroma and to a level that is comparable to measurements in plasma (0.09 +/- 0.02 mumol) after removal of both the stroma and the hemoglobin. In 12 actively drinking subjects with alcoholism, with blood ethanol levels that ranged between 9 and 81 mmol/L, the concentrations of acetaldehyde in red blood cells (11.50 +/- 1.46 mumol/L; range: 7.5 to 22 mumol/L) were minimally affected by blood ethanol levels and were three times as high as those in the plasma (3.74 +/- 1.49 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. BIOGENIC SOURCES OF FORMALDEHYDE AND ACETALDEHYDE DURING SUMMER AND WINTER CONDITIONS

    EPA Science Inventory

    Photochemical modeling estimated contributions to ambient concentrations of formaldehyde and acetaldehyde from biogenic emissions over the continental United States during January 2001 (Eos Trans. AGU, 83(47), Fall Meet. Suppl., Abstract A52B-0117). Results showed that maximum co...

  9. Mechanisms of Action of Acetaldehyde in the Up-Regulation of the Human α2(I) Collagen Gene in Hepatic Stellate Cells

    PubMed Central

    Reyes-Gordillo, Karina; Shah, Ruchi; Arellanes-Robledo, Jaime; Hernández-Nazara, Zamira; Rincón-Sánchez, Ana Rosa; Inagaki, Yutaka; Rojkind, Marcos; Lakshman, M. Raj

    2015-01-01

    Alcohol-induced liver fibrosis and eventually cirrhosis is a leading cause of death. Acetaldehyde, the first metabolite of ethanol, up-regulates expression of the human α2(I) collagen gene (COL1A2). Early acetaldehyde-mediated effects involve phosphorylation and nuclear translocation of SMAD3/4–containing complexes that bind to COL1A2 promoter to induce fibrogenesis. We used human and mouse hepatic stellate cells to elucidate the mechanisms whereby acetaldehyde up-regulates COL1A2 by modulating the role of Ski and the expression of SMADs 3, 4, and 7. Acetaldehyde induced up-regulation of COL1A2 by 3.5-fold, with concomitant increases in the mRNA (threefold) and protein (4.2- and 3.5-fold) levels of SMAD3 and SMAD4, respectively. It also caused a 60% decrease in SMAD7 expression. Ski, a member of the Ski/Sno oncogene family, is colocalized in the nucleus with SMAD4. Acetaldehyde induces translocation of Ski and SMAD4 to the cytoplasm, where Ski undergoes proteasomal degradation, as confirmed by the ability of the proteasomal inhibitor lactacystin to blunt up-regulation of acetaldehyde-dependent COL1A2, but not of the nonspecific fibronectin gene (FN1). We conclude that acetaldehyde up-regulates COL1A2 by enhancing expression of the transactivators SMAD3 and SMAD4 while inhibiting the repressor SMAD7, along with promoting Ski translocation from the nucleus to cytoplasm. We speculate that drugs that prevent proteasomal degradation of repressors targeting COL1A2 may have antifibrogenic properties. PMID:24641900

  10. Diffusion behaviour of the acetaldehyde scavenger 2-aminobenzamide in polyethylene terephthalate for beverage bottles

    PubMed Central

    Franz, Roland; Gmeiner, Margit; Gruner, Anita; Kemmer, Diana; Welle, Frank

    2016-01-01

    ABSTRACT Polyethylene terephthalate (PET) bottles are widely used as packaging material for natural mineral water. However, trace levels of acetaldehyde can migrate into natural mineral water during the shelf life and might influence the taste of the PET bottled water. 2-Aminobenzamide is widely used during PET bottle production as a scavenging agent for acetaldehyde. The aim of this study was the determination of the migration kinetics of 2-aminobenzamide into natural mineral water as well as into 20% ethanol. From the migration kinetics, the diffusion coefficients of 2-aminobenzamide in PET at 23 and 40°C were determined to be 4.2 × 10− 16 and 4.2 × 10− 15 cm2 s–1, respectively. The diffusion coefficient for 20% ethanol at 40°C was determined to be 7.7 × 10− 15 cm2 s–1, which indicates that 20% ethanol is causing swelling of the PET polymer. From a comparison of migration values between 23 and 40°C, acceleration factors of 9.7 when using water as contact medium and 18.1 for 20% ethanol as simulant can be derived for definition of appropriate accelerated test conditions at 40°C. The European Union regulatory acceleration test based on 80 kJ mol–1 as conservative activation energy overestimates the experimentally determined acceleration rates by a factor of 1.6 and 3.1, respectively. PMID:26666986

  11. On the Accuracy of In Vivo Ethanol and Acetaldehyde Monitoring, a Key Tile in the Puzzle of Acetaldehyde as a Neuroactive Agent.

    PubMed

    Enrico, Paolo; Diana, Marco

    2017-01-01

    Over the last 20 years researchers have explored the postulated role of acetaldehyde (ACD) as a mediator of some of the actions of ethanol (EtOH) in the central nervous system (CNS). However, efforts have been hampered mainly by the difficulty of directly measuring in vivo EtOH and ACD levels in the CNS and thus, our knowledge is based on indirect evidences. Although technically challenging, the development of reliable methods for in vivo measurement of ACD and EtOH is of paramount importance to solve the " puzzle of acetaldehyde as a neuroactive agent. " In this short review we discuss the recent advances on brain EtOH pharmacokinetic and state-of-the-art available techniques that could be used for in vivo detect EtOH and ACD both non-invasively (magnetic resonance spectroscopy), and invasively (microdialysis and biosensors). Among the different in vivo sampling techniques described, particular emphasis is paid to the field of enzyme-based amperometric biosensors. Biosensors have gained much attention in recent years for their ability to online monitor biological signals in vivo , and several micro- and nano-structured devices have been successfully used for in vivo studies. Owing to their high temporal and spatial resolution, biosensors could provide the adequate technology for studying in vivo EtOH pharmacokinetic.

  12. Impact of bioethanol fuel implementation in transport based on modelled acetaldehyde concentration in the urban environment.

    PubMed

    Sundvor, Ingrid; López-Aparicio, Susana

    2014-10-15

    This study shows the results obtained from emission and air dispersion modelling of acetaldehyde in the city of Oslo and associated with the circulation of bioethanol vehicles. Two scenarios of bioethanol implementation, both realistic and hypothetical, have been considered under winter conditions; 1) realistic baseline scenario, which corresponds to the current situation in Oslo where one bus line is running with bioethanol (E95; 95% ethanol-5% petrol) among petrol and diesel vehicles; and 2) a hypothetical scenario characterized by a full implementation of high-blend bioethanol (i.e. E85) as fuel for transportation, and thus an entire bioethanol fleet. The results indicate that a full implementation of bioethanol will have a certain impact on urban air quality due to direct emissions of acetaldehyde. Acetaldehyde emissions are estimated to increase by 233% and concentration levels increase up to 650% with regard to the baseline. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Bridging the Gap between Gene Expression and Metabolic Phenotype via Kinetic Models

    DTIC Science & Technology

    2013-07-22

    construction of large-scale kinetic models of metabolism, namely, the detailed definition of appro- priate reaction rate expressions and the determination...mole of bio- mass precursor, and the summation included only the drain fluxes to biomass. Note that this definition of the biomass growth rate can... 4P G ly co ly si s Glu Pro Arg Lys Glucose-6P Carbohydrates RNA Lipids Acetaldehyde Figure 2 Metabolic network of the central carbon

  14. Simultaneous determination of methanol, acetaldehyde, acetone, and ethanol in human blood by gas chromatography with flame ionization detection.

    PubMed

    Schlatter, J; Chiadmi, F; Gandon, V; Chariot, P

    2014-01-01

    Methanol, acetaldehyde, acetone, and ethanol, which are commonly used as biomarkers of several diseases, in acute intoxications, and forensic settings, can be detected and quantified in biological fluids. Gas chromatography (GC)-mass spectrometry techniques are complex, require highly trained personnel and expensive materials. Gas chromatographic determinations of ethanol, methanol, and acetone have been reported in one study with suboptimal accuracy. Our objective was to improve the assessment of these compounds in human blood using GC with flame ionization detection. An amount of 50 µl of blood was diluted with 300 µl of sterile water, 40 µl of 10% sodium tungstate, and 20 µl of 1% sulphuric acid. After centrifugation, 1 µl of the supernatant was injected into the gas chromatograph. We used a dimethylpolysiloxane capillary column of 30 m × 0.25 mm × 0.25 µm. We observed linear correlations from 7.5 to 240 mg/l for methanol, acetaldehyde, and acetone and from 75 to 2400 mg/l for ethanol. Precision at concentrations 15, 60, and 120 mg/l for methanol, acetaldehyde, and acetone and 150, 600, and 1200 mg/ml for ethanol were 0.8-6.9%. Ranges of accuracy were 94.7-98.9% for methanol, 91.2-97.4% for acetaldehyde, 96.1-98.7% for acetone, and 105.5-111.6% for ethanol. Limits of detection were 0.80 mg/l for methanol, 0.61 mg/l for acetaldehyde, 0.58 mg/l for acetone, and 0.53 mg/l for ethanol. This method is suitable for routine clinical and forensic practices.

  15. The influence of calcination temperatures on the acid-based properties and catalytic activity for the 1,3-butadiene synthesis from ethanol/acetaldehyde mixture

    NASA Astrophysics Data System (ADS)

    Gao, Meixiang; Jiang, Haoxi; Zhang, Minhua

    2018-05-01

    The influences of the calcination temperature on the catalysts' acid-based properties and catalytic activity for the 1,3-butadiene synthesis from ethanol are investigated. The results show that the 2 wt% ZrO2/Nano-SiO2 calcined at 773 K shows the best performance with the selectivity of 93.18% and conversion of 58.52% when reacted at 593 K, a WHSV of 1.8 h-1 and 3.5:1 volume ratio ethanol-to-acetaldehyde in an atmospheric fixed-bed reactor. Prepared catalysts were characterized by N2 adsorption-desorption, XRD, temperature-programmed desorption of NH3 and CO2, FTIR spectroscopy of adsorbed pyridine and CO2. Based on the relationship between the catalyst activity and its properties, the fact can be presumed that the formation and strength of Zrsbnd Osbnd Si bond determines the acid-based properties of the catalyst. In addition, moderate-intensity weak acid-basic sites are more suitable for ethanol conversion to BD with the amount of acid and basic sites as close as possible.

  16. Characterization of the increased binding of acetaldehyde to red blood cells in alcoholics.

    PubMed

    Hernández-Muñoz, R; Baraona, E; Blacksberg, I; Lieber, C S

    1989-10-01

    Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N-ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and Bmax were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by N-ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein-free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.

  17. Regional Sources of Atmospheric Formaldehyde and Acetaldehyde, and Implications for Atmospheric Modeling

    EPA Science Inventory

    Formaldehyde and acetaldehyde concentrations over the Eastern half of the United States are simulated with a 3-D air quality model to identify the most important chemical precursors under January and July conditions. We find that both aldehydes primarily result from photochemical...

  18. Toluene and acetaldehyde removal from air on to graphene-based adsorbents with microsized pores.

    PubMed

    Kim, Ji Min; Kim, Ji Hoon; Lee, Chang Yeon; Jerng, Dong Wook; Ahn, Ho Seon

    2018-02-15

    Volatile organic compound (VOC) gases can cause harm to the human body with exposure over the long term even at very low concentrations (ppmv levels); thus, effective absorbents for VOC gas removal are an important issue. In this study, accordingly, graphene-based adsorbents with microsized pores were used as adsorbents to remove toluene and acetaldehyde gases at low concentrations (30ppm). Sufficient amounts of the adsorbents were prepared for use on filters and were loaded uniformly at 0.1-0.5g on a 50×50mm 2 area, to evaluate their adsorption features with low gas concentrations. The morphology and chemical composition of the adsorbents were characterized using scanning electron microscopy, N 2 adsorption-desorption isotherms, X-ray photoelectron spectroscopy, and Raman spectroscopy. Microwave irradiation and heat treatment near 800°C under KOH activation resulted in enlargement of the pristine graphene surface and its specific surface area; maximum volume capacities of 3510m 3 /g and 630m 3 /g were observed for toluene and acetaldehyde gas. The high removal efficiency for toluene (98%) versus acetaldehyde (30%) gas was attributed to π-π interactions between the pristine graphene surface and toluene molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Quantitative Determination of Acetaldehyde in Foods Using Automated Digestion with Simulated Gastric Fluid Followed by Headspace Gas Chromatography

    PubMed Central

    Uebelacker, Michael; Lachenmeier, Dirk W.

    2011-01-01

    Acetaldehyde (ethanal) is a genotoxic carcinogen, which may occur naturally or as an added flavour in foods. We have developed an efficient method to analyze the compound in a wide variety of food matrices. The analysis is conducted using headspace (HS) gas chromatography (GC) with flame ionization detector. Using a robot autosampler, the samples are digested in full automation with simulated gastric fluid (1 h at 37°C) under shaking, which frees acetaldehyde loosely bound to matrix compounds. Afterwards, an aliquot of the HS is injected into the GC system. Standard addition was applied for quantification to compensate for matrix effects. The precision of the method was sufficient (<3% coefficient of variation). The limit of detection was 0.01 mg/L and the limit of quantification was 0.04 mg/L. 140 authentic samples were analyzed. The acetaldehyde content in apples was 0.97 ± 0.80 mg/kg, orange juice contained 3.86 ± 2.88 mg/kg. The highest concentration was determined in a yoghurt (17 mg/kg). A first-exposure estimation resulted in a daily acetaldehyde intake of less than 0.1 mg/kg bodyweight from food, which is considerably lower than the exposures from alcohol consumption or tobacco smoking. PMID:21747735

  20. Effects of 20 Selected Fruits on Ethanol Metabolism: Potential Health Benefits and Harmful Impacts

    PubMed Central

    Zhang, Yu-Jie; Wang, Fang; Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Zhang, Jiao-Jiao; Li, Sha; Xu, Dong-Ping; Li, Hua-Bin

    2016-01-01

    The consumption of alcohol is often accompanied by other foods, such as fruits and vegetables. This study is aimed to investigate the effects of 20 selected fruits on ethanol metabolism to find out their potential health benefits and harmful impacts. The effects of the fruits on ethanol metabolism were characterized by the concentrations of ethanol and acetaldehyde in blood, as well as activities of alcohol dehydrogenase and acetaldehyde dehydrogenase in liver of mice. Furthermore, potential health benefits and harmful impacts of the fruits were evaluated by biochemical parameters including aspartate transaminase (AST), alanine transferase (ALT), malondialdehyde, and superoxide dismutase. Generally, effects of these fruits on ethanol metabolism were very different. Some fruits (such as Citrus limon (yellow), Averrhoa carambola, Pyrus spp., and Syzygium samarangense) could decrease the concentration of ethanol in blood. In addition, several fruits (such as Cucumis melo) showed hepatoprotective effects by significantly decreasing AST or ALT level in blood, while some fruits (such as Averrhoa carambola) showed adverse effects. The results suggested that the consumption of alcohol should not be accompanied by some fruits, and several fruits could be developed as functional foods for the prevention and treatment of hangover and alcohol use disorder. PMID:27043608

  1. Effects of 20 Selected Fruits on Ethanol Metabolism: Potential Health Benefits and Harmful Impacts.

    PubMed

    Zhang, Yu-Jie; Wang, Fang; Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Zhang, Jiao-Jiao; Li, Sha; Xu, Dong-Ping; Li, Hua-Bin

    2016-04-01

    The consumption of alcohol is often accompanied by other foods, such as fruits and vegetables. This study is aimed to investigate the effects of 20 selected fruits on ethanol metabolism to find out their potential health benefits and harmful impacts. The effects of the fruits on ethanol metabolism were characterized by the concentrations of ethanol and acetaldehyde in blood, as well as activities of alcohol dehydrogenase and acetaldehyde dehydrogenase in liver of mice. Furthermore, potential health benefits and harmful impacts of the fruits were evaluated by biochemical parameters including aspartate transaminase (AST), alanine transferase (ALT), malondialdehyde, and superoxide dismutase. Generally, effects of these fruits on ethanol metabolism were very different. Some fruits (such as Citrus limon (yellow), Averrhoa carambola, Pyrus spp., and Syzygium samarangense) could decrease the concentration of ethanol in blood. In addition, several fruits (such as Cucumis melo) showed hepatoprotective effects by significantly decreasing AST or ALT level in blood, while some fruits (such as Averrhoa carambola) showed adverse effects. The results suggested that the consumption of alcohol should not be accompanied by some fruits, and several fruits could be developed as functional foods for the prevention and treatment of hangover and alcohol use disorder.

  2. Formation of the thioester, N,S-diacetylcysteine, from acetaldehyde and N,N'-diacetylcystine in aqueous solution with ultraviolet light

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    1981-01-01

    The thioester, N,S-diacetylcysteine, is formed during the illumination of phosphate buffered (pH 7.0) aqueous solutions of acetaldehyde and N,N'-diacetylcystine with ultraviolet light. The yield of N,S-diacetylcysteine relative to N-acetylcysteine and unidentified products progressively increases as ultraviolet light below 239 nm, 253 nm and 281 nm is cut off with optical filters. When ultraviolet light below 320 nm is removed with an optical filter, there is no detectable reaction. Illumination of 0.025 M N,N'-diacetylcystine with 0.5 M and 1.0 M acetaldehyde with filtered ultraviolet light gives, respectively, 20% and 80% yields of N,S-diacetylcysteine. In the reaction with 1.0 M acetaldehyde, N-acetylcysteine forms early in the reaction and later decreases with its conversion to N,S-diacetylcysteine. The prebiotic significance of these reactions is discussed.

  3. Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways.

    PubMed

    Hagland, Hanne R; Søreide, Kjetil

    2015-01-28

    The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  4. Evaluating acetaldehyde synthesis from L-/sup 14/C(U)) threonine by Streptococcus thermophilus and Lactobacillus bulgaricus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilkins, D.W.; Schmidt, R.H.; Shireman, R.B.

    To evaluate the synthesis of acetaldehyde from threonine during growth of yogurt cultures, Streptococcus thermophilus MS1 and Lactobacillus bulgaricus MR1 were grown in defined medium in which 10% of the total threonine was composed of L-(carbon-14(U))threonine. Acetaldehyde production was monitored by formation of 2,4-dinitrophenylhydrazone followed by separation and analysis using high performance liquid chromatography. After growth for 8 h at 42/sup 0/C, approximately 2.0% of the total acetaldehyde (780.4 nmol) produced was from L-(carbon-14)threonine. Threonine aldolase activity was determined in cell-free extracts from S. thermophilus and L. bulgaricus grown in Elliker broth. Increasing incubation temperature from 30 to 42/sup 0/Cmore » decreased threonine aldolase activity in cells of the streptococcus harvested after 8 h of incubation. Effect of incubation temperature was more dramatic in cells harvested after 18 h where the activity of cells grown at 48/sup 0/C was 89% lower than that of cells grown at 30/sup 0/C. Cell extracts from S. thermophilus MS1 possessed higher threonine aldolase activity than did those from L. bulgaricus MR1. Increased assay temperature from 30 to 42/sup 0/C increased threonine aldolase activity in S. thermophilus MS1.« less

  5. Catalytic Upgrading of Biomass-Derived Compounds via C-C Coupling Reactions. Computational and Experimental Studies of Acetaldehyde and Furan Reactions in HZSM-5

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Cong; Evans, Tabitha J.; Cheng, Lei

    2015-10-02

    These catalytic C–C coupling and deoxygenation reactions are essential for upgrading of biomass-derived oxygenates to fuel-range hydrocarbons. Detailed understanding of mechanistic and energetic aspects of these reactions is crucial to enabling and improving the catalytic upgrading of small oxygenates to useful chemicals and fuels. Using periodic density functional theory (DFT) calculations, we have investigated the reactions of furan and acetaldehyde in an HZSM-5 zeolite catalyst, a representative system associated with the catalytic upgrading of pyrolysis vapors. Comprehensive energy profiles were computed for self-reactions (i.e., acetaldehyde coupling and furan coupling) and cross-reactions (i.e., acetaldehyde + furan) of this representative mixture. Majormore » products proposed from the computations are further confirmed using temperature controlled mass spectra measurements. Moreover, the computational results show that furan interacts with acetaldehyde in HZSM-5 via an alkylation mechanism, which is more favorable than the self-reactions, indicating that mixing furans with aldehydes could be a promising approach to maximize effective C–C coupling and dehydration while reducing the catalyst deactivation (e.g., coke formation) from aldehyde condensation.« less

  6. Mass-Specific Metabolic Rate Influences Sperm Performance through Energy Production in Mammals

    PubMed Central

    Tourmente, Maximiliano; Roldan, Eduardo R. S.

    2015-01-01

    Mass-specific metabolic rate, the rate at which organisms consume energy per gram of body weight, is negatively associated with body size in metazoans. As a consequence, small species have higher cellular metabolic rates and are able to process resources at a faster rate than large species. Since mass-specific metabolic rate has been shown to constrain evolution of sperm traits, and most of the metabolic activity of sperm cells relates to ATP production for sperm motility, we hypothesized that mass-specific metabolic rate could influence sperm energetic metabolism at the cellular level if sperm cells maintain the metabolic rate of organisms that generate them. We compared data on sperm straight-line velocity, mass-specific metabolic rate, and sperm ATP content from 40 mammalian species and found that the mass-specific metabolic rate positively influences sperm swimming velocity by (a) an indirect effect of sperm as the result of an increased sperm length, and (b) a direct effect independent of sperm length. In addition, our analyses show that species with higher mass-specific metabolic rate have higher ATP content per sperm and higher concentration of ATP per μm of sperm length, which are positively associated with sperm velocity. In conclusion, our results suggest that species with high mass-specific metabolic rate have been able to evolve both long and fast sperm. Moreover, independently of its effect on the production of larger sperm, the mass-specific metabolic rate is able to influence sperm velocity by increasing sperm ATP content in mammals. PMID:26371474

  7. Resolving Some Paradoxes in the Thermal Decomposition Mechanism of Acetaldehyde

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sivaramakrishnan, Raghu; Michael, Joe V.; Harding, Lawrence B.

    2015-07-16

    The mechanism for the thermal decomposition of acetaldehyde has been revisited with an analysis of literature kinetics experiments using theoretical kinetics. The present modeling study was motivated by recent observations, with very sensitive diagnostics, of some unexpected products in high temperature micro-tubular reactor experiments on the thermal decomposition of CH3CHO and its deuterated analogs, CH3CDO, CD3CHO, and CD3CDO. The observations of these products prompted the authors of these studies to suggest that the enol tautomer, CH2CHOH (vinyl alcohol), is a primary intermediate in the thermal decomposition of acetaldehyde. The present modeling efforts on acetaldehyde decomposition incorporate a master equation re-analysismore » of the CH3CHO potential energy surface (PES). The lowest energy process on this PES is an isomerization of CH3CHO to CH2CHOH. However, the subsequent product channels for CH2CHOH are substantially higher in energy, and the only unimolecular process that can be thermally accessed is a re-isomerization to CH3CHO. The incorporation of these new theoretical kinetics predictions into models for selected literature experiments on CH3CHO thermal decomposition confirms our earlier experiment and theory based conclusions that the dominant decomposition process in CH3CHO at high temperatures is C-C bond fission with a minor contribution (~10-20%) from the roaming mechanism to form CH4 and CO. The present modeling efforts also incorporate a master-equation analysis of the H + CH2CHOH potential energy surface. This bimolecular reaction is the primary mechanism for removal of CH2CHOH, which can accumulate to minor amounts at high temperatures, T > 1000 K, in most lab-scale experiments that use large initial concentrations of CH3CHO. Our modeling efforts indicate that the observation of ketene, water and acetylene in the recent micro-tubular experiments are primarily due to bimolecular reactions of CH3CHO and CH2CHOH with H-atoms, and have no

  8. Thz Spectroscopy of 13C Isotopic Species of a "weed": Acetaldehyde

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Guillemin, J.-C.

    2011-06-01

    Our studies of the isotopic species of 13C and D isotopologues of methyl formate (HCOOCH_3), have allowed the detection of more than 600 lines in Orion. This confirms that many observed U-lines are coming from isotopic species of one of the most abundant molecules in space. Since its first detection in 1976 in SgrB2 and in Orion A, acetaldehyde (CH_3CHO) was detected in many other numerous objects. If its deuterated species (CD_3CHO and CH_3CDO) have been previously studied in the millimeterwave range, the data concerning the 13C species are limited to few lines measured in 1957 up to 40 GHz. In this context we decided to study the 13C species of acetaldehyde. Acetaldehyde molecule displays a large amplitude motion: the hindered rotation of the methyl group with respect to the rest of the molecule. The analysis is performed with the Rho Axis Method. Recent versions of the codes include high orders term in order to reproduce the observed frequencies for large quantum numbers values as J-values as high as 70a,b,. Measurements and analysis of the rotational spectra of 13C isotopic species are in progress in Lille with a solid-state submillimetre-wave spectrometer (50-950 GHz), the first results will be presented. This work is supported by the contract ANR-08-BLAN-0054 and by the Programme National de Physico-Chimie du Milieu Interstellaire (PCMI-CNRS). Carvajal, M.; Margulès, L.; Tercero, B.; et al.A&A 500, (2009) 1109 Margulès, L.; Huet, T. R.; Demaison J.; et al.,ApJ 714, (2010) 1120. Ikeda, M.; Ohishi, M.; Nummelin, A.; et al., ApJ, 560, (2001) 792 Kleiner, I.; Lopez, J.-C.; Blanco, S.; et al.J. Mol. Spectrosc. 197, (1999) 275 Elkeurti M.; Coudert, L. H.; Medvedev, I. R.; et al.J. Mol. Spectrosc. 263, (2010) 145 Kilb, R.W.; Lin, C.C.; and Wilson, E.B.J. Chem. Phys. 26, (1957) 1695 Kleiner, I. J. Mol. Spectrosc. 260, (2010) 1 Ilyushin, V.V.; Kryvda, A; and Alekseev, E;J. Mol. Spectrosc. 255, (2009) 32

  9. Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

    PubMed

    Na, Hye-Kyung; Lee, Ja Young

    2017-05-24

    Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

  10. Uptake of acetaldehyde-modified (ethylated) low-density lipoproteins by mouse peritoneal macrophages.

    PubMed

    Wehr, Hanna; Mirkiewicz, Ewa; Rodo, Maria; Bednarska-Makaruk, Malgorzata

    2002-04-01

    The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs) by murine peritoneal macrophages is described and compared with the uptake of acetylated LDLs. The fluorescent marker DiI was used. No competition between ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not inhibited by polyinosinic acid or fucoidin. Our conclusion is that uptake of ethylated and acetylated LDLs can be done by two different receptors.

  11. Influence of host seed on metabolic activity by Enterobacter cloacae in the spermosphere

    USDA-ARS?s Scientific Manuscript database

    Little is known regarding the influences of nutrients released from plants on the metabolic activity of colonizing microbes. To gain a better understanding of these influences, we used bioluminescence- and oxygen consumption-based methods to compare bacterial metabolic activity expressed during col...

  12. The effect of SO2 on the production of ethanol, acetaldehyde, organic acids, and flavor volatiles during industrial cider fermentation.

    PubMed

    Herrero, Mónica; García, Luis A; Díaz, Mario

    2003-05-21

    SO(2) is widely used in cider fermentation but also in other alcoholic beverages such as wine. Although the authorized limit is 200 ppm total SO(2), the International Organizations recommend its total elimination or at least reduction due to health concerns. Addition of SO(2) to apple juice at levels frequently used in industrial cidermaking (100 mg/L) induced significantly higher acetaldehyde production by yeast than that obtained without SO(2). Although the practical implications of acetaldehyde evolution under cidermaking conditions has been overcome by research and few data are available, this compound reached levels in two 2000 L bioreactors that may have prevented the occurrence of simultaneous alcoholic and malolactic fermentation. It was observed that malolactic fermentation had a positive effect promoting reduction of acetaldehyde levels in cider fermented with juice, SO(2)-treated or not. The addition of SO(2) clearly delayed malolactic fermentation comparing to the control, affecting not the onset of the malolactic fermentation but the rate of malic acid degradation. This compound, however, had a stimulatory effect on alcoholic fermentation.

  13. Ginsenoside-free molecules from steam-dried ginseng berry promote ethanol metabolism: an alternative choice for an alcohol hangover.

    PubMed

    Lee, Do Ik; Kim, Seung Tae; Lee, Dong Hoon; Yu, Jung Min; Jang, Su Kil; Joo, Seong Soo

    2014-07-01

    Ethanol metabolism produces harmful compounds that contribute to liver damage and cause an alcohol hangover. The intermediate metabolite acetaldehyde is responsible for alcohol hangover and CYP2E1-induced reactive oxygen species damage liver tissues. In this study, we examined whether ginsenoside-free molecules (GFMs) from steam-dried ginseng berries promote ethanol metabolism and scavenge free radicals by stimulating primary enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, CYP2E1, and catalase) and antioxidant effects using in vitro and in vivo models. The results revealed that GFM effectively scavenged 2,2-diphenyl-1-picrylhydrazyl hydrate radicals and hydroxyl radicals. Notably, GFM significantly enhanced the expression of primary enzymes within 2 h in HepG2 cells. GFM clearly removed the consumed ethanol and significantly reduced the level of acetaldehyde as well as enhancement of primary gene expression in BALB/c mice. Moreover, GFM successfully protected HepG2 cells from ethanol attack. Of the major components identified in GFM, it was believed that linoleic acid was the most active ingredient. Based on these findings, we conclude that GFM holds promise for use as a new candidate for ethanol metabolism and as an antihangover agent. © 2014 Institute of Food Technologists®

  14. Oral Microbiome Metabolism: From "Who Are They?" to "What Are They Doing?".

    PubMed

    Takahashi, N

    2015-12-01

    Recent advances in molecular biology have facilitated analyses of the oral microbiome ("Who are they?"); however, its functions (e.g., metabolic activities) are poorly understood ("What are they doing?"). This review aims to summarize our current understanding of the metabolism of the oral microbiome. Saccharolytic bacteria-including Streptococcus, Actinomyces, and Lactobacillus species-degrade carbohydrates into organic acids via the Embden-Meyerhof-Parnas pathway and several of its branch pathways, resulting in dental caries, while alkalization and acid neutralization via the arginine deiminase system, urease, and so on, counteract acidification. Proteolytic/amino acid-degrading bacteria, including Prevotella and Porphyromonas species, break down proteins and peptides into amino acids and degrade them further via specific pathways to produce short-chain fatty acids, ammonia, sulfur compounds, and indole/skatole, which act as virulent and modifying factors in periodontitis and oral malodor. Furthermore, it is suggested that ethanol-derived acetaldehyde can cause oral cancer, while nitrate-derived nitrite can aid caries prevention and systemic health. Microbial metabolic activity is influenced by the oral environment; however, it can also modify the oral environment, enhance the pathogenicity of bacteria, and induce microbial selection to create more pathogenic microbiome. Taking a metabolomic approach to analyzing the oral microbiome is crucial to improving our understanding of the functions of the oral microbiome. © International & American Associations for Dental Research 2015.

  15. Malondialdehyde-Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies.

    PubMed

    Sapkota, Muna; Burnham, Ellen L; DeVasure, Jane M; Sweeter, Jenea M; Hunter, Carlos D; Duryee, Michael J; Klassen, Lynell W; Kharbanda, Kusum K; Sisson, Joseph H; Thiele, Geoffrey M; Wyatt, Todd A

    2017-12-01

    Malondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUDs) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde-acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodies. Four groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (-AUD/+smoke), AUD without smoke (+AUD/-smoke), and non-AUD/nonsmokers (-AUD/-smoke). We observed a significant increase in MAA adducts in lung cells of +AUD/+smoke versus -AUD/-smoke. No significant increase in MAA adducts was observed in -AUD/+smoke or in +AUD/-smoke compared to -AUD/-smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After 1 week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking. Copyright © 2017 by the Research Society on Alcoholism.

  16. Prevalence and Influencing Factors of Metabolic Syndrome Among Persons with Physical Disabilities.

    PubMed

    Jeong, Jeonghee; Yu, Jungok

    2018-03-01

    Metabolic syndrome is an important cluster of coronary heart disease risk factors. However, it remains unclear to what extent metabolic syndrome is associated with demographic and potentially modifiable lifestyle factors among Korean persons with physical disabilities. This study aimed to determine the prevalence and influencing factors of metabolic syndrome among persons with physical disabilities using the Korean National Health Insurance Service-National Sample Cohort. The Adult Treatment Panel III criteria were used to define metabolic syndrome influencing factors and prevalence, which were evaluated in a representative sample from the 2013 Korean National Health Insurance Service-National Sample Cohort database. Characteristics were compared based on frequency using the χ 2 test. The associations between metabolic syndrome and its risk factors were estimated using logistic multivariable regression analysis. Metabolic syndrome was detected in 31.5% of the surveyed persons with physical disabilities. Female sex, age of ≥65 years, smoking, greater alcohol consumption, physical inactivity, higher body mass index, and a family history of diabetes were associated with increased risks of metabolic syndrome. The major risk factors for metabolic syndrome among persons with physical disabilities were obesity and older age. Performing physical activity was associated with a lower risk of metabolic syndrome. Therefore, we recommend using a continuous obesity management program and physical activity to prevent metabolic syndrome among persons with physical disabilities. Copyright © 2018. Published by Elsevier B.V.

  17. A replaceable dual-enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate.

    PubMed

    Shi, Jing; Zhao, Wenwen; Chen, Yuanfang; Guo, Liping; Yang, Li

    2012-07-01

    A novel replaceable dual-enzyme capillary microreactor was developed and evaluated using magnetic fields to immobilize the alcohol dehydrogenase (ADH)- and lactate dehydrogenase (LDH)-coated magnetic beads at desired positions in the capillary. The dual-enzyme assay was achieved by measuring the two consumption peaks of the coenzyme β-nicotinamide adenine dinucleotide (NADH), which were related to the ADH reaction and LDH reaction. The dual-enzyme capillary microreactor was constructed using magnetic beads without any modification of the inner surface of the capillary, and showed great stability and reproducibility. The electrophoretic resolution for different analytes can be easily controlled by altering the relative distance of different enzyme-coated magnetic beads. The apparent K(m) values for acetaldehyde with ADH-catalyzed reaction and for pyruvate with LDH-catalyzed reaction were determined. The detection limits for acetaldehyde and pyruvate determination are 0.01 and 0.016 mM (S/N = 3), respectively. The proposed method was successfully applied to simultaneously determine the acetaldehyde and pyruvate contents in beer samples. The results indicated that combing magnetic beads with CE is of great value to perform replaceable and controllable multienzyme capillary microreactor for investigation of a series of enzyme reactions and determination of multisubstrates. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Molecular structure of the lithium enolate of acetaldehyde

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lynch, T.J.; Newcomb, M.; Bergbreiter, D.E.

    1980-11-21

    Calculations of the structures of isomers of the lithium enolate of acetaldehyde done at the restricted Hartree-Fock level with the HONDO program on the CDC 7600 are reported. Using the standard 4-31 G basis set, these calculations produce excessively large bond angles, and this favors the most open of the three isomeric structures. Including the polarization functions on the carbons and oxygen and using the recent Dunning and Hayes (3s2p/2s) contraction indicates that the chirol enolates are the lowest energy structure. However, the differences of the various enolate structures are small and could be modified by solvent effects. These resultsmore » are proported to suggest that the enolates containing internal ligands may be prepared such that a new chirol center would exist by virtue of the counterion position. (BLM)« less

  19. Protective effects of Lactococcus chungangensis CAU 28 on alcohol-metabolizing enzyme activity in rats.

    PubMed

    Konkit, Maytiya; Kim, Kiyoung; Kim, Jong-Hwa; Kim, Wonyong

    2018-04-19

    In this study, we investigated the beneficial effects of Lactococcus chungangensis CAU 28, a bacterial strain of nondairy origin, on alcohol metabolism in rats treated with ethanol, focusing on alcohol elimination and prevention of damage and comparing the effects with those observed for Lactococcus lactis ssp. lactis ATCC 19435. Male Sprague-Dawley rats were orally administered 20% ethanol and 3 substrates (freeze-dried cells, cream cheese, and yogurt) containing Lc. chungangensis CAU 28 or Lc. lactis ssp. lactis ATCC 19435, which were provided 1 h before or 1 h after ethanol ingestion. Blood samples were collected from the tail veins of the rats at 1, 3, 6, 12, and 24 h after ingestion of ethanol, Lc. chungangensis CAU 28 substrate, or Lc. lactis ssp. lactis ATCC 19435 substrate. Alcohol and acetaldehyde concentrations in the Lc. chungangensis CAU 28 substrate-treated rats were significantly reduced in a time-dependent manner compared with those in the Lc. lactis ssp. lactis ATCC 19435 substrate-treated rats. Among the experimental groups, treatment with cream cheese before ingestion of 20% ethanol was found to be the most effective method for reducing both alcohol and acetaldehyde levels in the blood. Alanine aminotransferase and aspartate aminotransferase activities in the Lc. chungangensis CAU 28 substrate-treated rats were significantly lower than those in the positive controls. Moreover, in the Lc. chungangensis CAU 28 cream cheese-treated group, rats showed a reduction of liver enzymes by up to 60%, with good effectiveness observed for both pre- and post-ethanol ingestion. These results suggested that intake of lactic acid bacteria, particularly in Lc. chungangensis CAU 28-supplemented dairy products, may reduce blood alcohol and acetaldehyde concentrations, thereby mitigating acute alcohol-induced hepatotoxicity by altering alcohol-metabolizing enzyme activities. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights

  20. The metabolism of ethanol-derived acetaldehyde by alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) in Drosophila melanogaster larvae.

    PubMed Central

    Heinstra, P W; Geer, B W; Seykens, D; Langevin, M

    1989-01-01

    Both aldehyde dehydrogenase (ALDH, EC 1.2.1.3) and the aldehyde dehydrogenase activity of alcohol dehydrogenase (ADH, EC 1.1.1.1) were found to coexist in Drosophila melanogaster larvae. The enzymes, however, showed different inhibition patterns with respect to pyrazole, cyanamide and disulphiram. ALDH-1 and ALDH-2 isoenzymes were detected in larvae by electrophoretic methods. Nonetheless, in tracer studies in vivo, more than 75% of the acetaldehyde converted to acetate by the ADH ethanol-degrading pathway appeared to be also catalysed by the ADH enzyme. The larval fat body probably was the major site of this pathway. Images Fig. 1. Fig. 2. PMID:2499314

  1. Acetaldehyde production by major oral microbes.

    PubMed

    Moritani, K; Takeshita, T; Shibata, Y; Ninomiya, T; Kiyohara, Y; Yamashita, Y

    2015-09-01

    To assess acetaldehyde (ACH) production by bacteria constituting the oral microbiota and the inhibitory effects of sugar alcohols on ACH production. The predominant bacterial components of the salivary microbiota of 166 orally healthy subjects were determined by barcoded pyrosequencing analysis of the 16S rRNA gene. Bacterial ACH production from ethanol or glucose was measured using gas chromatography. In addition, inhibition by four sugars and five sugar alcohols of ACH production was assayed. Forty-one species from 16 genera were selected as predominant and prevalent bacteria based on the following criteria: identification in ≥95% of the subjects, ≥1% of mean relative abundance or ≥5% of maximum relative abundance. All Neisseria species tested produced conspicuous amounts of ACH from ethanol, as did Rothia mucilaginosa, Streptococcus mitis and Prevotella histicola exhibited the ability to produce ACH. In addition, xylitol and sorbitol inhibited ACH production by Neisseria mucosa by more than 90%. The oral microbiota of orally healthy subjects comprises considerable amounts of bacteria possessing the ability to produce ACH, an oral carcinogen. Consumption of sugar alcohols may regulate ACH production by oral microbes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Mechanisms of action of acetaldehyde in the up-regulation of the human α2(I) collagen gene in hepatic stellate cells: key roles of Ski, SMAD3, SMAD4, and SMAD7.

    PubMed

    Reyes-Gordillo, Karina; Shah, Ruchi; Arellanes-Robledo, Jaime; Hernández-Nazara, Zamira; Rincón-Sánchez, Ana Rosa; Inagaki, Yutaka; Rojkind, Marcos; Lakshman, M Raj

    2014-05-01

    Alcohol-induced liver fibrosis and eventually cirrhosis is a leading cause of death. Acetaldehyde, the first metabolite of ethanol, up-regulates expression of the human α2(I) collagen gene (COL1A2). Early acetaldehyde-mediated effects involve phosphorylation and nuclear translocation of SMAD3/4-containing complexes that bind to COL1A2 promoter to induce fibrogenesis. We used human and mouse hepatic stellate cells to elucidate the mechanisms whereby acetaldehyde up-regulates COL1A2 by modulating the role of Ski and the expression of SMADs 3, 4, and 7. Acetaldehyde induced up-regulation of COL1A2 by 3.5-fold, with concomitant increases in the mRNA (threefold) and protein (4.2- and 3.5-fold) levels of SMAD3 and SMAD4, respectively. It also caused a 60% decrease in SMAD7 expression. Ski, a member of the Ski/Sno oncogene family, is colocalized in the nucleus with SMAD4. Acetaldehyde induces translocation of Ski and SMAD4 to the cytoplasm, where Ski undergoes proteasomal degradation, as confirmed by the ability of the proteasomal inhibitor lactacystin to blunt up-regulation of acetaldehyde-dependent COL1A2, but not of the nonspecific fibronectin gene (FN1). We conclude that acetaldehyde up-regulates COL1A2 by enhancing expression of the transactivators SMAD3 and SMAD4 while inhibiting the repressor SMAD7, along with promoting Ski translocation from the nucleus to cytoplasm. We speculate that drugs that prevent proteasomal degradation of repressors targeting COL1A2 may have antifibrogenic properties. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Identification of conjugate adducts formed in the reactions of malonaldehyde-acetaldehyde and malonaldehyde-formaldehyde with cytidine.

    PubMed

    Pluskota-Karwatka, Donata; Le Curieux, Frank; Munter, Tony; Sjöholm, Rainer; Kronberg, Leif

    2002-02-01

    Malonaldehyde was reacted with cytidine in buffered aqueous solutions in the presence of acetaldehyde or formaldehyde. The reaction mixtures were analyzed by HPLC, and the products were isolated by preparative C18 chromatography and structurally characterized by UV absorbance, fluorescence emission, (1)H and (13)C NMR spectroscopy, and mass spectrometry. The major adducts formed in the reaction of malonaldehyde and acetaldehyde were identified as 7-(beta-D-ribofuranosyl)-4-methyl-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde (M(1)AA-Cyd) and 1-(beta-D-ribofuranosyl)-4-(3,5-diformyl-4-methyl-1,4-dihydro-1-pyridyl)pyrimidine (M(2)AA-Cyd). In the reaction of malonaldehyde and formaldehyde, the major product was identified as 7-(beta-D-ribofuranosyl)-6-oxo-6,7-dihydro-4H-pyrimido[1,6-a]pyrimidine-3-carbaldehyde (M(1)FA-Cyd). The highest yields of M(1)AA-Cyd and M(2)AA-Cyd, 3.2 and 0.5 mol %, respectively, were obtained in the reaction performed at pH 4.6 and 37 degrees C for 8 days, while M(1)FA-Cyd was produced at a yield of 0.3 mol % after 3 days of reaction at pH 4.0 and 37 degrees C. The products consist of units derived from malonaldehyde and acetaldehyde (M(1)AA-Cyd and M(2)AA-Cyd) or from malonaldehyde and formaldehyde (M(1)FA-Cyd), and are thus further examples of nucleoside modifications containing structural elements derived from aldehyde condensation reactions. Trace amounts of the adducts may be formed at physiological conditions and may be involved in the mutagenicity of the studied aldehydes.

  4. Cattle temperament influences metabolism: 2. Metabolic response to an insulin sensivitiy test in beef steers

    USDA-ARS?s Scientific Manuscript database

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of non-esterified fatty acids (NEFAs) fou...

  5. Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina.

    PubMed

    Du, Jianhai; Rountree, Austin; Cleghorn, Whitney M; Contreras, Laura; Lindsay, Ken J; Sadilek, Martin; Gu, Haiwei; Djukovic, Danijel; Raftery, Dan; Satrústegui, Jorgina; Kanow, Mark; Chan, Lawrence; Tsang, Stephen H; Sweet, Ian R; Hurley, James B

    2016-02-26

    Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternatively, production can be set by a signal that anticipates demand. In this report we investigate the hypothesis that signaling through phototransduction controls production of energy in mouse retinas. We found that respiration in mouse retinas is not coupled tightly to ATP consumption. By analyzing metabolic flux in mouse retinas, we also found that phototransduction slows metabolic flux through glycolysis and through intermediates of the citric acid cycle. We also evaluated the relative contributions of regulation of the activities of α-ketoglutarate dehydrogenase and the aspartate-glutamate carrier 1. In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Synthesis and catalytic activity of electrospun NiO/NiCo2O4 nanotubes for CO and acetaldehyde oxidation

    NASA Astrophysics Data System (ADS)

    Kim, Il Hee; Lee, Hyerim; Yu, Areum; Jeong, Jae Hwan; Lee, Youngmi; Kim, Myung Hwa; Lee, Chongmok; Dok Kim, Young

    2018-04-01

    NiO/NiCo2O4 nanotubes with a diameter of approximately 100 nm are synthesized using Ni and Co precursors via electro-spinning and subsequent calcination processes. The tubular structure is confirmed via transmission electron microscopy imaging, whereas the structures and elemental compositions of the nanotubes are determined using x-ray diffraction, energy dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. N2 adsorption isotherm data reveal that the surface of the nanotubes consists of micropores, thereby resulting in a significantly higher surface area (˜20 m2 g-1) than expected for a flat-surface structure (<15 m2 g-1). Herein, we present a study of the catalytic activity of our novel NiO/NiCo2O4 nanotubes for CO and acetaldehyde oxidation. The catalytic activity of NiO/NiCo2O4 is superior to Pt below 100 °C for CO oxidation. For acetaldehyde oxidation, the total oxidation activity of NiO/NiCo2O4 for acetaldehyde is comparable with that of Pt. Coexistence of many under-coordinated Co and Ni active sites in our structure is suggested be related to the high catalytic activity. It is suggested that our novel NiO/NiCo2O4 tubular structures with surface microporosity can be of interest for a variety of applications, including the catalytic oxidation of harmful gases.

  7. Synthesis and catalytic activity of electrospun NiO/NiCo2O4 nanotubes for CO and acetaldehyde oxidation.

    PubMed

    Kim, Il Hee; Lee, Hyerim; Yu, Areum; Jeong, Jae Hwan; Lee, Youngmi; Kim, Myung Hwa; Lee, Chongmok; Kim, Young Dok

    2018-04-27

    NiO/NiCo 2 O 4 nanotubes with a diameter of approximately 100 nm are synthesized using Ni and Co precursors via electro-spinning and subsequent calcination processes. The tubular structure is confirmed via transmission electron microscopy imaging, whereas the structures and elemental compositions of the nanotubes are determined using x-ray diffraction, energy dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. N 2 adsorption isotherm data reveal that the surface of the nanotubes consists of micropores, thereby resulting in a significantly higher surface area (∼20 m 2 g -1 ) than expected for a flat-surface structure (<15 m 2 g -1 ). Herein, we present a study of the catalytic activity of our novel NiO/NiCo 2 O 4 nanotubes for CO and acetaldehyde oxidation. The catalytic activity of NiO/NiCo 2 O 4 is superior to Pt below 100 °C for CO oxidation. For acetaldehyde oxidation, the total oxidation activity of NiO/NiCo 2 O 4 for acetaldehyde is comparable with that of Pt. Coexistence of many under-coordinated Co and Ni active sites in our structure is suggested be related to the high catalytic activity. It is suggested that our novel NiO/NiCo 2 O 4 tubular structures with surface microporosity can be of interest for a variety of applications, including the catalytic oxidation of harmful gases.

  8. Malondialdehyde-acetaldehyde (MAA) adducted protein inhalation causes lung injury

    PubMed Central

    Wyatt, T. A.; Kharbanda, K. K.; McCaskill, M. L.; Tuma, D. J.; Yanov, D.; DeVasure, J.; Sisson, J. H.

    2011-01-01

    In addition to cigarette smoking, alcohol exposure is also associated with increased lung infections and decreased mucociliary clearance. However, little research has been conducted on the combination effects of alcohol and cigarette smoke on lungs. Previously, we have demonstrated in a mouse model that the combination of cigarette smoke and alcohol exposure results in the formation of a very stable hybrid malondialdehyde-acetaldehyde (MAA)-adducted protein in the lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial cell interleukin-8 via the activation of protein kinase C epsilon (PKCε). We hypothesized that direct MAA-adducted protein exposure in the lungs would mimic such a combination of smoke and alcohol exposure leading to airway inflammation. To test this hypothesis, C57BL/6J female mice were intranasally instilled with either saline, 30 µL of 50 µg/mL BSA-MAA, or unadducted BSA for up to 3 wk. Likewise, human lung surfactant proteins A and D (SPA, SPD) were purified from human pulmonary proteinosis lung lavage fluid and successfully MAA-adducted in vitro. Similar to BSA-MAA, SPD-MAA was instilled into mouse lungs. Lungs were necropsied and assayed for histopathology, PKCε activation, and lung lavage chemokines. In control mice instilled with saline, normal lungs had few inflammatory cells. No significant effects were observed in un-adducted BSA- or SPD-instilled mice. However, when mice were instilled with BSA-MAA or SPD-MAA for 3 wk, a significant peribronchiolar localization of inflammatory cells was observed. Both BSA-MAA and SPD-MAA stimulated increased lung lavage neutrophils and caused a significant elevation in the chemokine, KC, which is a functional homologue to human interleukin-8. Likewise, MAA-adducted protein stimulated the activation of airway and lung slice PKCε. These data support that MAA-adducted protein induces a pro-inflammatory response in the lungs and that lung surfactant protein is a biologically

  9. A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

    PubMed Central

    Nieminen, Mikko T.; Novak-Frazer, Lily; Rautemaa, Vilma; Rajendran, Ranjith; Sorsa, Timo; Ramage, Gordon; Bowyer, Paul; Rautemaa, Riina

    2014-01-01

    The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm

  10. The (impossible?) formation of acetaldehyde on the grain surfaces: insights from quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Enrique-Romero, J.; Rimola, A.; Ceccarelli, C.; Balucani, N.

    2016-06-01

    Complex Organic Molecules (COMs) have been detected in the interstellar medium (ISM). However, it is not clear whether their synthesis occurs on the icy surfaces of interstellar grains or via a series of gas-phase reactions. As a test case of the COMs synthesis in the ISM, we present new quantum chemical calculations on the formation of acetaldehyde (CH3CHO) from the coupling of the HCO and CH3 radicals, both in gas phase and on water ice surfaces. The binding energies of HCO and CH3 on the amorphous water ice were also computed (2333 and 734 K, respectively). Results indicate that, in gas phase, the products could be either CH3CHO, CH4 + CO, or CH3OCH, depending on the relative orientation of the two radicals. However, on the amorphous water ice, only the CH4 + CO product is possible due to the geometrical constraints imposed by the water ice surface. Therefore, acetaldehyde cannot be synthesized by the CH3 + HCO coupling on the icy grains. We discuss the implications of these results and other cases, such as ethylene glycol and dimethyl ether, in which similar situations can occur, suggesting that formation of these molecules on the grain surfaces might be unlikely.

  11. Role of alcohol dehydrogenase activity and the acetaldehyde in ethanol- induced ethane and pentane production by isolated perfused rat liver.

    PubMed Central

    Müller, A; Sies, H

    1982-01-01

    The volatile hydrocarbons ethane and n-pentane are produced at increased rates by isolated perfused rat liver during the metabolism of acutely ethanol. The effect is half-maximal at 0.5 mM-ethanol, and its is not observed when inhibitors of alcohol dehydrogenase such as 4-methyl- or 4-propyl-pyrazole are also present. Propanol, another substrate for the dehydrogenase, is also active. Increased alkane production can be initiated by adding acetaldehyde in the presence of 4-methyl- or 4-propyl-pyrazole. An antioxidant, cyanidanol, suppresses the ethanol-induced alkane production. The data obtained with the isolated organ demonstrate that products known to arise from the peroxidation of polyunsaturated fatty acids are formed in the presence of ethanol and that the activity of alcohol dehydrogenase is required for the generation of the active radical species. The mere presence of ethanol, e.g. at binding sites of special form(s) of cytochrome P-450, it not sufficient to elicit an increased production of volatile hydrocarbons by rat liver. PMID:6751324

  12. Flor yeasts of Saccharomyces cerevisiae--their ecology, genetics and metabolism.

    PubMed

    Alexandre, Hervé

    2013-10-15

    The aging of certain white wines is dependent on the presence of yeast strains that develop a biofilm on the wine surface after the alcoholic fermentation. These strains belong to the genus Saccharomyces and are called flor yeasts. These strains possess distinctive characteristics compared with Saccharomyces cerevisiae fermenting strain. The most important one is their capacity to form a biofilm on the air-liquid interface of the wine. The major gene involved in this phenotype is FLO11, however other genes are also involved in velum formation by these yeast and will be detailed. Other striking features presented in this review are their aneuploidy, and their mitochondrial DNA polymorphism which seems to reflect adaptive evolution of the yeast to a stressful environment where acetaldehyde and ethanol are present at elevated concentration. The biofilm assures access to oxygen and therefore permits continued growth on non-fermentable ethanol. This specific metabolism explains the peculiar organoleptic profile of these wines, especially their content in acetaldehyde and sotolon. This review deals with these different specificities of flor yeasts and will also underline the existing gaps regarding these astonishing yeasts. © 2013.

  13. Influence on bone metabolism of dietary trace elements, protein, fat, carbohydrates, and vitamins.

    PubMed

    Sarazin, M; Alexandre, C; Thomas, T

    2000-01-01

    Osteoporosis is a multifactorial disease driven primarily by the genetic factors that control bone metabolism. Among environmental factors, diet may play a key role, affording a target for low-cost intervention. Calcium and vitamin D are well known to affect bone metabolism. Other nutrients may influence bone mass changes; for instance, a number of trace elements and vitamins other than vitamin D are essential to many of the steps of bone metabolism. A wide variety of foods provide these nutrients, and in industrialized countries deficiencies are more often due to idiosyncratic eating habits than to cultural influences. Both culture and vogue influence the amount of carbohydrate, fat, and protein in the typical diet. In children, the current trend is to reduce protein and to increase carbohydrate and fat. Data from epidemiological and animal studies suggest that this may adversely affect bone mass and the fracture risk.

  14. Proteins involved in wine aroma compounds metabolism by a Saccharomyces cerevisiae flor-velum yeast strain grown in two conditions.

    PubMed

    Moreno-García, Jaime; García-Martínez, Teresa; Millán, M Carmen; Mauricio, Juan Carlos; Moreno, Juan

    2015-10-01

    A proteomic and exometabolomic study was conducted on Saccharomyces cerevisiae flor yeast strain growing under biofilm formation condition (BFC) with ethanol and glycerol as carbon sources and results were compared with those obtained under no biofilm formation condition (NBFC) containing glucose as carbon source. By using modern techniques, OFFGEL fractionator and LTQ-Orbitrap for proteome and SBSE-TD-GC-MS for metabolite analysis, we quantified 84 proteins including 33 directly involved in the metabolism of glycerol, ethanol and 17 aroma compounds. Contents in acetaldehyde, acetic acid, decanoic acid, 1,1-diethoxyethane, benzaldehyde and 2-phenethyl acetate, changed above their odor thresholds under BFC, and those of decanoic acid, ethyl octanoate, ethyl decanoate and isoamyl acetate under NBFC. Of the twenty proteins involved in the metabolism of ethanol, acetaldehyde, acetoin, 2,3-butanediol, 1,1-diethoxyethane, benzaldehyde, organic acids and ethyl esters, only Adh2p, Ald4p, Cys4p, Fas3p, Met2p and Plb1p were detected under BFC and as many Acs2p, Ald3p, Cem1p, Ilv2p, Ilv6p and Pox1p, only under NBFC. Of the eight proteins involved in glycerol metabolism, Gut2p was detected only under BFC while Pgs1p and Rhr2p were under NBFC. Finally, of the five proteins involved in the metabolism of higher alcohols, Thi3p was present under BFC, and Aro8p and Bat2p were under NBFC. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Sequence distribution of acetaldehyde-derived N2-ethyl-dG adducts along duplex DNA.

    PubMed

    Matter, Brock; Guza, Rebecca; Zhao, Jianwei; Li, Zhong-ze; Jones, Roger; Tretyakova, Natalia

    2007-10-01

    Acetaldehyde (AA) is the major metabolite of ethanol and may be responsible for an increased gastrointestinal cancer risk associated with alcohol beverage consumption. Furthermore, AA is one of the most abundant carcinogens in tobacco smoke and induces tumors of the respiratory tract in laboratory animals. AA binding to DNA induces Schiff base adducts at the exocyclic amino group of dG, N2-ethylidene-dG, which are reversible on the nucleoside level but can be stabilized by reduction to N2-ethyl-dG. Mutagenesis studies in the HPRT reporter gene and in the p53 tumor suppressor gene have revealed the ability of AA to induce G-->A transitions and A-->T transversions, as well as frameshift and splice mutations. AA-induced point mutations are most prominent at 5'-AGG-3' trinucleotides, possibly a result of sequence specific adduct formation, mispairing, and/or repair. However, DNA sequence preferences for the formation of acetaldehyde adducts have not been previously examined. In the present work, we employed a stable isotope labeling-HPLC-ESI+-MS/MS approach developed in our laboratory to analyze the distribution of acetaldehyde-derived N2-ethyl-dG adducts along double-stranded oligodeoxynucleotides representing two prominent lung cancer mutational "hotspots" and their surrounding DNA sequences. 1,7,NH 2-(15)N-2-(13)C-dG was placed at defined positions within DNA duplexes derived from the K-ras protooncogene and the p53 tumor suppressor gene, followed by AA treatment and NaBH 3CN reduction to convert N2-ethylidene-dG to N2-ethyl-dG. Capillary HPLC-ESI+-MS/MS was used to quantify N2-ethyl-dG adducts originating from the isotopically labeled and unlabeled guanine nucleobases and to map adduct formation along DNA duplexes. We found that the formation of N2-ethyl-dG adducts was only weakly affected by the local sequence context and was slightly increased in the presence of 5-methylcytosine within CG dinucleotides. These results are in contrast with sequence

  16. The influence of gut microbiota on drug metabolism and toxicity

    PubMed Central

    Li, Houkai; He, Jiaojiao; Jia, Wei

    2017-01-01

    Introduction Gut microbiota plays critical roles in drug metabolism. The individual variation of gut microbiota contributes to the interindividual differences towards drug therapy including drug-induced toxicity and efficacy. Accordingly, the investigation and elucidation of gut microbial impacts on drug metabolism and toxicity will not only facilitate the way of personalized medicine, but also improve the rational drug design. Areas covered This review provide an overview on the microbiota-host cometabolism on drug metabolism and summarize 30 clinical drugs which are co-metabolized by host and gut microbiota. Moreover, this review is specifically focused on elucidating the gut microbial modulation on some clinical drugs, in which the gut microbial influences on drug metabolism, drug-induced toxicity and efficacy are intensively discussed. Expert opinion The gut microbial contribution to drug metabolism and toxicity is increasingly recognized, but remains largely unexplored due to the extremely complex relationship between gut microbiota and host. The mechanistic elucidation of gut microbiota in drug metabolism is critical before any practical progress in drug design or personalized medicine could be made by modulating human gut microbiota, which is predominantly relied on the technical innovations such as metagenomics and metabolomics, as well as the integration of multi-disciplinary knowledge. PMID:26569070

  17. Effects of carbamazepine on plasma extravasation and bronchoconstriction induced by substance P, capsaicin, acetaldehyde and histamine in guinea-pig lower airways.

    PubMed

    Bianchi, M; Rossoni, G; Maggi, R; Panerai, A E; Berti, F

    1998-01-01

    We evaluated the in vivo effects of the pretreatment with carbamazepine (CBZ) at different doses (10, 20 and 40 mg/kg p.o.) on the Evans-blue extravasation and on bronchoconstriction induced by different substances in guinea-pig tracheal tissue. The drug dose-dependently inhibited the extravasation induced by substance P (SP), capsaicin and acetaldehyde, but not that induced by histamine. At the highest dose (40 mg/kg) CBZ inhibited the bronchoconstriction induced by SP, capsaicin and acetaldehyde, but not that produced by histamine administration. The in vitro study with guinea-pig tracheal preparation indicates that the drug does not interfere with the binding of SP to its receptors. Our results suggest that CBZ exerts a protective activity against the pro-inflammatory action of SP.

  18. Infrared spectra of complex organic molecules in astronomically relevant ice matrices. I. Acetaldehyde, ethanol, and dimethyl ether

    NASA Astrophysics Data System (ADS)

    Terwisscha van Scheltinga, J.; Ligterink, N. F. W.; Boogert, A. C. A.; van Dishoeck, E. F.; Linnartz, H.

    2018-03-01

    Context. The number of identified complex organic molecules (COMs) in inter- and circumstellar gas-phase environments is steadily increasing. Recent laboratory studies show that many such species form on icy dust grains. At present only smaller molecular species have been directly identified in space in the solid state. Accurate spectroscopic laboratory data of frozen COMs, embedded in ice matrices containing ingredients related to their formation scheme, are still largely lacking. Aim. This work provides infrared reference spectra of acetaldehyde (CH3CHO), ethanol (CH3CH2OH), and dimethyl ether (CH3OCH3) recorded in a variety of ice environments and for astronomically relevant temperatures, as needed to guide or interpret astronomical observations, specifically for upcoming James Webb Space Telescope observations. Methods: Fourier transform transmission spectroscopy (500-4000 cm-1/20-2.5 μm, 1.0 cm-1 resolution) was used to investigate solid acetaldehyde, ethanol and dimethyl ether, pure or mixed with water, CO, methanol, or CO:methanol. These species were deposited on a cryogenically cooled infrared transmissive window at 15 K. A heating ramp was applied, during which IR spectra were recorded until all ice constituents were thermally desorbed. Results: We present a large number of reference spectra that can be compared with astronomical data. Accurate band positions and band widths are provided for the studied ice mixtures and temperatures. Special efforts have been put into those bands of each molecule that are best suited for identification. For acetaldehyde the 7.427 and 5.803 μm bands are recommended, for ethanol the 11.36 and 7.240 μm bands are good candidates, and for dimethyl ether bands at 9.141 and 8.011 μm can be used. All spectra are publicly available in the Leiden Database for Ice.

  19. Carbonyls in the metropolitan area of Mexico City: calculation of the total photolytic rate constants Kp(s(-1)) and photolytic lifetime (tau) of ambient formaldehyde and acetaldehyde.

    PubMed

    Báez, Armando P; Torres, Ma del Carmen B; García, Rocío M; Padilla, Hugo G

    2002-01-01

    A great number of studies on the ambient levels of formaldehyde and other carbonyls in the urban rural and maritime atmospheres have been published because of their chemical and toxicological characteristics, and adverse health effects. Due to their toxicological effects, it was considered necessary to measure these compounds at different sites in the metropolitan area of Mexico City, and to calculate the total rate of photolytic constants and the photolytic lifetime of formaldehyde and acetaldehyde. Four sites were chosen. Sampling was carried out at different seasons and atmospheric conditions. The results indicated that formaldehyde was the most abundant carbonyl, followed by acetone and acetaldehyde. Data sets obtained from the 4 sites were chosen to calculate the total rate of photolysis and the photolytic lifetime for formaldehyde and acetaldehyde. Maximum photolytic rate values were obtained at the maximum actinic fluxes, as was to be expected.

  20. Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

    PubMed

    Kang, Gaeun; Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jin; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jong-Keun

    2014-06-01

    It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results

  1. Acetaldehyde Content and Oxidative Stress in the Deleterious Effects of Alcohol Drinking on Rat Uterine Horn

    PubMed Central

    Buthet, Lara Romina; Maciel, María Eugenia; Quintans, Leandro Néstor; Rodríguez de Castro, Carmen; Costantini, Martín Hernán; Castro, José Alberto

    2013-01-01

    After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t-butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol. PMID:24348548

  2. Metabolic differences in cattle with excitable temperaments can influence productivity

    USDA-ARS?s Scientific Manuscript database

    Temperament can negatively affect various production traits, including live weight, ADG, DMI, conception rates, and carcass weight. Three research studies are summarized which indicate the potential influence of temperament on metabolism. In Brahman heifers, (n=12) the 6 most temperamental and 6 mos...

  3. The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells.

    PubMed Central

    Page, R A; Kitson, K E; Hardman, M J

    1991-01-01

    We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps. PMID:1898355

  4. Pharmacokinetics of ethanol and its metabolite, acetaldehyde, and fetolethality in the third-trimester pregnant guinea pig for oral administration of acute, multiple-dose ethanol.

    PubMed

    Clarke, D W; Steenaart, N A; Slack, C J; Brien, J F

    1986-08-01

    The pharmacokinetics of ethanol and its metabolite, acetaldehyde, were determined in the third-trimester pregnant guinea pig (56-59 days gestation) for oral intubation of four doses of 1 g ethanol/kg maternal body weight, administered at 1-h intervals. Animals (n = 4-7) were sacrificed at each of selected times during the 26-h study. Ethanol and acetaldehyde concentrations were determined by headspace gas-liquid chromatography. The maternal and fetal blood ethanol concentration-time curves were virtually superimposable, which indicated unimpeded bidirectional placental transfer of ethanol in the maternal-fetal unit. The blood and brain ethanol concentrations were similar in each of the maternal and fetal compartments during the study, which indicated rapid equilibrium distribution of ethanol. There was accumulation of ethanol in the amniotic fluid resulting in higher ethanol concentration compared with maternal and fetal blood during the elimination phase, which indicated that the amniotic fluid may serve as a reservoir for ethanol in utero. Acetaldehyde was measurable in all the biological fluids and tissues at concentrations that were at least 1,000-fold less than the respective ethanol concentrations and were variable. There was ethanol-induced fetolethality that was delayed and variable among animals, and was 55% at 23 h. At this time interval, the ethanol concentrations in maternal blood and brain, fetal brain, and amniotic fluid were 35- to 53-fold greater and the acetaldehyde concentrations in maternal blood and fetal brain were four- to five-fold higher in the animals with dead fetuses compared with the guinea pigs with live litters. These data indicated that decreased ethanol elimination from the maternal-fetal unit was related temporally to the fetolethality.

  5. Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of Alcohol Dehydrogenase for Exhaled Acetaldehyde.

    PubMed

    Iitani, Kenta; Chien, Po-Jen; Suzuki, Takuma; Toma, Koji; Arakawa, Takahiro; Iwasaki, Yasuhiko; Mitsubayashi, Kohji

    2018-02-23

    Volatile organic compounds (VOCs) exhaled in breath have huge potential as indicators of diseases and metabolisms. Application of breath analysis for disease screening and metabolism assessment is expected since breath samples can be noninvasively collected and measured. In this research, a highly sensitive and selective biochemical gas sensor (bio-sniffer) for gaseous acetaldehyde (AcH) was developed. In the AcH bio-sniffer, a reverse reaction of alcohol dehydrogenase (ADH) was employed for reducing AcH to ethanol and simultaneously consuming a coenzyme, reduced form of nicotinamide adenine dinucleotide (NADH). The concentration of AcH can be quantified by fluorescence detection of NADH that was consumed by reverse reaction of ADH. The AcH bio-sniffer was composed of an ultraviolet light-emitting diode (UV-LED) as an excitation light source, a photomultiplier tube (PMT) as a fluorescence detector, and an optical fiber probe, and these three components were connected with a bifurcated optical fiber. A gas-sensing region of the fiber probe was developed with a flow-cell and an ADH-immobilized membrane. In the experiment, after optimization of the enzyme reaction conditions, the selectivity and dynamic range of the AcH bio-sniffer were investigated. The AcH bio-sniffer showed a short measurement time (within 2 min) and a broad dynamic range for determination of gaseous AcH, 0.02-10 ppm, which encompassed a typical AcH concentration in exhaled breath (1.2-6.0 ppm). Also, the AcH bio-sniffer exhibited a high selectivity to gaseous AcH based on the specificity of ADH. The sensor outputs were observed only from AcH-contained standard gaseous samples. Finally, the AcH bio-sniffer was applied to measure the concentration of AcH in exhaled breath from healthy subjects after ingestion of alcohol. As a result, a significant difference of AcH concentration between subjects with different aldehyde dehydrogenase type 2 (ALDH2) phenotypes was observed. The AcH bio-sniffer can be

  6. Theoretical survey of the reaction between osmium and acetaldehyde

    NASA Astrophysics Data System (ADS)

    Dai, Guo-Liang; Wang, Chuan-Feng

    2012-05-01

    The mechanism of the reaction of osmium atom with acetaldehyde has been investigated with a DFT approach. All the stationary points are determined at the UB3LYP/ sdd/6-311++G** level of the theory. Both ground and excited state potential energy surfaces are investigated in detail. The present results show that the title reaction start with the formation of a CH3CHO-metal complex followed by C-C, aldehyde C-H, C-O, and methyl C-H activation. These reactions can lead to four different products (HOsCH3 + CO, OsCO + CH4, OsCOCH3 + H, and OsO + C2H4). The minimum energy reaction path is found to involve the spin inversion in the initial reaction step. This potential energy curve-crossing dramatically affects reaction exothermic. The present results may be helpful in understanding the mechanism of the title reaction and further experimental investigation of the reaction.

  7. The ketogenic diet: metabolic influences on brain excitability and epilepsy

    PubMed Central

    Lutas, Andrew; Yellen, Gary

    2012-01-01

    A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use in the past decade. Though the diet’s underlying mechanism remains unknown, modern scientific approaches like genetic disruption of glucose metabolism are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy. PMID:23228828

  8. Microbial pathway for anaerobic 5′-methylthioadenosine metabolism coupled to ethylene formation

    PubMed Central

    North, Justin A.; Miller, Anthony R.; Wildenthal, John A.; Young, Sarah J.; Tabita, F. Robert

    2017-01-01

    Numerous cellular processes involving S-adenosyl-l-methionine result in the formation of the toxic by-product, 5′-methylthioadenosine (MTA). To prevent inhibitory MTA accumulation and retain biologically available sulfur, most organisms possess the “universal” methionine salvage pathway (MSP). However, the universal MSP is inherently aerobic due to a requirement of molecular oxygen for one of the key enzymes. Here, we report the presence of an exclusively anaerobic MSP that couples MTA metabolism to ethylene formation in the phototrophic bacteria Rhodospirillum rubrum and Rhodopseudomonas palustris. In vivo metabolite analysis of gene deletion strains demonstrated that this anaerobic MSP functions via sequential action of MTA phosphorylase (MtnP), 5-(methylthio)ribose-1-phosphate isomerase (MtnA), and an annotated class II aldolase-like protein (Ald2) to form 2-(methylthio)acetaldehyde as an intermediate. 2-(Methylthio)acetaldehyde is reduced to 2-(methylthio)ethanol, which is further metabolized as a usable organic sulfur source, generating stoichiometric amounts of ethylene in the process. Ethylene induction experiments using 2-(methylthio)ethanol versus sulfate as sulfur sources further indicate anaerobic ethylene production from 2-(methylthio)ethanol requires protein synthesis and that this process is regulated. Finally, phylogenetic analysis reveals that the genes corresponding to these enzymes, and presumably the pathway, are widespread among anaerobic and facultatively anaerobic bacteria from soil and freshwater environments. These results not only establish the existence of a functional, exclusively anaerobic MSP, but they also suggest a possible route by which ethylene is produced by microbes in anoxic environments. PMID:29133429

  9. Inhibition of human alcohol and aldehyde dehydrogenases by cimetidine and assessment of its effects on ethanol metabolism.

    PubMed

    Lai, Ching-Long; Li, Yeung-Pin; Liu, Chiu-Ming; Hsieh, Hsiu-Shan; Yin, Shih-Jiun

    2013-02-25

    Previous studies have reported that cimetidine, an H2-receptor antagonist used to treat gastric and duodenal ulcers, can inhibit alcohol dehydrogenases (ADHs) and ethanol metabolism. Human alcohol dehydrogenases and aldehyde dehydrogenases (ALDHs), the principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition by cimetidine of alcohol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and aldehyde oxidation by ALDH1A1 and ALDH2 at pH 7.5 and a cytosolic NAD(+) concentration. Cimetidine acted as competitive or noncompetitive inhibitors for the ADH and ALDH isozymes/allozymes with near mM inhibition constants. The metabolic interactions between cimetidine and ethanol/acetaldehyde were assessed by computer simulation using the inhibition equations and the determined kinetic constants. At therapeutic drug levels (0.015 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μM) in target tissues, cimetidine could weakly inhibit (<5%) the activities of ADH1B2 and ADH1B3 in liver, ADH2 in liver and small intestine, ADH4 in stomach, and ALDH1A1 in the three tissues, but not significantly affect ADH1A, ADH1B1, ADH1C1/2, or ALDH2. At higher drug levels, which may accumulate in cells (0.2 mM), the activities of the weakly-inhibited enzymes may be decreased more significantly. The quantitative effects of cimetidine on metabolism of ethanol and other physiological substrates of ADHs need further investigation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Thz Spectroscopy of Acetaldehyde and Search of 13C Species in Orion

    NASA Astrophysics Data System (ADS)

    Margulès, L.; Motiyenko, R. A.; Ilyushin, V. V.; Tercero, B.; Cernicharo, J.; Guillemin, J.-C.

    2012-06-01

    Acetaldehyde (CH_3CHO) is one of the high priority complex organic molecules for the astrophysical community. There is a lack of data concerning the 13C species since the measurements are limited to 40 GHz up to date. This molecule displays a large amplitude motion: the hindered rotation of the methyl group with respect to the rest of the molecule. The analysis is performed with RAM36 code which used the Rho Axis Method. Last year we presented the analysis of the millimeterwave spectra of the 13CH_3CHO species. We extended the analysis to the THz range of the vibrational ground state for both species. We are also analyzing the first torsional state (≈140 cm-1) for two reasons: first, this permits to remove correlation between parameters. Second, this state contribute to the partition function even at ISM temperature (100--150 K) since there is an influence on the column density determined in case of detection. The searches of these isotopomers are in progress in ORION. This work was supported by the CNES and the Action sur Projets de l'INSU, PCMI. This work was also done under the ANR-08-BLAN-0054. Kilb, R.W.; Lin, C.C.; and Wilson, E.B. J. Chem. Phys. 26, (1957) 1695 Ilyushin, V.V. et al J. Mol. Spectrosc. 259, (2010) 26 Margules, L. et al. FA07, 66th International Symposium on Molecular Spectroscopy (2011)

  11. Metabolic Surgery Profoundly Influences Gut Microbial-Host Metabolic Crosstalk

    PubMed Central

    Li, Jia V.; Ashrafian, Hutan; Bueter, Marco; Kinross, James; Sands, Caroline; le Roux, Carel W; Bloom, Stephen R.; Darzi, Ara; Athanasiou, Thanos; Marchesi, Julian R.; Nicholson, Jeremy K.; Holmes, Elaine

    2013-01-01

    Background and Aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes. Methods We apply a parallel and statistically integrated metagenomic and metabonomic approach to characterize Roux-en-Y gastric bypass (RYGB) effects in a rat model. Results We show substantial shifts of the main gut phyla towards higher levels of Proteobacteria (52-fold) specifically Enterobacter hormaechei. We also find low levels of Firmicutes (4.5-fold) and Bacteroidetes (2-fold) in comparison to sham-operated rats. Faecal extraction studies reveal a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diamnoethane. We find decreased urinary amines and cresols and demonstrate indices of modulated energy metabolism post-RYGB including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which associates with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically-induced effect on the gut-brain-liver metabolic axis is inferred by increased neurotropic compounds; faecal γ-aminobutyric acid (GABA) and glutamate. Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered following RYGB surgery, suggests that RYGB exerts local and global metabolic activities. The effect of RYGB surgery on the host metabolic-microbial crosstalk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases. PMID:21572120

  12. X and Y Chromosome Complement Influence Adiposity and Metabolism in Mice

    PubMed Central

    Chen, Xuqi; McClusky, Rebecca; Itoh, Yuichiro; Reue, Karen

    2013-01-01

    Three different models of MF1 strain mice were studied to measure the effects of gonadal secretions and sex chromosome type and number on body weight and composition, and on related metabolic variables such as glucose homeostasis, feeding, and activity. The 3 genetic models varied sex chromosome complement in different ways, as follows: 1) “four core genotypes” mice, comprising XX and XY gonadal males, and XX and XY gonadal females; 2) the XY* model comprising groups similar to XO, XX, XY, and XXY; and 3) a novel model comprising 6 groups having XO, XX, and XY chromosomes with either testes or ovaries. In gonadally intact mice, gonadal males were heavier than gonadal females, but sex chromosome complement also influenced weight. The male/female difference was abolished by adult gonadectomy, after which mice with 2 sex chromosomes (XX or XY) had greater body weight and percentage of body fat than mice with 1 X chromosome. A second sex chromosome of either type, X or Y, had similar effects, indicating that the 2 sex chromosomes each possess factors that influence body weight and composition in the MF1 genetic background. Sex chromosome complement also influenced metabolic variables such as food intake and glucose tolerance. The results reveal a role for the Y chromosome in metabolism independent of testes and gonadal hormones and point to a small number of X–Y gene pairs with similar coding sequences as candidates for causing these effects. PMID:23397033

  13. Diet-gene interactions underlie metabolic individuality and influence brain development: implications for clinical practice derived from studies on choline metabolism.

    PubMed

    Zeisel, Steven H

    2012-01-01

    One of the underlying mechanisms for metabolic individuality is genetic variation. Single nucleotide polymorphisms (SNPs) in genes of metabolic pathways can create metabolic inefficiencies that alter the dietary requirement for, and responses to, nutrients. These SNPs can be detected using genetic profiling and the metabolic inefficiencies they cause can be detected using metabolomic profiling. Studies on the human dietary requirement for choline illustrate how useful these new approaches can be, as this requirement is influenced by SNPs in genes of choline and folate metabolism. In adults, these SNPs determine whether people develop fatty liver, liver damage and muscle damage when eating diets low in choline. Because choline is very important for fetal development, these SNPs may identify women who need to eat more choline during pregnancy. Some of the actions of choline are mediated by epigenetic mechanisms that permit 'retuning' of metabolic pathways during early life. Copyright © 2012 S. Karger AG, Basel.

  14. Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.

    PubMed

    Karlsson, L; Zackrisson, A-L; Josefsson, M; Carlsson, B; Green, H; Kugelberg, F C

    2015-04-01

    We investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes influence the metabolic ratios and enantiomeric S/R ratios of venlafaxine (VEN) and its metabolites O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in blood from forensic autopsy cases. In all, 94 postmortem cases found positive for VEN during toxicological screening were included. The CYP2D6 genotype was shown to significantly influence the ODV/VEN (P=0.003), DDV/NDV (P=0.010) and DDV/ODV (P=0.034) ratios. The DDV/ODV (P=0.013) and DDV/VEN (P=0.021) ratios were significantly influenced by the CYP2C19 genotype. The S/R ratios of VEN were significantly influenced by both CYP2D6 and CYP2C19 genotypes. CYP2D6 poor metabolizers (PMs) had lower S/R VEN ratios and CYP2C19 PMs had high S/R ratios of VEN in comparison. Our results show that the CYP2D6 genotype influences the O-demethylation whereas CYP2C19 influences the N-demethylation of VEN and its metabolites. In addition, we show a stereoselective metabolism where CYP2D6 favours the R-enantiomer whereas CYP2C19 favours the S-enantiomer.

  15. The Molecular and Metabolic Influence of Long Term Agmatine Consumption*

    PubMed Central

    Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne L.; Nissim, Ilana; Yudkoff, Marc

    2014-01-01

    Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used 13C or 15N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming. PMID:24523404

  16. Efficient adsorption concentration and photolysis of acetaldehyde on titania-mesoporous silica composite

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Satoshi; Matsumoto, Akihiko

    2017-07-01

    Titania-mesoporous silica composite (TiO2/MCM) was prepared by hydrolysis of titaniumtetraisopropoxide (TTIP) with the presence of mesoporous silica MCM-41. The TiO2/MCM samples consisted of highly dispersed TiO2 on the surface of MCM-41. Dynamic adsorption and photocatalytic decomposition features for acetaldehyde (CH3CHO) were measured by flow method. The amount of CH3CHO decomposition on TiO2/MCM-41 increased with the TiO2 amount, suggesting that a large amount of CH3CHO was adsorbed on mesopores of MCM-41 of the TiO2/MCM and was efficiently decomposed on finely dispersed TiO2 surface by ultraviolet irradiation.

  17. Fetal metabolic influences of neonatal anthropometry and adiposity.

    PubMed

    Donnelly, Jean M; Lindsay, Karen L; Walsh, Jennifer M; Horan, Mary; Molloy, Eleanor J; McAuliffe, Fionnuala M

    2015-11-10

    Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring. Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity. Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant. Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

  18. Influence of Threonine Metabolism on S-adenosyl-methionine and Histone Methylation

    PubMed Central

    Shyh-Chang, Ng; Locasale, Jason W.; Lyssiotis, Costas A.; Zheng, Yuxiang; Teo, Ren Yi; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Asara, John M.; Daley, George Q.; Cantley, Lewis C.

    2013-01-01

    Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs) but the detailed mechanism remains unclear. We found that threonine (Thr) and S-adenosyl-methionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that Thr provides a substantial fraction of both the cellular glycine (Gly) and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of Thr from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased tri-methylation of histone H3 lysine-4 (H3K4me3), leading to slowed growth, and increased differentiation. Thus abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate. PMID:23118012

  19. Sensitive gas chromatographic detection of acetaldehyde and acetone using a reduction gas detector

    NASA Technical Reports Server (NTRS)

    O'Hara, Dean; Singh, Hanwant B.

    1988-01-01

    The response of a newly available mercuric oxide Reduction Gas Detector (RGD-2) to subpicomole and larger quantities of acetaldehyde and acetone is tested. The RGD-2 is found to be capable of subpicomole detection for these carbonyls and is more sensitive than an FID (Flame Ionization Detector) by an order of magnitude. Operating parameters can be further optimized to make the RGD-2 some 20-40 times more sensitive than an FID. The detector is linear over a wide range and is easily adapted to a conventional gas chromatograph (GC). Such a GC-RGD-2 system should be suitable for atmospheric carbonyl measurements in clean as well as polluted environments.

  20. Concerns regarding 24-h sampling for formaldehyde, acetaldehyde, and acrolein using 2,4-dinitrophenylhydrazine (DNPH)-coated solid sorbents

    NASA Astrophysics Data System (ADS)

    Herrington, Jason S.; Hays, Michael D.

    2012-08-01

    There is high demand for accurate and reliable airborne carbonyl measurement methods due to the human and environmental health impacts of carbonyls and their effects on atmospheric chemistry. Standardized 2,4-dinitrophenylhydrazine (DNPH)-based sampling methods are frequently applied for measuring gaseous carbonyls in the atmospheric environment. However, there are multiple short-comings associated with these methods that detract from an accurate understanding of carbonyl-related exposure, health effects, and atmospheric chemistry. The purpose of this brief technical communication is to highlight these method challenges and their influence on national ambient monitoring networks, and to provide a logical path forward for accurate carbonyl measurement. This manuscript focuses on three specific carbonyl compounds of high toxicological interest—formaldehyde, acetaldehyde, and acrolein. Further method testing and development, the revision of standardized methods, and the plausibility of introducing novel technology for these carbonyls are considered elements of the path forward. The consolidation of this information is important because it seems clear that carbonyl data produced utilizing DNPH-based methods are being reported without acknowledgment of the method short-comings or how to best address them.

  1. Metabolic and hormone influences on emotion processing during menopause.

    PubMed

    Berent-Spillson, Alison; Marsh, Courtney; Persad, Carol; Randolph, John; Zubieta, Jon-Kar; Smith, Yolanda

    2017-02-01

    Disturbances of emotion regulation and depressive symptoms are common during the menopause transition. Reproductive hormone levels are not directly correlated with depressive symptoms, and other factors may influence mood symptoms during menopause. In this study, we sought to determine the role of metabolic function in mood symptoms during menopause, hypothesizing an association with menopause status and long-term glucose load. We studied 54 women across three menopause transition stages (15 premenopause, 11 perimenopause, and 28 postmenopause), examining effects of age, hormones, and metabolism on mood and neural activation during emotional discrimination. We assessed participants using behavioral and functional MRI measures of negative emotion and emotion discrimination, and glycated hemoglobin A1c, to assess long-term glucose load. We found that emotionally unpleasant images activated emotion regulation (amygdala) and cognitive association brain regions (prefrontal cortex, posterior cingulate, temporal-parietal-occipital (TPO) junction, hippocampus). Cognitive association region activity increased with menopause stage. Perimenopausal women had left TPO junction activation, and postmenopausal women had prefrontal cortex, posterior cingulate, and TPO junction activation. Negative affect was associated with decreased amygdala activation, while depression symptoms and negative mood were associated with increased TPO junction activation. Hemoglobin A1c was associated with negative interpretation bias of neutral images and cognitive region recruitment during emotion discrimination. FSH levels, indicating menopause stage, were associated with negative mood. Age was not associated with any behavioral measures or activation patterns during the emotion task. Our results suggest that an interaction between metabolic and hormonal factors may influence emotion regulation, leading to increased risk for depression during menopause. Copyright © 2016 Elsevier Ltd. All rights

  2. Effects of Beverages on Alcohol Metabolism: Potential Health Benefits and Harmful Impacts

    PubMed Central

    Wang, Fang; Zhang, Yu-Jie; Zhou, Yue; Li, Ya; Zhou, Tong; Zheng, Jie; Zhang, Jiao-Jiao; Li, Sha; Xu, Dong-Ping; Li, Hua-Bin

    2016-01-01

    Nonalcoholic beverages are usually consumed accompanying alcoholic drinks, and their effects on alcohol metabolism are unclear in vivo. In this study, the effects of 20 nonalcoholic beverages on alcohol metabolism and liver injury caused by alcohol were evaluated in mice. Kunming mice were orally fed with alcohol (52%, v/v) and beverages. The concentrations of ethanol and acetaldehyde in blood as well as the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver were assessed to indicate alcohol metabolism. The levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) in serum as well as the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) in liver were measured to reflect the alcohol-induced liver injury. The results showed that the treatment of soda water, green tea and honey chrysanthemum tea could accelerate ethanol metabolism and prevent liver injuries caused by alcohol when companied with excessive alcohol drinking. They might be potential dietary supplements for the alleviation of harmful effects from excessive alcohol consumption. On the contrary, some beverages such as fresh orange juice and red bull are not advised to drink when companied with alcohol consumption due to their adverse effects on ethanol induced liver injury. PMID:27005619

  3. [Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol].

    PubMed

    Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

    2012-08-01

    From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.

  4. Visible-Light Upconversion Carbon Quantum Dots Decorated TiO2 for the Photodegradation of Flowing Gaseous Acetaldehyde

    NASA Astrophysics Data System (ADS)

    Hu, Yidan; Xie, Xiaofeng; Wang, Xiao; Wang, Yan; Zeng, Yi; Pui, David Y. H.; Sun, Jing

    2018-05-01

    Carbon-modified photocatalyst has attracted extensive attentions in the field of gaseous pollutant removal, mainly due to the improved adsorption properties and electronic transport of carbon matrix, such as carbon nanotubes, graphene, and fullerene, etc. In this work, carbon quantum dots (CQDs) were employed to enhance the photocatalytic performance of TiO2-based composites for flowing gaseous acetaldehyde removal. Besides the aforementioned advantages of carbon materials, the unique up-converted photoluminescence property of CQDs is capable of extending the optical absorption to visible-light range. Moreover, the electron spin resonance (ESR) results firstly verified a stable existence of Ti3+ defect in the CQDs/TiO2 composite, which is possibly induced by the electron migration from CQDs to TiO2. And the formed Ti3+ donor energy level in the band gap could further help with the visible-light harvesting. During the photodegradation experiments, with two-hour continuous flowing gaseous acetaldehyde injection (500 ppm, 20 sccm), the CQDs/TiO2 composite remained 99% removal efficiency under fluorescent lamp irradiation (λ > 380 nm). The optimized CQDs content was obtained as 3 wt%, and the underlying mechanism was further analyzed by temperature programmed desorption (TPD) methods. This work will push forward the air purification researches by providing new insights of CQDs sensitized photocatalyst.

  5. Influence of temperature, oxygen and salinity on the metabolism of the European sea bass

    NASA Astrophysics Data System (ADS)

    Claireaux, G.; Lagardère, J.-P.

    1999-09-01

    Standard (SMR) and routine (RMR) metabolic rates of groups (4 to 5 individuals) of European sea bass ( Dicentrarchus labrax) were measured at combinations of the following factors: temperature (10, 15, 20 and 25°C), oxygenation level (air saturation to 1.5 mg dm -3) and salinity (30, 20, 10 and 5‰). The influence of these environmental conditions on fish metabolic demand was then analysed through ANOVA. At 10, 15, 20 and 25°C, standard metabolic rates were 36, 65, 89, and 91 mg O 2 kg -1 h -1, respectively, while routine oxygen consumptions covered most of the metabolic range accessible. Osmoregulatory costs are linked to metabolic activity through ventilation. This relationship was highlighted by the observed interaction between environmental salinity and temperature. We were, however, unable to detect interactions between salinity and routine metabolic rate, or between salinity and oxygenation level. In order to delineate more precisely the restrictions imposed by water oxygenation on fish metabolic performance we determined the limiting oxygen concentration curves at each experimental temperature. We followed up by modelling the bass active metabolic rate (AMR) and metabolic scope (MS) as functions of both ambient temperature and oxygenation. These mathematical models allowed the characterisation of the controlling and limiting effects of water temperature and oxygen content on the metabolic capacity of the species. Thus, AMR at 10, 15 and 20°C were estimated at 65, 160 and 360 mg O 2 kg -1 h -1, respectively. However, at higher temperature (25°C) AMR dropped slightly (to 340 mg O 2 kg -1 h -1). Bass MS increased by a factor of 9 between 10 and 20°C, but diminished at higher temperatures. The present study contributes to our current understanding of the influences of environmental factors on the metabolism of sea bass and provides a bioenergetic basis for a study of how environmental constraints govern the spatial and temporal distribution pattern of this

  6. Glucokinase regulatory proten genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome

    USDA-ARS?s Scientific Manuscript database

    Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3...

  7. A "Dual-acceptor Channel" Membraneless Gas-diffusion Unit for Simultaneous Determination of Ethanol and Acetaldehyde in Liquors Using Reverse Flow Injection.

    PubMed

    Choengchan, Nathawut; Poontong, Bangerdsuk; Mathaweesansurn, Arjnarong; Maneerat, Noppadol; Motomizu, Shoji; Ratanawimarnwong, Nuanlaor; Nacapricha, Duangjai

    2018-01-01

    A new design of membraneless gas-diffusion unit with dual acceptor channels for separation, collection and simultaneous determination of two volatile analytes in liquid sample is presented. The unit is comprised of three parallel channels in a closed module. A sample is aspirated into the central channel and two kinds of reagents are introduced into the other two channels. Two analytes are isolated from the sample matrix by diffusion into head-space and absorbed into the specific reagents. Non-absorbed vapor is released by opening the programmable controlled lid. The unit was applied to liquors for measurement of ethanol and acetaldehyde using reverse flow injection. Dichromate and nitroprusside were exploited as reagents for colorimetric detection of ethanol and acetaldehyde, respectively. Good linearity ranges (r 2 >0.99) with high precision (RSD <2%) and high accuracy (recovery: 90 - 105%) were achieved. The results were compared to the results by GC-FID and no significant difference was observed by paired t-test (95% confidence).

  8. Metabolic depression in cunner (Tautogolabrus adspersus) is influenced by ontogeny, and enhances thermal tolerance.

    PubMed

    Kelly, Nick I; Alzaid, Abdullah; Nash, Gordon W; Gamperl, A Kurt

    2014-01-01

    To examine the effect of ontogeny on metabolic depression in the cunner (Tautogolabrus adspersus), and to understand how ontogeny and the ability to metabolically depress influence this species' upper thermal tolerance: 1) the metabolic rate of 9°C-acclimated cunner of three size classes [0.2-0.5 g, young of the year (YOY); 3-6 g, small; and 80-120 g, large (adult)] was measured during a 2°C per day decrease in temperature; and 2) the metabolic response of the same three size classes of cunner to an acute thermal challenge [2°C h(-1) from 10°C until Critical Thermal Maximum, CTMax] was examined, and compared to that of the Atlantic cod (Gadus morhua). The onset-temperature for metabolic depression in cunner increased with body size, i.e. from 5°C in YOY cunner to 7°C in adults. In contrast, the extent of metabolic depression was ∼80% (Q10 = ∼15) for YOY fish, ∼65% (Q10 = ∼8) for small fish and ∼55% (Q10 = ∼5) for adults, and this resulted in the metabolic scaling exponent (b) gradually increasing from 0.84 to 0.92 between 9°C to 1°C. All size classes of cunner had significantly (approximately 60%) lower routine metabolic rates at 10°C than Atlantic cod. However, there was no species' difference in the temperature-induced maximum metabolic rate, and this resulted in factorial metabolic scope values that were more than two-fold greater for cunner, and CTMax values that were 6-9°C higher (∼21 vs. 28°C). These results: 1) show that ontogeny influences the temperature of initiation and the extent of metabolic depression in cunner, but not O2 consumption when in a hypometabolic state; and 2) suggest that the evolution of cold-induced metabolic depression in this northern wrasse species has not resulted in a trade-off with upper thermal tolerance, but instead, an enhancement of this species' metabolic plasticity.

  9. Metabolic Depression in Cunner (Tautogolabrus adspersus) Is Influenced by Ontogeny, and Enhances Thermal Tolerance

    PubMed Central

    Nash, Gordon W.; Gamperl, A. Kurt

    2014-01-01

    To examine the effect of ontogeny on metabolic depression in the cunner (Tautogolabrus adspersus), and to understand how ontogeny and the ability to metabolically depress influence this species' upper thermal tolerance: 1) the metabolic rate of 9°C-acclimated cunner of three size classes [0.2–0.5 g, young of the year (YOY); 3–6 g, small; and 80–120 g, large (adult)] was measured during a 2°C per day decrease in temperature; and 2) the metabolic response of the same three size classes of cunner to an acute thermal challenge [2°C h−1 from 10°C until Critical Thermal Maximum, CTMax] was examined, and compared to that of the Atlantic cod (Gadus morhua). The onset-temperature for metabolic depression in cunner increased with body size, i.e. from 5°C in YOY cunner to 7°C in adults. In contrast, the extent of metabolic depression was ∼80% (Q10 = ∼15) for YOY fish, ∼65% (Q10 = ∼8) for small fish and ∼55% (Q10 = ∼5) for adults, and this resulted in the metabolic scaling exponent (b) gradually increasing from 0.84 to 0.92 between 9°C to 1°C. All size classes of cunner had significantly (approximately 60%) lower routine metabolic rates at 10°C than Atlantic cod. However, there was no species' difference in the temperature-induced maximum metabolic rate, and this resulted in factorial metabolic scope values that were more than two-fold greater for cunner, and CTMax values that were 6–9°C higher (∼21 vs. 28°C). These results: 1) show that ontogeny influences the temperature of initiation and the extent of metabolic depression in cunner, but not O2 consumption when in a hypometabolic state; and 2) suggest that the evolution of cold-induced metabolic depression in this northern wrasse species has not resulted in a trade-off with upper thermal tolerance, but instead, an enhancement of this species' metabolic plasticity. PMID:25514755

  10. Isotopic separation of acetaldehyde and methanol from their deuterated isotopologues on a porous layer open tubular column allows quantification by stable isotope dilution without mass spectrometric detection.

    PubMed

    Schmarr, Hans-Georg; Wacker, Michael; Mathes, Maximilian

    2017-01-20

    An isotopic separation of acetaldehyde and acetaldehyde-2,2,2-d3 was achieved in a temperature programmed run on a porous layer open tubular (PLOT) capillary column coated with particles of divinylbenzene ethylene glycol/dimethylacrylate (Rt ® -U-BOND). This is the prerequisite for the development of quantitative analytical methods based on a stable isotope dilution assay (SIDA) without a mass spectrometric detection (non-MS SIDA). For routine analysis a flame ionization detector (FID) can thus be applied as a robust and low-cost alternative. In a preliminary study, static headspace extraction and gas chromatographic separation (HS-GC-FID) of acetaldehyde in aqueous solutions was shown as an application. Good linearity was obtained in a calibration range from 0.4 to 40mgL -1 , with peak integration benefitting from the inverse isotope effect encountered on the specific porous polymer. Furthermore, separation of methanol and deuterated methanol (d3) could also be achieved under the same chromatographic conditions. The achieved isotopic separation of these important volatile compounds now allows non-MS SIDA-based methods that are still to be developed. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements.

    PubMed

    Ganz, Ariel B; Klatt, Kevin C; Caudill, Marie A

    2017-08-04

    Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches.

  12. Common Genetic Variants Alter Metabolism and Influence Dietary Choline Requirements

    PubMed Central

    Ganz, Ariel B.; Klatt, Kevin C.; Caudill, Marie A.

    2017-01-01

    Nutrient needs, including those of the essential nutrient choline, are a population wide distribution. Adequate Intake (AI) recommendations for dietary choline (put forth by the National Academies of Medicine to aid individuals and groups in dietary assessment and planning) are grouped to account for the recognized unique needs associated with age, biological sex, and reproductive status (i.e., pregnancy or lactation). Established and emerging evidence supports the notion that common genetic variants are additional factors that substantially influence nutrient requirements. This review summarizes the genetic factors that influence choline requirements and metabolism in conditions of nutrient deprivation, as well as conditions of nutrient adequacy, across biological sexes and reproductive states. Overall, consistent and strong associative evidence demonstrates that common genetic variants in choline and folate pathway enzymes impact the metabolic handling of choline and the risk of nutrient inadequacy across varied dietary contexts. The studies characterized in this review also highlight the substantial promise of incorporating common genetic variants into choline intake recommendations to more precisely target the unique nutrient needs of these subgroups within the broader population. Additional studies are warranted to facilitate the translation of this evidence to nutrigenetics-based dietary approaches. PMID:28777294

  13. Influence of dietary macronutrients on liver fat accumulation and metabolism

    PubMed Central

    Parry, Siôn A; Hodson, Leanne

    2017-01-01

    The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated. PMID:28947639

  14. Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells.

    PubMed

    Berger, John P; Simet, Samantha M; DeVasure, Jane M; Boten, Jessica A; Sweeter, Jenea M; Kharbanda, Kusum K; Sisson, Joseph H; Wyatt, Todd A

    2014-08-01

    Co-exposure to cigarette smoke and ethanol generates malondialdehyde and acetaldehyde, which can subsequently lead to the formation of aldehyde-adducted proteins. We have previously shown that exposure of bronchial epithelial cells to malondialdehyde-acetaldehyde (MAA) adducted protein increases protein kinase C (PKC) activity and proinflammatory cytokine release. A specific ligand to scavenger receptor A (SRA), fucoidan, blocks this effect. We hypothesized that MAA-adducted protein binds to bronchial epithelial cells via SRA. Human bronchial epithelial cells (BEAS-2B) were exposed to MAA-adducted protein (either bovine serum albumin [BSA-MAA] or surfactant protein D [SPD-MAA]) and SRA examined using confocal microscopy, fluorescent activated cell sorting (FACS), and immunoprecipitation. Differentiated mouse tracheal epithelial cells (MTEC) cultured by air-liquid interface were assayed for MAA-stimulated PKC activity and keratinocyte-derived chemokine (KC) release. Specific cell surface membrane dye co-localized with upregulated SRA after exposure to MAA for 3-7 min and subsided by 20 min. Likewise, MAA-adducted protein co-localized to SRA from 3 to 7 min with a subsequent internalization of MAA by 10 min. These results were confirmed using FACS analysis and revealed a reduced mean fluorescence of SRA after 3 min. Furthermore, increased amounts of MAA-adducted protein could be detected by Western blot in immunoprecipitated SRA samples after 3 min treatment with MAA. MAA stimulated PKCε-mediated KC release in wild type, but not SRA knockout mice. These data demonstrate that aldehyde-adducted proteins in the lungs rapidly bind to SRA and internalize this receptor prior to the MAA-adducted protein stimulation of PKC-dependent inflammatory cytokine release in airway epithelium. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Malondialdehyde-acetaldehyde (MAA) adducted proteins bind to scavenger receptor A in airway epithelial cells

    PubMed Central

    Berger, John P.; Simet, Samantha M.; DeVasure, Jane M.; Boten, Jessica A.; Sweeter, Jenea M.; Kharbanda, Kusum K.; Sisson, Joseph H.; Wyatt, Todd A.

    2014-01-01

    Co-exposure to cigarette smoke and ethanol generates malondialdehyde and acetaldehyde, which can subsequently lead to the formation of aldehyde-adducted proteins. We have previously shown that exposure of bronchial epithelial cells to malondialdehyde-acetaldehyde (MAA) adducted protein increases protein kinase C (PKC) activity and proinflammatory cytokine release. A specific ligand to scavenger receptor A (SRA), fucoidan, blocks this effect. We hypothesized that MAA-adducted protein binds to bronchial epithelial cells via SRA. Human bronchial epithelial cells (BEAS-2B) were exposed to MAA-adducted protein (either bovine serum albumin [BSA-MAA] or surfactant protein D [SPD-MAA]) and SRA examined using confocal microscopy, fluorescent activated cell sorting (FACS), and immunoprecipitation. Differentiated mouse tracheal epithelial cells (MTEC) cultured by air-liquid interface were assayed for MAA-stimulated PKC activity and keratinocyte-derived chemokine (KC) release. Specific cell surface membrane dye co-localized with upregulated SRA after exposure to MAA for 3–7 min and subsided by 20 min. Likewise, MAA-adducted protein co-localized to SRA from 3–7 min with a subsequent internalization of MAA by 10 min. These results were confirmed using FACS analysis and revealed a reduced mean fluorescence of SRA after 3 min. Furthermore, increased amounts of MAA-adducted protein could be detected by Western blot in immunoprecipitated SRA samples after 3 min treatment with MAA. MAA stimulated PKCε-mediated KC release in wild type, but not SRA knockout mice. These data demonstrate that aldehyde-adducted proteins in the lungs rapidly bind to SRA and internalize this receptor prior to the MAA-adducted protein stimulation of PKC-dependent inflammatory cytokine release in airway epithelium. PMID:24880893

  16. Diet-gene interactions underlie metabolic individuality and influence brain development: Implications for clinical practice

    PubMed Central

    Zeisel, Steven H.

    2014-01-01

    One of the underlying mechanisms for metabolic individuality is genetic variation. Single nucleotide polymorphisms (SNPs) in genes of metabolic pathways can create metabolic inefficiencies that alter the dietary requirement for, and responses to nutrients. These SNPS can be detected using genetic profiling and the metabolic inefficiencies they cause can be detected using metabolomic profiling. Studies on the human dietary requirement for choline illustrate how useful these new approaches can be, as this requirement is influenced by SNPs in genes of choline and folate metabolism. In adults, these SNPs determine whether people develop fatty liver, liver damage and muscle damage when eating diets low in choline. Because choline is very important for fetal development, these SNPs may identify women who need to eat more choline during pregnancy. Some of the actions of choline are mediated by epigenetic mechanisms that permit “retuning” of metabolic pathways during early life. PMID:22614815

  17. Validation and Determination of the Contents of Acetaldehyde and Formaldehyde in Foods

    PubMed Central

    Jeong, Hye-Seung; Chung, Hyun; Song, Sang-Hoon; Kim, Cho-Il; Lee, Joon-Goo

    2015-01-01

    The aim of this study was to develop an efficient quantitative method for the determination of acetaldehyde (AA) and formaldehyde (FA) contents in solid and liquid food matrices. The determination of those compounds was validated and performed using gas chromatography-mass spectrometry combined by solid phase micro-extraction after derivatization with O-(2,3,4,5,6-pentafluoro-benzyl)-hydroxylamine hydrochloride. Validation was carried out in terms of limit of detection, limit of quantitation, linearity, precision, and recovery. Then their contents were analyzed in various food samples including 15 fruits, 22 milk products, 31 alcohol-free beverages, and 13 alcoholic beverages. The highest contents of AA and FA were determined in a white wine (40,607.02 ng/g) and an instant coffee (1,522.46 ng/g), respectively. PMID:26483886

  18. A Kinetic Modelling of Enzyme Inhibitions in the Central Metabolism of Yeast Cells

    NASA Astrophysics Data System (ADS)

    Kasbawati; Kalondeng, A.; Aris, N.; Erawaty, N.; Azis, M. I.

    2018-03-01

    Metabolic regulation plays an important role in the metabolic engineering of a cellular process. It is conducted to improve the productivity of a microbial process by identifying the important regulatory nodes of a metabolic pathway such as fermentation pathway. Regulation of enzymes involved in a particular pathway can be held to improve the productivity of the system. In the central metabolism of yeast cell, some enzymes are known as regulating enzymes that can be inhibited to increase the production of ethanol. In this research we study the kinetic modelling of the enzymes in the central pathway of yeast metabolism by taking into consideration the enzyme inhibition effects to the ethanol production. The existence of positive steady state solution and the stability of the system are also analysed to study the property and dynamical behaviour of the system. One stable steady state of the system is produced if some conditions are fulfilled. The conditions concern to the restriction of the maximum reactions of the enzymes in the pyruvate and acetaldehyde branch points. There exists a certain time of fermentation reaction at which a maximum and a minimum ethanol productions are attained after regulating the system. Optimal ethanol concentration is also produced for a certain initial concentration of inhibitor.

  19. Is hepatic lipid metabolism of beef cattle influenced by breed and dietary silage level?

    PubMed Central

    2014-01-01

    Background In ruminants, unsaturated dietary fatty acids are biohydrogenated in the rumen and are further metabolised in various tissues, including liver, which has an important role in lipid and lipoprotein metabolism. Therefore, manipulation of muscle fatty acid composition should take into account liver metabolism. In the present study, the influence of breed and diet on liver lipid composition and gene expression was investigated in order to clarify the role of this organ in the lipid metabolism of ruminants. Forty purebred young bulls from two phylogenetically distant autochthonous cattle breeds, Alentejana and Barrosã, were assigned to two different diets (low vs. high silage) and slaughtered at 18 months of age. Liver fatty acid composition, mRNA levels of enzymes and transcription factors involved in lipid metabolism, as well as the plasma lipid profile, were assessed. Results In spite of similar plasma non-esterified fatty acids levels, liver triacylglycerols content was higher in Barrosã than in Alentejana bulls. Moreover, the fatty acid composition of liver was clearly distinct from the remaining tissues involved in fatty acid metabolism of ruminants, as shown by Principal Components Analysis. The hepatic tissue is particularly rich in α-linolenic acid and their products of desaturation and elongation. Results indicate that DGAT1, ELOVL2, FADS1 and FADS2 genes influence the fatty acid composition of the liver the most. Moreover, genes such as DGAT1 and ELOVL2 appear to be more sensitive to genetic background than to dietary manipulation, whereas genes encoding for desaturases, such as FADS1, appear to be modulated by dietary silage level. Conclusions Our results indicate that liver plays an important role in the biosynthesis of n-3 LC-PUFA. It is also suggested that dietary silage level influences the hepatic fatty acid metabolism in a breed-dependent manner, through changes in the expression of genes encoding for enzymes associated with the

  20. Hypothesis of demodicidosis rosacea flushing etiopathogenesis.

    PubMed

    Robledo, Mary Ann; Orduz, Mariana

    2015-04-01

    Most of the patients with erythematotelangiectatic rosacea are characterized by flushing, oedema and telangiectasia. The etiopathogenesis of the flushing in rosacea patients is unknown. Clinically the flushing in rosacea is similar to the "Asian flushing syndrome". Most Asians have an overactive alcohol dehydrogenase (ADH) that tends to break down alcohol into acetaldehyde faster. People with "Asians flushing syndrome" have a genetic disorder with the Aldehyde Dehydrogenase 2(∗)2 (ALDH2(∗)2) allele. This is the reason why they do not metabolize very well the acetaldehyde that comes from the alcohol, which means that acetaldehyde takes much longer to clear from their blood. ALDH2 enzyme is primarily responsible for oxidation of acetaldehyde derived from ethanol metabolism, as well as oxidation of various other endogenous and exogenous aldehydes. Acetaldehyde produces the vasodilatation in the "Asian flushing syndrome". The antibodies against the GroEl chaperonin protein, a 62-kDa heat shock protein were found in the Bacillus oleronius isolated from Demodex mites, in rosacea patients. The GroEl chaperonin protein is a protein that plays a key role in normal folding of ALDH2. If the GroEl chaperonin antibodies found in patients with rosacea, cross react with the human GroEl chaperonin protein, they will not fold normally the ALDH2, and then the enzyme will not metabolize the acetaldehyde. Many of the patients with rosacea have a concomitant infection with Helicobacter pylori in their stomach. The H.pylori produces high amounts of acetaldehyde, which comes from their metabolism of ethanol or carbohydrates. As a result, high amounts of acetaldehyde will circulate for longer time in the blood, until the liver CYP2E1(p450) enzyme system finally metabilizes the acetaldehyde, during that period of time the patients will experience a flushing as well as the people with the "Asian flushing syndrome" suffer when they drink ethanol. To prove the hypothesis it is necessary

  1. Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: Assessment of the effects on first-pass metabolism of ethanol.

    PubMed

    Lee, Yung-Pin; Liao, Jian-Tong; Cheng, Ya-Wen; Wu, Ting-Lun; Lee, Shou-Lun; Liu, Jong-Kang; Yin, Shih-Jiun

    2013-11-01

    Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mM NAD(+). Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (Kis) ranging from 0.90 mM (ADH2) to 20 mM (ADH1A), and the intercept inhibition constants (Kii) ranging from 1.4 mM (ADH1C allozymes) to 19 mM (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (Kis = 3.0 mM and Kii = 2.2 mM), but competitive inhibition for ALDH1A1 (Kis = 0.96 mM). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2-0.5 mM) and physiologically relevant concentrations of ethanol (10 mM) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12-26%) and ADH2 (14-28%) in the liver and small intestine, ADH4 (15-31%) in the stomach, and ALDH1A1 (16-33%) and ALDH2 (8.3-19%) in all 3 tissues. The

  2. Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

    PubMed

    Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

    2016-04-01

    To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

  3. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

    PubMed

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-04-07

    Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

  4. Trypsin-catalyzed tandem reaction: one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones by in situ formed acetaldehyde.

    PubMed

    Xie, Zong-Bo; Wang, Na; Wu, Wan-Xia; Le, Zhang-Gao; Yu, Xiao-Qi

    2014-01-20

    A simple, mild, one-pot tandem method catalyzed by trypsin was developed for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by the Biginelli reaction of urea, β-dicarbonyl compounds, and in situ-formed acetaldehyde. Trypsin was found to display dual promiscuous functions to catalyze transesterification and the Biginelli reaction in sequence. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents.

    PubMed

    Acevedo, María B; D'Aloisio, Génesis; Haymal, Olga B; Molina, Juan C

    2017-01-01

    Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the

  6. Role of Alcohol Metabolism in Chronic Pancreatitis

    PubMed Central

    Vonlaufen, Alain; Wilson, Jeremy S.; Pirola, Romano C.; Apte, Minoti V.

    2007-01-01

    Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis of alcoholic pancreatitis was related to ductular and sphincteric abnormalities. In recent years, the focus has shifted to the type of pancreas cell that produces digestive juices (i.e., acinar cell). Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and nonoxidative pathways. The isolation and study of pancreatic stellate cells (PSCs)—the key effectors in the development of connective tissue fibers (i.e., fibrogenesis) in the pancreas—has greatly enhanced our understanding of the pathogenesis of chronic pancreatitis. Pancreatic stellate cells become activated in response to ethanol and acetaldehyde, a toxic byproduct of alcohol metabolism. In addition, PSCs have the capacity to metabolize alcohol via alcohol dehydrogenase (the major oxidizing enzyme for ethanol). The fact that only a small percentage of heavy alcoholics develop chronic pancreatitis has led to the search for precipitating factors of the disease. Several studies have investigated whether variations in ethanol-metabolizing enzymes may be a trigger factor for chronic pancreatitis, but no definite relationship has been established so far. PMID:17718401

  7. Aging rather than stress strongly influences amino acid metabolisms in the brain and genital organs of female mice.

    PubMed

    Kodaira, Momoko; Nagasawa, Mao; Yamaguchi, Takeshi; Ikeda, Hiromi; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2017-03-01

    Aging and stress affect quality of life, and proper nourishment is one of means of preventing this effect. Today, there is a focus on the amount of protein consumed by elderly people; however, changes in the amino acid metabolism of individuals have not been fully considered. In addition, the difference between average life span and healthy life years is larger in females than it is in males. To prolong the healthy life years of females, in the present study we evaluated the influence of stress and aging on metabolism and emotional behavior by comparing young and middle-aged female mice. After 28 consecutive days of immobilization stress, behavioral tests were conducted and tissue sampling was performed. The results showed that the body weight of middle-aged mice was severely lowered by stress, but emotional behaviors were hardly influenced by either aging or stress. Aging influenced changes in amino acid metabolism in the brain and increased various amino acid levels in the uterus and ovary. In conclusion, we found that aged mice were more susceptible to stress in terms of body-weight reduction, and that amino acid metabolisms in the brain and genital organs were largely influenced by aging rather than by stress. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Influence of dietary macronutrients on liver fat accumulation and metabolism.

    PubMed

    Parry, Siôn A; Hodson, Leanne

    2017-12-01

    The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Investigation of carbohydrate and protein metabolism in the digestive organs of the rabbit under the combined influence of vibration, acceleration and irradiation

    NASA Technical Reports Server (NTRS)

    Yuy, R. I.

    1975-01-01

    During spaceflight, the organism is subjected to the influence of various extremal factors such as acceleration, vibration, irradiation, etc. The study of the influence of these factors on metabolism, especially carbohydrate and protein metabolism, in young rabbits is of great significance in simulation experiments. Dynamic factors and irradiation, depending on dose and duration, lead to reduced RNA and protein metabolism.

  10. Growth and Metabolism of Lactic Acid Bacteria during and after Malolactic Fermentation of Wines at Different pH

    PubMed Central

    Davis, C. R.; Wibowo, D. J.; Lee, T. H.; Fleet, G. H.

    1986-01-01

    Commercially produced red wines were adjusted to pH 3.0, 3.2, 3.5, 3.7, or 4.0 and examined during and after malolactic fermentation for growth of lactic acid bacteria and changes in the concentrations of carbohydrates, organic acids, amino acids, and acetaldehyde. With one exception, Leuconostoc oenos conducted the malolactic fermentation in all wines and was the only species to occur in wines at pH below 3.5. Malolactic fermentation by L. oenos was accompanied by degradation of malic, citric, and fumaric acids and production of lactic and acetic acids. The concentrations of arginine, histidine, and acetaldehyde also decreased at this stage, but the behavior of hexose and pentose sugars was complicated by other factors. Pediococcus parvulus conducted the malolactic fermentation in one wine containing 72 mg of total sulfur dioxide per liter. Fumaric and citric acids were not degraded during this malolactic fermentation, but hexose sugars were metabolized. P. parvulus and species of Lactobacillus grew after malolactic fermentation in wines with pH adjusted above 3.5. This growth was accompanied by the utilization of wine sugars and production of lactic and acetic acids. PMID:16347015

  11. Influence of metal concentrations, percent salinity, and length of exposure on the metabolic rate of fathead minnows (Pimephales promelas).

    PubMed

    Pistole, David H; Peles, John D; Taylor, Kelly

    2008-07-01

    Understanding the effects of chemical toxicants on energetic processes is an important aspect of ecotoxicology. However, the influence of toxicant concentration and time of exposure on metabolism in aquatic organisms is still poorly understood. The purpose of this investigation was to determine the influence of increasing levels of three stressors (Cu, Cd, percent salinity) and exposure time (24 h and 96 h) on the metabolic rate of fathead minnows (Pimephales promelas). In all 24-h exposures, there existed a threshold concentration, above which metabolic rate decreased significantly compared to the control and lower concentrations. In contrast, the metabolic rate of fish exposed for 96 h increased significantly in all concentrations compared to fish from the control. We suggest fathead minnows exhibit a consistent pattern of metabolic response to stressors, regardless of the physiological mechanisms involved, and that this response differs as a function of time of exposure.

  12. Inhibition of 1,4-butanediol metabolism in human liver in vitro.

    PubMed

    Lenz, Daniel; Jübner, Martin; Bender, Katja; Wintermeyer, Annette; Beike, Justus; Rothschild, Markus A; Käferstein, Herbert

    2011-06-01

    The conversion of 1,4-butanediol (1,4-BD) to gamma-hydroxybutyric acid (GHB), a drug of abuse, is most probably catalyzed by alcohol dehydrogenase, and potentially by aldehyde dehydrogenase. The purpose of this study was to investigate the degradation of 1,4-BD in cytosolic supernatant of human liver in vitro, and to verify involvement of the suggested enzymes by means of gas chromatography-mass spectrometry. The coingestion of 1,4-BD and ethanol (EtOH) might cause complex pharmacokinetic interactions in humans. Therefore, the effect of EtOH on 1,4-BD metabolism by human liver was examined in vitro. Additionally, the influence of acetaldehyde (AL), which might inhibit the second step of 1,4-BD degradation, was investigated. In case of a 1,4-BD intoxication, the alcohol dehydrogenase inhibitor fomepizole (4-methylpyrazole, FOM) has been discussed as an antidote preventing the formation of the central nervous system depressing GHB. Besides FOM, we tested pyrazole, disulfiram, and cimetidine as possible inhibitors of the formation of GHB from 1,4-BD catalyzed by human liver enzymes in vitro. The conversion of 1,4-BD to GHB was inhibited competitively by EtOH with an apparent K(i) of 0.56 mM. Therefore, the coingestion of 1,4-BD and EtOH might increase the concentrations and the effects of 1,4-BD itself. By contrast AL accelerated the formation of GHB. All antidotes showed the ability to inhibit the formation of GHB. In comparison FOM showed the highest inhibitory effectiveness. Furthermore, the results confirm strong involvement of ADH in 1,4-BD metabolism by human liver.

  13. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    PubMed

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  14. Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

    PubMed Central

    Thompson, Jacqueline R.; Gustafsson, Hanna C.; DeCapo, Madison; Takahashi, Diana L.; Bagley, Jennifer L.; Dean, Tyler A.; Kievit, Paul; Fair, Damien A.; Sullivan, Elinor L.

    2018-01-01

    Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation. PMID:29740395

  15. Acetaldehyde Stimulates FANCD2 Monoubiquitination, H2AX Phosphorylation, and BRCA1 Phosphorylation in Human Cells in Vitro: Implications for Alcohol-Related Carcinogenesis

    PubMed Central

    Marietta, Cheryl; Thompson, Larry H.; Lamerdin, Jane E.; Brooks, P.J.

    2009-01-01

    According to a recent IARC Working Group report, alcohol consumption is causally related to an increased risk of cancer of the upper aerodigestive tract, liver, colorectum, and female breast (Lancet Oncol. 2007 8:292–3). Several lines of evidence indicate that acetaldehyde (AA), the first product of alcohol metabolism, plays a very important role in alcohol-related carcinogenesis, particularly in the esophagus. We previously proposed a model for alcohol-related carcinogenesis in which AA, generated from alcohol metabolism, reacts in cells to generate DNA lesions that form interstrand crosslinks (ICLs) (Nucleic Acids Res. 2005 33:3513–20). Since the Fanconi anemia-breast cancer associated (FANC-BRCA) DNA damage response network plays a crucial role in protecting cells against ICLs, in the present work we tested this hypothesis by exposing cells to AA and monitoring activation of this network. We found that AA exposure results in a concentration-dependent increase in FANCD2 monoubiquitination, which is dependent upon the FANC core complex. AA also stimulated BRCA1 phosphorylation at Ser1524 and increased the level of γH2AX, with both modifications occurring in a dose-dependent manner. However, AA did not detectably increase the levels of hyperphosphorylated RPA34, a marker of single-stranded DNA exposure at replication forks. These results provide the initial description of the AA-DNA damage response, which is qualitatively similar to the cellular response to mitomycin C, a known DNA crosslinking agent. We discuss the mechanistic implications of these results, as well as their possible relationship to alcohol-related carcinogenesis in different human tissues. PMID:19428384

  16. Metabolic profiling of apples from different production systems before and after controlled atmosphere (CA) storage studied by 1H high resolution-magic angle spinning (HR-MAS) NMR.

    PubMed

    Vermathen, Martina; Marzorati, Mattia; Diserens, Gaëlle; Baumgartner, Daniel; Good, Claudia; Gasser, Franz; Vermathen, Peter

    2017-10-15

    Determination of metabolic alterations in apples induced by such processes as different crop protection strategies or storage, are of interest to assess correlations with fruit quality or fruit disorders. Preliminary results proposed the metabolic discrimination of apples from organic (BIO), integrated (IP) and low-input (LI) production. To determine contributions of temporal metabolic developments and to define the type of metabolic changes during storage, 1 H high resolution-magic angle spinning (HR-MAS) NMR spectroscopy of apple pulp was performed before and after two time points of controlled atmosphere storage. Statistical analysis revealed similar metabolic changes over time for IP-, LI- and BIO-samples, mainly decreasing lipid and sucrose, and increasing fructose, glucose and acetaldehyde levels, which are potential contributors to fruit aroma. Across the production systems, BIO apples had consistently higher levels of fructose and monomeric phenolic compounds but lower levels of condensed polyphenols than LI and IP apples, while the remaining metabolites assimilated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Metabolic influences on neuroendocrine regulation of reproduction.

    PubMed

    Navarro, Víctor M; Kaiser, Ursula B

    2013-08-01

    Reproduction is a tightly regulated function in which many mechanisms contribute to ensure the survival of the species. Among those, due to the elevated energy requirements of reproduction, metabolic factors exert a pivotal role in the control of hypothalamic-pituitary-gonadal axis. Although this control may occur at multiple levels of the axis, the majority of interactions between metabolic and reproductive systems take place in the hypothalamus. In this article, we present an overview of the state-of-the-art knowledge regarding the metabolic regulation of reproduction at the central level. We aim to identify the neuroanatomical location where both functions interconnect by discussing the likelihood of each component of the neuronal hierarchical network controlling gonadotropin-releasing hormone (GnRH) release to be first-order responders to metabolic cues, especially the peripheral metabolic signals leptin, insulin, and ghrelin. Latest evidence suggests that the primary action of leptin, insulin, and ghrelin to regulate reproduction is located upstream of the main central elicitors of gonadotropin release, Kiss1 and GnRH neurons, and neuroanatomically separated from their metabolic action. The study of the neuronal interactions between the mechanisms governing metabolism and reproduction offers the platform to overcome or treat a number of prevailing metabolic and/or reproductive conditions.

  18. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    PubMed

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

  19. Contribution of ALDH2 polymorphism to alcoholism-associated hypertension.

    PubMed

    Hu, Nan; Zhang, Yingmei; Nair, Sreejayan; Culver, Bruce W; Ren, Jun

    2014-01-01

    Chronic alcohol intake is considered as an independent lifestyle factor that may influence the risk of a number of cardiovascular anomalies including hypertension. In healthy adults, binge drinking and chronic alcohol ingestion lead to the onset and development of hypertension although the precise mechanism(s) remains obscure. Although oxidative stress and endothelial injury have been postulated to play a major contributing role to alcoholism-induced hypertension, recent evidence depicted a rather unique role for the genotype of the acetaldehyde-metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), which is mainly responsible for detoxifying ethanol consumed, in alcoholism-induced elevation of blood pressure. Genetic polymorphism of ALDH2 in human results in altered ethanol pharmacokinetic properties and ethanol metabolism, leading to accumulation of the ethanol metabolite acetaldehyde following alcohol intake. The unfavorable consequence of the ALDH2 variants is believed to be governed by the accumulation of the ethanol metabolite acetaldehyde. Presence of the mutant or inactive ALDH2*2 gene often results in an increased risk of hypertension in human. Such association between blood pressure and ALDH2 enzymatic activity may be affected by the interplay between gene and environment, such as life style and ethnicity. The aim of this mini-review is to summarize the possible contribution of ALDH2 genetic polymorphism in the onset and development of alcoholism-related development of hypertension. Furthermore, the double-edged sword of ALDH2 gene and genetic polymorphism in alcoholism and alcoholic tissue damage and relevant patents will be discussed.

  20. Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase.

    PubMed Central

    Burdette, D; Zeikus, J G

    1994-01-01

    The purification and characterization of three enzymes involved in ethanol formation from acetyl-CoA in Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E) is described. The secondary-alcohol dehydrogenase (2 degrees Adh) was determined to be a homotetramer of 40 kDa subunits (SDS/PAGE) with a molecular mass of 160 kDa. The 2 degrees Adh had a lower catalytic efficiency for the oxidation of 1 degree alcohols, including ethanol, than for the oxidation of secondary (2 degrees) alcohols or the reduction of ketones or aldehydes. This enzyme possesses a significant acetyl-CoA reductive thioesterase activity as determined by NADPH oxidation, thiol formation and ethanol production. The primary-alcohol dehydrogenase (1 degree Adh) was determined to be a homotetramer of 41.5 kDa (SDS/PAGE) subunits with a molecular mass of 170 kDa. The 1 degree Adh used both NAD(H) and NADP(H) and displayed higher catalytic efficiencies for NADP(+)-dependent ethanol oxidation and NADH-dependent acetaldehyde (identical to ethanal) reduction than for NADPH-dependent acetaldehyde reduction or NAD(+)-dependent ethanol oxidation. The NAD(H)-linked acetaldehyde dehydrogenase was a homotetramer (360 kDa) of identical subunits (100 kDa) that readily catalysed thioester cleavage and condensation. The 1 degree Adh was expressed at 5-20% of the level of the 2 degrees Adh throughout the growth cycle on glucose. The results suggest that the 2 degrees Adh primarily functions in ethanol production from acetyl-CoA and acetaldehyde, whereas the 1 degree Adh functions in ethanol consumption for nicotinamide-cofactor recycling. Images Figure 1 PMID:8068002

  1. The Influence of Metabolic Syndrome and Sex on the DNA Methylome in Schizophrenia

    PubMed Central

    Lines, Brittany N.

    2018-01-01

    Introduction The mechanism by which metabolic syndrome occurs in schizophrenia is not completely known; however, previous work suggests that changes in DNA methylation may be involved which is further influenced by sex. Within this study, the DNA methylome was profiled to identify altered methylation associated with metabolic syndrome in a schizophrenia population on atypical antipsychotics. Methods Peripheral blood from schizophrenia subjects was utilized for DNA methylation analyses. Discovery analyses (n = 96) were performed using an epigenome-wide analysis on the Illumina HumanMethylation450K BeadChip based on metabolic syndrome diagnosis. A secondary discovery analysis was conducted based on sex. The top hits from the discovery analyses were assessed in an additional validation set (n = 166) using site-specific methylation pyrosequencing. Results A significant increase in CDH22 gene methylation in subjects with metabolic syndrome was identified in the overall sample. Additionally, differential methylation was found within the MAP3K13 gene in females and the CCDC8 gene within males. Significant differences in methylation were again observed for the CDH22 and MAP3K13 genes, but not CCDC8, in the validation sample set. Conclusions This study provides preliminary evidence that DNA methylation may be associated with metabolic syndrome and sex in schizophrenia. PMID:29850476

  2. Brain Acetaldehyde Exposure Impacts upon Neonatal Respiratory Plasticity and Ethanol-Related Learning in Rodents

    PubMed Central

    Acevedo, María B.; D'Aloisio, Génesis; Haymal, Olga B.; Molina, Juan C.

    2017-01-01

    Prior studies indicate that neonates are very sensitive to ethanol's positive reinforcing effects and to its depressant effects upon breathing. Acetaldehyde (ACD) appears to play a major role in terms of modulating early reinforcing effects of the drug. Yet, there is no pre-existing literature relative to the incidence of this metabolite upon respiratory plasticity. The present study analyzed physiological and behavioral effects of early central administrations of ethanol, acetaldehyde or vehicle. Respiration rates (breaths/min) were registered at post-natal days (PDs) 2 and 4 (post-administration time: 5, 60, or 120 min). At PD5, all pups were placed in a context (plethysmograph) where they had previously experienced the effects of central administrations and breathing patterns were recorded. Following this test, pups were evaluated using and operant conditioning procedure where ethanol or saccharin served as positive reinforcers. Body temperatures were also registered prior to drug administrations as well as at the beginning and the end of each specific evaluation. Across days, breathing responses were high at the beginning of the evaluation session and progressively declined as a function of the passage of time. At PDs 2 and 4, shortly after central administration (5 min), ACD exerted a significant depression upon respiration frequencies. At PD5, non-intoxicated pups with a prior history of ACD central administrations, exhibited a marked increase in respiratory frequencies; a result that probably indicates a conditioned compensatory response. When operant testing procedures were conducted, prior ethanol or ACD central administrations were found to reduce the reinforcing effects of ethanol. This was not the case when saccharin was employed as a reinforcer. As a whole, the results indicate a significant role of central ACD upon respiratory plasticity of the neonate and upon ethanol's reinforcing effects; phenomena that affect the physiological integrity of the

  3. Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.

    PubMed

    Saxena, Roheeni; Bozack, Anne K; Gamble, Mary V

    2018-05-23

    Exposure to inorganic arsenic (InAs) via drinking water and/or food is a considerable worldwide problem. Methylation of InAs generates monomethyl (MMAs III+V )- and dimethyl (DMAs III+V )-arsenical species in a process that facilitates urinary As elimination; however, MMA is considerably more toxic than either InAs or DMAs. Emerging evidence suggests that incomplete methylation of As to DMAs, resulting in increased MMAs, is associated with increased risk for a host of As-related health outcomes. The biochemical pathway that provides methyl groups for As methylation, one-carbon metabolism (OCM), is influenced by folate and other micronutrients, including choline and betaine. Individuals and species differ widely in their ability to methylate As. A growing body of research, including cell-culture, animal-model, and epidemiological studies, has demonstrated the role of OCM-related micronutrients in As methylation. This review examines the evidence that nutritional status and nutritional interventions can influence the metabolism and toxicity of As, with a primary focus on folate. Expected final online publication date for the Annual Review of Nutrition Volume 38 is August 21, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  4. Ethanol metabolism by alcohol dehydrogenase or cytochrome P450 2E1 differentially impairs hepatic protein trafficking and growth hormone signaling.

    PubMed

    Doody, Erin E; Groebner, Jennifer L; Walker, Jetta R; Frizol, Brittnee M; Tuma, Dean J; Fernandez, David J; Tuma, Pamela L

    2017-12-01

    The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P 450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol-fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion, and nuclear translocation and that the defects are likely mediated by acetaldehyde. However, the roles of CYP2E1-generated metabolites and ROS in microtubule acetylation and these alcohol-induced impairments have not been examined. To determine if CYP2E1-mediated alcohol metabolism is required for enhanced acetylation and the trafficking defects, we coincubated cells with ethanol and diallyl sulfide (DAS; a CYP2E1 inhibitor) or N -acetyl cysteine (NAC; an antioxidant). Both agents failed to prevent microtubule hyperacetylation in ethanol-treated cells and also failed to prevent impaired secretion or clathrin-mediated endocytosis. Somewhat surprisingly, both DAS and NAC prevented impaired STAT5B nuclear translocation. Further examination of microtubule-independent steps of the pathway revealed that Jak2/STAT5B activation by growth hormone was prevented by DAS and NAC. These results were confirmed in ethanol-exposed HepG2 cells expressing only ADH or CYP2E1. Using quantitative RT-PCR, we further determined that ethanol exposure led to blunted growth hormone-mediated gene expression. In conclusion, we determined that alcohol-induced microtubule acetylation and associated defects in microtubule-dependent trafficking are mediated by ADH metabolism whereas impaired microtubule-independent Jak2/STAT5B activation is mediated by CYP2E1 activity. NEW & NOTEWORTHY Impaired growth hormone-mediated signaling is observed in ethanol

  5. A Theoretical Investigation of the Plausibility of Reactions Between Ammonia and Carbonyl Species (Formaldehyde, Acetaldehyde, and Acetone) in Interstellar Ice Analogs at Ultracold Temperatures

    NASA Technical Reports Server (NTRS)

    Chen, Lina; Woon, David E.

    2011-01-01

    We have reexamined the reaction between formaldehyde and ammonia, which was previously studied by us and other workers in modestly sized cluster calculations. Larger model systems with up to 12H2O were employed, and reactions of two more carbonyl species, acetaldehyde and acetone, were also carried out. Calculations were performed at the B3LYP/6-31+G** level with bulk solvent effects treated with a polarizable continuum model; limited MP2/6-31+G** calculations were also performed. We found that while the barrier for the concerted proton relay mechanism described in previous work remains modest, it is still prohibitively high for the reaction to occur under the ultracold conditions that prevail in dense interstellar clouds. However, a new pathway emerged in more realistic clusters that involves at least one barrierless step for two of the carbonyl species considered here: ammonia reacts with formaldehyde and acetaldehyde to form a partial charge transfer species in small clusters (4H2O) and a protonated hydroxyamino intermediate species in large clusters (9H2O, 12H2O); modest barriers that decrease sharply with cluster size are found for the analogous processes for the acetone-NH3 reaction. Furthermore, if a second ammonia replaces one of the water molecules in calculations in the 9H2O clusters, deprotonation can occur to yield the same neutral hydroxyamino species that is formed via the original concerted proton relay mechanism. In at least one position, deprotonation is barrierless when zero-point energy is included. In addition to describing the structures and energetics of the reactions between formaldehyde, acetaldehyde, and acetone with ammonia, we report spectroscopic predictions of the observable vibrational features that are expected to be present in ice mixtures of different composition.

  6. Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle.

    PubMed

    Kinsey, Stephen T; Locke, Bruce R; Dillaman, Richard M

    2011-01-15

    Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients. It is therefore not surprising that skeletal muscle fibers have long been the focus of reaction-diffusion analyses because they have high and variable rates of ATP turnover, long diffusion distances, and hindered metabolite diffusion due to an abundance of intracellular barriers. Examination of the diversity of skeletal muscle fiber designs found in animals provides insights into the role that diffusion plays in governing both rates of metabolic fluxes and cellular organization. Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction-diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function. Foremost among these is that metabolic processes in muscles do, in fact, appear to be largely reaction controlled and are not greatly limited by diffusion. However, the influence of diffusion is apparent in patterns of fiber growth and metabolic organization that appear to result from selective pressure to maintain reaction control of metabolism in muscle.

  7. Molecules in motion: influences of diffusion on metabolic structure and function in skeletal muscle

    PubMed Central

    Kinsey, Stephen T.; Locke, Bruce R.; Dillaman, Richard M.

    2011-01-01

    Metabolic processes are often represented as a group of metabolites that interact through enzymatic reactions, thus forming a network of linked biochemical pathways. Implicit in this view is that diffusion of metabolites to and from enzymes is very fast compared with reaction rates, and metabolic fluxes are therefore almost exclusively dictated by catalytic properties. However, diffusion may exert greater control over the rates of reactions through: (1) an increase in reaction rates; (2) an increase in diffusion distances; or (3) a decrease in the relevant diffusion coefficients. It is therefore not surprising that skeletal muscle fibers have long been the focus of reaction–diffusion analyses because they have high and variable rates of ATP turnover, long diffusion distances, and hindered metabolite diffusion due to an abundance of intracellular barriers. Examination of the diversity of skeletal muscle fiber designs found in animals provides insights into the role that diffusion plays in governing both rates of metabolic fluxes and cellular organization. Experimental measurements of metabolic fluxes, diffusion distances and diffusion coefficients, coupled with reaction–diffusion mathematical models in a range of muscle types has started to reveal some general principles guiding muscle structure and metabolic function. Foremost among these is that metabolic processes in muscles do, in fact, appear to be largely reaction controlled and are not greatly limited by diffusion. However, the influence of diffusion is apparent in patterns of fiber growth and metabolic organization that appear to result from selective pressure to maintain reaction control of metabolism in muscle. PMID:21177946

  8. Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line

    PubMed Central

    Israel, Yedy; Karahanian, Eduardo; Ezquer, Fernando; Morales, Paola; Ezquer, Marcelo; Rivera-Meza, Mario; Herrera-Marschitz, Mario; Quintanilla, María E.

    2017-01-01

    This review article addresses the biological factors that influence: (i) the acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake; and (iii) alcohol relapse-like drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%–95%) for rats to display ethanol’s reinforcing effects and to initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine forming salsolinol, a compound that is self-administered. In UChB rats, salsolinol: (a) generates marked sensitization to the motivational effects of ethanol; and (b) strongly promotes binge-like drinking. The specificity of salsolinol actions is shown by the finding that only the R-salsolinol enantiomer but not S-salsolinol accounted for the latter effects. Inhibition of brain acetaldehyde synthesis does not influence the maintenance of chronic ethanol intake. However, a prolonged ethanol withdrawal partly returns the requirement for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol relapse-like drinking. Chronic ethanol intake, involving the action of lipopolysaccharide diffusing from the gut, and likely oxygen radical generated upon catechol/salsolinol oxidation, leads to oxidative stress and neuro-inflammation, known to potentiate each other. Data show that the administration of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol maintenance by 60%–70%, without inhibiting its initial intake. Intra-cerebroventricular administration of mesenchymal stem cells (MSCs), known to release anti-inflammatory cytokines, to elevate superoxide dismutase levels and to reverse ethanol-induced hippocampal injury and cognitive deficits, also inhibited chronic ethanol maintenance; further, relapse-like ethanol drinking was inhibited up to 85% for 40 days following intracerebral stem cell

  9. Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice.

    PubMed

    Liu, Qian; Shao, Wentao; Zhang, Chunlan; Xu, Cheng; Wang, Qihan; Liu, Hui; Sun, Haidong; Jiang, Zhaoyan; Gu, Aihua

    2017-07-01

    Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

    PubMed

    Herbeth, Bernard; Samara, Anastasia; Ndiaye, Coumba; Marteau, Jean-Brice; Berrahmoune, Hind; Siest, Gérard; Visvikis-Siest, Sophie

    2010-06-03

    We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters "risk lipids" and "protective lipids". Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: "liver enzymes", "adiposity/blood pressure" and "inflammation". Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Dynamic Adaptation of Liver Mitochondria to Chronic Alcohol Feeding in Mice

    PubMed Central

    Han, Derick; Ybanez, Maria D.; Johnson, Heather S.; McDonald, Jeniece N.; Mesropyan, Lusine; Sancheti, Harsh; Martin, Gary; Martin, Alanna; Lim, Atalie M; Dara, Lily; Cadenas, Enrique; Tsukamoto, Hidekazu; Kaplowitz, Neil

    2012-01-01

    Liver mitochondria undergo dynamic alterations following chronic alcohol feeding to mice. Intragastric alcohol feeding to mice resulted in 1) increased state III respiration (109% compared with control) in isolated liver mitochondria, probably due to increased levels of complexes I, IV, and V being incorporated into the respiratory chain; 2) increased mitochondrial NAD+ and NADH levels (∼2-fold), with no change in the redox status; 3) alteration in mitochondrial morphology, with increased numbers of elongated mitochondria; and 4) enhanced mitochondrial biogenesis in the liver, which corresponded with an up-regulation of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α). Oral alcohol feeding to mice, which is associated with less liver injury and steatosis, slightly enhanced respiration in isolated liver mitochondria (30.8% compared with control), lower than the striking increase caused by intragastric alcohol feeding. Mitochondrial respiration increased with both oral and intragastric alcohol feeding despite extensive N-acetylation of mitochondrial proteins. The alcohol-induced mitochondrial alterations are probably an adaptive response to enhance alcohol metabolism in the liver. Isolated liver mitochondria from alcohol-treated mice had a greater rate of acetaldehyde metabolism and respiration when treated with acetaldehyde than control. Aldehyde dehydrogenase-2 levels were unaltered in response to alcohol, suggesting that the greater acetaldehyde metabolism by isolated mitochondria from alcohol-treated mice was due to increased mitochondrial respiration that regenerated NAD+, the rate-limiting substrate in alcohol/acetaldehyde metabolism. Overall, our work suggests that mitochondrial plasticity in the liver may be an important adaptive response to the metabolic stress caused by alcohol intake and could potentially play a role in many other vital functions performed by the liver. PMID:23086958

  12. Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention.

    PubMed

    Syrjänen, Kari; Salminen, Johanna; Aresvuo, Ulla; Hendolin, Panu; Paloheimo, Lea; Eklund, Carita; Salaspuro, Mikko; Suovaniemi, Osmo

    2016-05-01

    Harmans are condensation products of acetaldehyde and biogenic amines in saliva. Like other monoamine oxidase inhibitors, harmans help maintain behavioral sensitization to nicotine and mediate the addictive potential of cigarette smoke-derived acetaldehyde. The aim of this study was to test the hypothesis that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium™ lozenge; Biohit Oyj, Helsinki, Finland) blocks the formation of harmans and eliminates acetaldehyde-enhanced nicotine addiction in smokers. A double-blind, randomized, placebo-controlled trial comparing Acetium lozenges and placebo in smoking intervention was undertaken. A cohort of 423 cigarette smokers were randomly allocated to intervention (n=212) and placebo arms (n=211). Smoking-related data were recorded by questionnaires, together with nicotine dependence testing by Fagerström scale. The participants used a smoking diary to record the daily number of cigarettes, test lozenges and sensations of smoking. The data were analyzed separately for point prevalence of abstinence and prolonged abstinence endpoints. Altogether, 110 study participants completed the trial per protocol, 234 had minor violations, and the rest (n=79) were lost to follow-up. During the 6-month trial, 65 participants quit smoking; 38 (17.9%) in the intervention arm and 27 (12.8%) in the placebo arm [odds ratio (OR)=1.48; 95% confidence intervals (CI)=0.87-2.54; p=0.143]. Success in the per protocol group was better (42.9% vs. 31.1%, respectively; OR=1.65, 95% CI=0.75-3.62; p=0.205) than in the modified intention-to-treat group: 13.5% vs. 7.4% (p=0.128). If the efficacy of Acetium lozenge can be confirmed in an adequately powered study, this new approach would represent a major breakthrough in smoking quit intervention because slow-release L-cysteine is non-toxic with no side-effects or limitations of use. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All

  13. Preparation of ordered mesoporous Ag/WO3 and its highly efficient degradation of acetaldehyde under visible-light irradiation.

    PubMed

    Sun, Songmei; Wang, Wenzhong; Zeng, Shaozhong; Shang, Meng; Zhang, Ling

    2010-06-15

    A highly active photocatalyst, silver loaded mesoporous WO(3), was successfully synthesized by an ultrasound assisted insertion method. The photodegradation of a common air pollutant acetaldehyde was adopted to evaluate the photocatalytic performance of the as-prepared sample under visible-light irradiation. The photocatalytic activity was about three and six times higher than that of pure mesoporous WO(3) and nitrogen-doped TiO(2), respectively. The photocatalytic mechanism was investigated to understand the much enhanced photocatalytic activity, which was mainly attributed to the largely improved electron-hole separation in the Ag-WO(3) heterojunction. Copyright 2010 Elsevier B.V. All rights reserved.

  14. Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5'-phosphate metabolism.

    PubMed Central

    Vech, R L; Lumeng, L; Li, T K

    1975-01-01

    Individuals with chronic alcohol abuse frequently exhibit lowered plasma levels of pyridoxal 5'-phosphate, the coenzyme form of vitamin B6. Because the liver is the primary source of this coenzyme in plasma and also the principal organ that oxidizes ethanol, the effect of ethanol on hepatic pyridoxal phosphate metabolism was studied in the rat. The chronic feeding of ethanol (36 percent of the total dietary calories) for 6 wk significantly decreased the hepatic pyridoxal phosphate content both in animals given a sufficient amount of vitamin B6 in their diet and in those rendered vitamin B6 deficient. In isolated perfused livers, the addition of 18 mM ethanol lowered the pyridoxal phosphate content of livers from vitamin B6-sufficient animals and deceased the net synthesis of pyridoxal phosphate from pyridoxine by the livers of vitamin B6-deficient animals. Ethanol also diminished the rate of release of pyridoxal phosphate into the perfusate by the livers of vitamin B6-deficient rats. These effects of ethanol, in vitro, were abolished by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase. Thus the derangement of pyridoxal phosphate metabolism produced by ethanol is dependt upon its oxidation. These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate. Images PMID:1168205

  15. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions

    PubMed Central

    Agnihotri, Sameer; Zadeh, Gelareh

    2016-01-01

    A defining hallmark of glioblastoma is altered tumor metabolism. The metabolic shift towards aerobic glycolysis with reprogramming of mitochondrial oxidative phosphorylation, regardless of oxygen availability, is a phenomenon known as the Warburg effect. In addition to the Warburg effect, glioblastoma tumor cells also utilize the tricarboxylic acid cycle/oxidative phosphorylation in a different capacity than normal tissue. Altered metabolic enzymes and their metabolites are oncogenic and not simply a product of tumor proliferation. Here we highlight the advantages of why tumor cells, including glioblastoma cells, require metabolic reprogramming and how tumor metabolism can converge on tumor epigenetics and unanswered questions in the field. PMID:26180081

  16. Organ-specific analysis of the anaerobic primary metabolism in rice and wheat seedlings. I: Dark ethanol production is dominated by the shoots.

    PubMed

    Mustroph, Angelika; Boamfa, Elena I; Laarhoven, Lucas J J; Harren, Frans J M; Albrecht, Gerd; Grimm, Bernhard

    2006-12-01

    During anaerobiosis in darkness the main route for ATP production in plants is through glycolysis in combination with fermentation. We compared the organ-specific anaerobic fermentation of flooding-tolerant rice (Oryza sativa) and sensitive wheat (Triticum aestivum) seedlings. A sensitive laser-based photoacoustic trace gas detection system was used to monitor emission of ethanol and acetaldehyde by roots and shoots of intact seedlings. Dark-incubated rice seedlings released 3 times more acetaldehyde and 14 times more ethanol than wheat seedlings during anaerobiosis. Ninety percent of acetaldehyde originated from shoots of both species. In comparison to wheat shoots, the high ethanol production of rice shoots correlated with larger amounts of soluble carbohydrates, and higher activities of fermentative enzymes. After 24 h of anaerobiosis in darkness rice shoots still contained 30% of aerated ATP level, which enabled seedlings to survive this period. In contrast, ATP content declined almost to zero in wheat shoots and roots, which were irreversibly damaged after a 24-h anaerobic period. When plants were anaerobically and dark incubated for 4 h and subsequently transferred back to aeration, shoots showed a transient peak of acetaldehyde release indicating prompt re-oxidation of ethanol. Post-anoxic acetaldehyde production was lower in rice seedlings than in wheat. This observation accounts for a more effective acetaldehyde detoxification system in rice. Compared to wheat the greater tolerance of rice seedlings to transient anaerobic periods is explained by a faster fermentation rate of their shoots allowing a sufficient ATP production and an efficient suppression of toxic acetaldehyde formation in the early re-aeration period.

  17. Asian flushing: genetic and sociocultural factors of alcoholism among East asians.

    PubMed

    Lee, Haeok; Kim, Sun S; You, Kwang Soo; Park, Wanju; Yang, Jin Hyang; Kim, Minjin; Hayman, Laura L

    2014-01-01

    Alcohol use can lead to a cascade of problems such as increased chances of risky behavior and negative health consequences, including alcoholic liver disease and upper gastric and liver cancer. Ethanol is metabolized mainly by 2 major enzymes: alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Genetic variations of genes encoding the 2 enzymes are very common among East Asians but relatively rare for most other populations. Facial flushing and other physical discomforts after alcohol drinking triggered by accumulation of acetaldehyde through defective genes for ADH and ALDH have been reported. Approximately 40% of East Asians (Chinese, Japanese, and Korean) show facial flushing after drinking alcohol, known as "Asian flush," which is characterized by adverse reactions on alcohol drinking in individuals possessing the fasting metabolizing alleles for ADH, ADH1B*2, and ADH1C*1, and the null allele for ALDH and ALDH2*2. Alcoholism is determined not only by the genetic deficiency but also by behaviors that involve complex interactions between genetic and sociocultural factors. The purpose of this article was to provide nurses with the most current information about genetic and sociocultural influences on alcoholism and alcohol-related health problems specifically for East Asians and implications of this knowledge to nursing practice. The physiological phenomenon of genes and genetics in relation to alcohol metabolism in this special population is emphasized.

  18. A Hepatocyte-Mimicking Antidote for Alcohol Intoxication.

    PubMed

    Xu, Duo; Han, Hui; He, Yuxin; Lee, Harrison; Wu, Di; Liu, Fang; Liu, Xiangsheng; Liu, Yang; Lu, Yunfeng; Ji, Cheng

    2018-04-11

    Alcohol intoxication causes serious diseases, whereas current treatments are mostly supportive and unable to remove alcohol efficiently. Upon alcohol consumption, alcohol is sequentially oxidized to acetaldehyde and acetate by the endogenous alcohol dehydrogenase and aldehyde dehydrogenase, respectively. Inspired by the metabolism of alcohol, a hepatocyte-mimicking antidote for alcohol intoxication through the codelivery of the nanocapsules of alcohol oxidase (AOx), catalase (CAT), and aldehyde dehydrogenase (ALDH) to the liver, where AOx and CAT catalyze the oxidation of alcohol to acetaldehyde, while ALDH catalyzes the oxidation of acetaldehyde to acetate. Administered to alcohol-intoxicated mice, the antidote rapidly accumulates in the liver and enables a significant reduction of the blood alcohol concentration. Moreover, blood acetaldehyde concentration is maintained at an extremely low level, significantly contributing to liver protection. Such an antidote, which can eliminate alcohol and acetaldehyde simultaneously, holds great promise for the treatment of alcohol intoxication and poisoning and can provide therapeutic benefits. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Effect of (L)-cysteine on acetaldehyde self-administration.

    PubMed

    Peana, Alessandra T; Muggironi, Giulia; Fois, Giulia R; Zinellu, Manuel; Sirca, Donatella; Diana, Marco

    2012-08-01

    Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered. This study examined the effects of l-cysteine pre-treatment during the acquisition and maintenance phases of ACD (0.2%) self-administration as well as on the deprivation effect after ACD extinction and on a progressive ratio (PR) schedule of reinforcement. In a separate PR schedule of reinforcement, the effect of l-cysteine was assessed on the break-point produced by ethanol (10%). Furthermore, we tested the effect of l-cysteine on saccharin (0.2%) reinforcement. Wistar rats were trained to self-administer ACD by nose poking on a fixed ratio (FR1) schedule in 30-min daily sessions. Responses on an active nose-poke caused delivery of ACD solution, whereas responses on an inactive nose-poke had no consequences. l-cysteine reduced the acquisition (40 mg/kg), the maintenance and the deprivation effect (100 mg/kg) of ACD self-administration. Furthermore, at the same dose, l-cysteine (120 mg/kg) decreased both ACD and ethanol break point. In addition, l-cysteine was unable to suppress the different responses for saccharin, suggesting that its effect did not relate to an unspecific decrease in a general motivational state. Compared to saline, l-cysteine did not modify responses on inactive nose-pokes, suggesting an absence of a non-specific behavioural activation. Taken together, these results could support the hypotheses that ACD possesses reinforcing properties and l-cysteine reduces motivation to self-administer ACD. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Influence of coral and algal exudates on microbially mediated reef metabolism.

    PubMed

    Haas, Andreas F; Nelson, Craig E; Rohwer, Forest; Wegley-Kelly, Linda; Quistad, Steven D; Carlson, Craig A; Leichter, James J; Hatay, Mark; Smith, Jennifer E

    2013-01-01

    Benthic primary producers in tropical reef ecosystems can alter biogeochemical cycling and microbial processes in the surrounding seawater. In order to quantify these influences, we measured rates of photosynthesis, respiration, and dissolved organic carbon (DOC) exudate release by the dominant benthic primary producers (calcifying and non-calcifying macroalgae, turf-algae and corals) on reefs of Mo'orea French Polynesia. Subsequently, we examined planktonic and benthic microbial community response to these dissolved exudates by measuring bacterial growth rates and oxygen and DOC fluxes in dark and daylight incubation experiments. All benthic primary producers exuded significant quantities of DOC (roughly 10% of their daily fixed carbon) into the surrounding water over a diurnal cycle. The microbial community responses were dependent upon the source of the exudates and whether the inoculum of microbes included planktonic or planktonic plus benthic communities. The planktonic and benthic microbial communities in the unamended control treatments exhibited opposing influences on DO concentration where respiration dominated in treatments comprised solely of plankton and autotrophy dominated in treatments with benthic plus plankon microbial communities. Coral exudates (and associated inorganic nutrients) caused a shift towards a net autotrophic microbial metabolism by increasing the net production of oxygen by the benthic and decreasing the net consumption of oxygen by the planktonic microbial community. In contrast, the addition of algal exudates decreased the net primary production by the benthic communities and increased the net consumption of oxygen by the planktonic microbial community thereby resulting in a shift towards net heterotrophic community metabolism. When scaled up to the reef habitat, exudate-induced effects on microbial respiration did not outweigh the high oxygen production rates of benthic algae, such that reef areas dominated with benthic primary

  1. Estimating fish swimming metrics and metabolic rates with accelerometers: the influence of sampling frequency.

    PubMed

    Brownscombe, J W; Lennox, R J; Danylchuk, A J; Cooke, S J

    2018-06-21

    Accelerometry is growing in popularity for remotely measuring fish swimming metrics, but appropriate sampling frequencies for accurately measuring these metrics are not well studied. This research examined the influence of sampling frequency (1-25 Hz) with tri-axial accelerometer biologgers on estimates of overall dynamic body acceleration (ODBA), tail-beat frequency, swimming speed and metabolic rate of bonefish Albula vulpes in a swim-tunnel respirometer and free-swimming in a wetland mesocosm. In the swim tunnel, sampling frequencies of ≥ 5 Hz were sufficient to establish strong relationships between ODBA, swimming speed and metabolic rate. However, in free-swimming bonefish, estimates of metabolic rate were more variable below 10 Hz. Sampling frequencies should be at least twice the maximum tail-beat frequency to estimate this metric effectively, which is generally higher than those required to estimate ODBA, swimming speed and metabolic rate. While optimal sampling frequency probably varies among species due to tail-beat frequency and swimming style, this study provides a reference point with a medium body-sized sub-carangiform teleost fish, enabling researchers to measure these metrics effectively and maximize study duration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Comment on Chem. Phys. Lett. 371 (2003) 568: Barrier height for dissociation of acetaldehyde, CH 3CHO → CH 3 + HCO, in the triplet state T 1

    NASA Astrophysics Data System (ADS)

    Robert Huber, J.

    2003-08-01

    Based on recently reported experimental results from various groups, the barrier height (or transition state energy) for the T 1 dissociation of acetaldehyde, CH 3CHO → CH 3 + HCO, is determined to lie between 12.3 and 12.9 kcal mol -1. This result is compared with predictions from recent ab initio calculations.

  3. Metabolic scope and interspecific competition in sculpins of Greenland are influenced by increased temperatures due to climate change.

    PubMed

    Seth, Henrik; Gräns, Albin; Sandblom, Erik; Olsson, Catharina; Wiklander, Kerstin; Johnsson, Jörgen I; Axelsson, Michael

    2013-01-01

    Ongoing climate change has led to an increase in sea surface temperatures of 2-4°C on the west coast of Greenland. Since fish are ectothermic, metabolic rate increases with ambient temperature. This makes these animals particularly sensitive to changes in temperature; subsequently any change may influence their metabolic scope, i.e. the physiological capacity to undertake aerobically challenging activities. Any temperature increase may thus disrupt species-specific temperature adaptations, at both the molecular level as well as in behavior, and concomitant species differences in the temperature sensitivity may shift the competitive balance among coexisting species. We investigated the influence of temperature on metabolic scope and competitive ability in three species of marine sculpin that coexist in Greenland coastal waters. Since these species have different distribution ranges, we hypothesized that there should be a difference in their physiological response to temperature; hence we compared their metabolic scope at three temperatures (4, 9 and 14°C). Their competitive ability at the ambient temperature of 9°C was also tested in an attempt to link physiological capacity with behaviour. The Arctic staghorn sculpin, the species with the northernmost distribution range, had a lower metabolic scope in the higher temperature range compared to the other two species, which had similar metabolic scope at the three temperatures. The Arctic staghorn sculpin also had reduced competitive ability at 9°C and may thus already be negatively affected by the current ocean warming. Our results suggest that climate change can have effects on fish physiology and interspecific competition, which may alter the species composition of the Arctic fish fauna.

  4. Effect of oxidoreduction potential on aroma biosynthesis by lactic acid bacteria in nonfat yogurt.

    PubMed

    Martin, F; Cachon, R; Pernin, K; De Coninck, J; Gervais, P; Guichard, E; Cayot, N

    2011-02-01

    The aim of this study was to investigate the effect of oxidoreduction potential (Eh) on the biosynthesis of aroma compounds by lactic acid bacteria in non-fat yogurt. The study was done with yogurts fermented by Lactobacillus bulgaricus and Streptococcus thermophilus. The Eh was modified by the application of different gaseous conditions (air, nitrogen, and nitrogen/hydrogen). Acetaldehyde, dimethyl sulfide, diacetyl, and pentane-2,3-dione, as the major endogenous odorant compounds of yogurt, were chosen as tracers for the biosynthesis of aroma compounds by lactic acid bacteria. Oxidative conditions favored the production of acetaldehyde, dimethyl sulfide, and diketones (diacetyl and pentane-2,3-dione). The Eh of the medium influences aroma production in yogurt by modifying the metabolic pathways of Lb. bulgaricus and Strep. thermophilus. The use of Eh as a control parameter during yogurt production could permit the control of aroma formation. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Low-intensity lasers, modern filling materials, and bonding systems influence on mineral metabolism of hard dental tissues

    NASA Astrophysics Data System (ADS)

    Kunin, Anatoly A.; Yesaulenko, I. E.; Zoibelmann, M.; Pankova, Svetlana N.; Ippolitov, Yu. A.; Oleinik, Olga I.; Popova, T. A.; Koretskaya, I. V.; Shumilovitch, Bogdan R.; Podolskaya, Elana E.

    2001-10-01

    One of the main reasons of low quality filling is breaking Ca-P balance in hard tissues. Our research was done with the purpose of studying the influence of low intensity lasers, diodic radiation, the newest filling and bonding systems on the processes of mineral metabolism in hard dental tissues while filling a tooth. 250 patients having caries and its compli-cations were examined and treated. Our complex research included: visual and instrumental examination, finding out the level of oral cavity hygiene, acid enamel biopsy, scanning electronic microscopy and X-ray spectrum microanalysis. Filling processes may produce a negative effect on mineral metabolism of hard dental tissues the latter is less pronounced when applying fluoride-containing filling materials with bonding systems. It has also been found that bonding dentin and enamel systems are designed for both a better filling adhesion (i.e. mechanical adhesion) and migration of useful microelements present in them by their sinking into hard dental tissues (i.e. chemical adhesion). Our research showed a positive influence of low intensity laser and diodic beams accompanying the use of modern filling and bonding systems on mineral metabolism of hard dental tissues.

  6. Laboratory Studies on the Formation of Three C2H4O Isomers-Acetaldehyde (CH3CHO), Ethylene Oxide (c-C2H4O), and Vinyl Alcohol (CH2CHOH)-in Interstellar and Cometary Ices

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Osamura, Yoshihiro; Lebar, Matt D.; Kaiser, Ralf I.

    2005-11-01

    Laboratory experiments were conducted to unravel synthetic routes to form three C2H4O isomers-acetaldehyde (CH3CHO), ethylene oxide (c-C2H4O), and vinyl alcohol (CH2CHOH)-in extraterrestrial ices via electronic energy transfer processes initiated by electrons in the track of MeV ion trajectories. Here we present the results of electron irradiation on a 2:1 mixture of carbon dioxide (CO2) and ethylene (C2H4). Our studies suggest that suprathermal oxygen atoms can add to the carbon-carbon π bond of an ethylene molecule to form initially an oxirene diradical (addition to one carbon atom) and the cyclic ethylene oxide molecule (addition to two carbon atoms) at 10 K. The oxirene diradical can undergo a [1, 2]-H shift to the acetaldehyde molecule. Both the ethylene oxide and the acetaldehyde isomers can be stabilized in the surrounding ice matrix. To a minor amount, suprathermal oxygen atoms can insert into a carbon-hydrogen bond of the ethylene molecule, forming vinyl alcohol. Once these isomers have been synthesized inside the ice layers of the coated grains in cold molecular clouds, the newly formed molecules can sublime as the cloud reaches the hot molecular core stage. These laboratory investigations help to explain astronomical observations by Nummelin et al. and Ikeda et al. toward massive star-forming regions and hot cores, where observed fractional abundances of these isomers are higher than can be accounted for by gas-phase reactions alone. Similar synthetic routes could help explain the formation of acetaldehyde and ethylene oxide in comet C/1995 O1 (Hale-Bopp) and also suggest a presence of both isomers in Titan's atmosphere.

  7. Malondialdehyde-acetaldehyde (MAA) adducted surfactant protein induced lung inflammation is mediated through scavenger receptor a (SR-A1).

    PubMed

    Sapkota, Muna; DeVasure, Jane M; Kharbanda, Kusum K; Wyatt, Todd A

    2017-02-13

    Co-exposure to cigarette smoke and alcohol leads to the generation of high concentrations of acetaldehyde and malondialdehyde in the lung. These aldehydes being highly electrophilic in nature react with biologically relevant proteins such as surfactant protein D (SPD) through a Schiff base reaction to generate SPD adducted malondialdehyde-acetaldehyde adduct (SPD-MAA) in mouse lung. SPD-MAA results in an increase in lung pro-inflammatory chemokine, keratinocyte chemoattractant (KC), and the recruitment of lung lavage neutrophils. Previous in vitro studies in bronchial epithelial cells and macrophages show that scavenger receptor A (SR-A1/CD204) is a major receptor for SPD-MAA. No studies have yet examined the in vivo role of SR-A1 in MAA-mediated lung inflammation. Therefore, we hypothesize that in the absence of SR-A1, MAA-induced inflammation in the lung is reduced or diminished. To test this hypothesis, C57BL/6 WT and SR-A1 KO mice were nasally instilled with 50 μg/mL of SPD-MAA for 3 weeks (wks). After 3 weeks, bronchoalveolar lavage (BAL) fluid was collected and assayed for a total cell count, a differential cell count and CXCL1 (KC) chemokine. Lung tissue sections were stained with hematoxylin and eosin (H&E) and antibodies to MAA adduct. Results showed that BAL cellularity and influx of neutrophils were decreased in SR-A1 KO mice as compared to WT following repetitive SPD-MAA exposure. MAA adduct staining in the lung epithelium was decreased in SR-A1 KO mice. In comparison to WT, no increase in CXCL1 was observed in BAL fluid from SR-A1 KO mice over time. Overall, the data demonstrate that SR-A1/CD204 plays an important role in SPD-MAA induced inflammation in lung.

  8. Metabolic effects of artificial environments

    NASA Technical Reports Server (NTRS)

    Jordan, J. P.

    1971-01-01

    The mechanisms by which inert gases influence metabolism were investigated from several viewpoints. Groups of rats were exposed at the thermal neutral temperature of the respective mixtures, to normoxic (P sub A 02 = 100 mm Hq) environments with argon, helium or nitrogen as the diluent at a total pressure of one atmosphere. The possible influence of diluent gases on oxygen transport to the cell was examined with hypoxic (P sub A O2 = 70 mm Hg) mixtures of the same diluent gases. Metabolic measurements included food, water, and oxygen consumption, CO2 production, hematocrit and the rate C-14O2 of expiration subsequent to intraperitoneal injection of acetate-1-C-14 or glucose UL-C-14. Argon-exposed animals showed a consistently decreased metabolic rate while, on the other hand, helium-exposed rats did not significantly alter metabolic rate relative to nitrogen. Certain indices, including acetate and glucose utilization, suggested that helium attenuated the imposed hypoxia at the cellular level while argon facilitated it as compared with nitrogen. These results suggest that metabolic influence of helium is largely thermal in nature while argon has a significant direct metabolic effect and that diluent gases may selectively influence oxygen availability to the interior of the cell.

  9. Integrated phenotypic-genotypic approach to understand the influence of ultrasound on metabolic response of Lactobacillus sakei.

    PubMed

    Ojha, K Shikha; Burgess, Catherine M; Duffy, Geraldine; Kerry, Joseph P; Tiwari, Brijesh K

    2018-01-01

    The lethal effects of soundwaves on a range of microorganisms have been known for almost a century whereas, the use of ultrasound to promote or control their activity is much more recent. Moreover, the fundamental molecular mechanism influencing the behaviour of microorganisms subjected to ultrasonic waves is not well established. In this study, we investigated the influence of ultrasonic frequencies of 20, 45, 130 and 950 kHz on growth kinetics of Lactobacillus sakei. A significant increase in the growth rate of L. sakei was observed following ultrasound treatment at 20 kHz despite the treatment yielding a significant reduction of ca. 3 log cfu/mL in cells count. Scanning electron microscopy showed that ultrasound caused significant changes on the cell surface of L. sakei culture with the formation of pores "sonoporation". Phenotypic microarrays showed that all ultrasound treated L. sakei after exposure to various carbon, nitrogen, phosphorus and sulphur sources had significant variations in nutrient utilisation. Integration of this phenotypic data with the genome of L. sakei revealed that various metabolic pathways were being influenced by the ultrasound treatments. Results presented in this study showed that the physiological response of L. sakei in response to US is frequency dependent and that it can influence metabolic pathways. Hence, ultrasound treatments can be employed to modulate microbial activity for specialised applications.

  10. Integrated phenotypic-genotypic approach to understand the influence of ultrasound on metabolic response of Lactobacillus sakei

    PubMed Central

    Ojha, K. Shikha; Burgess, Catherine M.; Duffy, Geraldine; Kerry, Joseph P.

    2018-01-01

    The lethal effects of soundwaves on a range of microorganisms have been known for almost a century whereas, the use of ultrasound to promote or control their activity is much more recent. Moreover, the fundamental molecular mechanism influencing the behaviour of microorganisms subjected to ultrasonic waves is not well established. In this study, we investigated the influence of ultrasonic frequencies of 20, 45, 130 and 950 kHz on growth kinetics of Lactobacillus sakei. A significant increase in the growth rate of L. sakei was observed following ultrasound treatment at 20 kHz despite the treatment yielding a significant reduction of ca. 3 log cfu/mL in cells count. Scanning electron microscopy showed that ultrasound caused significant changes on the cell surface of L. sakei culture with the formation of pores “sonoporation”. Phenotypic microarrays showed that all ultrasound treated L. sakei after exposure to various carbon, nitrogen, phosphorus and sulphur sources had significant variations in nutrient utilisation. Integration of this phenotypic data with the genome of L. sakei revealed that various metabolic pathways were being influenced by the ultrasound treatments. Results presented in this study showed that the physiological response of L. sakei in response to US is frequency dependent and that it can influence metabolic pathways. Hence, ultrasound treatments can be employed to modulate microbial activity for specialised applications. PMID:29370210

  11. Influence of oxygen therapy on glucose-lactate metabolism after diffuse brain injury.

    PubMed

    Reinert, Michael; Schaller, Benoit; Widmer, Hans Rudolf; Seiler, Rolf; Bullock, Ross

    2004-08-01

    O2 influences dialysate glucose and lactate levels in injured brain tissue. Using an FiO2 of 1 influences brain metabolism in such a way that lactate is significantly reduced and glucose significantly increased. No changes in dialysate glucose and lactate values were found in the noninjured brain.

  12. Interesting electron storage phenomenon in the spherical Ag/TiO{sub 2} nanocomposites and its application for the decomposition of acetaldehyde in the dark

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Xinyan; State Key Laboratory of Electroanalytical Chemistry, c/o Engineering Laboratory for Modern Analytical Techniques, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022; Wu, Tongshun

    2016-01-15

    Highlights: • The Ag/TiO{sub 2} composites have been prepared by a facile solvothermal method. • The photogenerated charges transfer behaviors between the Ag and TiO{sub 2}. • The Ag/TiO{sub 2} composites can store photogenerated electrons for a relative long time. • The Ag/TiO{sub 2} composite could be further used to decompose acetaldehyde in the dark. - Abstract: Ag/TiO{sub 2} nanocomposite has been prepared by a facile one-step low-temperature solvothermal method. The powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements have been used to characterize the detailed structure of the as-synthesized nanocomposite and the results indicate that the nanocompoistemore » is with the spherical structure and Ag and TiO{sub 2} nanoparticles are homogeneously dispersed in the sphere. Surface photovoltage (SPV) and transient photovoltage (TPV) techniques were used to further investigate the charge transfer behavior between the TiO{sub 2} and Ag in this composite material, and the results reveal that the nanocomposites could store the electrons for a relative long time even under air. Furthermore, these stored electrons in the nanocomposites have been successfully applied to decompose the acetaldehyde in the dark.« less

  13. Influence of cellular and paracellular conductance patterns on epithelial transport and metabolism.

    PubMed Central

    Essig, A

    1982-01-01

    Theoretical analysis of transepithelial active Na transport is often based on equivalent electrical circuits comprising discrete parallel active and passive pathways. Recent findings show, however, that Na+ pumps are distributed over the entire basal lateral surface of epithelial cells. This suggests that Na+ that has been actively transported into paracellular channels may to some extent return to the apical (mucosal) bathing solution, depending on the relative conductances of the pathways via the tight junctions and the lateral intercellular spaces. Such circulation, as well as the relative conductance of cellular and paracellular pathways, may have an important influence on the relationships between parameters of transcellular and transepithelial active transport and metabolism. These relationships were examined by equivalent circuit analysis of active Na transport, Na conductance, the electromotive force of Na transport, the "stoichiometry" of transport, and the degree of coupling of transport to metabolism. Although the model is too crude to permit precise quantification, important qualitative differences are predicted between "loose" and "tight" epithelia in the absence and presence of circulation. In contrast, there is no effect on the free energy of metabolic reaction estimated from a linear thermodynamic formalism. Also of interest are implications concerning the experimental evaluation of passive paracellular conductance following abolition of active transport, and the use of the cellular voltage-divider ratio to estimate the relative conductances of apical and basal lateral plasma membranes. PMID:6284264

  14. Alcohol intake and folate antagonism via CYP2E1 and ALDH1: Effects on oral carcinogenesis

    PubMed Central

    Hwang, Phillip H.; Lian, Lisa; Zavras, Athanasios I.

    2011-01-01

    The interaction of folate and alcohol consumption has been shown to have an antagonistic effect on the risk of oral cancer. Studies have demonstrated that increased intake of folate decreases the risk of oral cancer, while greater alcohol consumption has an opposite effect. However, what is poorly understood is the biological interaction of these two dietary factors in relation to carcinogenesis. We hypothesize that cytochrome P450 2E1 (CYP2E1) and the family of aldehyde dehydrogenase 1 (ALDH1) enzymes may play a causal role in the occurrence of oral cancer. Chronic and high alcohol use has been implicated in the induction of CYP2E1, which oxidizes ethanol to acetaldehyde. Acetaldehyde is a known carcinogen. As the first metabolite of ethanol, it has been shown to interfere with DNA methylation, synthesis and repair, as well as bind to protein and DNA to form stable adducts, which lead to the eventual formation of damaged DNA and cell proliferation. Studies using liver cells have demonstrated that S-adenosyl methionine (SAM), which is a product of folate metabolism, regulates the expression and catalytic activity of CYP2E1. Our first hypothesis is that as increased levels of folate lead to higher concentrations of SAM, SAM antagonizes the expression of CYP2E1, which results in decreased conversion of ethanol into acetaldehyde. Thus, the lower levels of acetaldehyde may lower risk of oral cancer. There are also two enzymes within the ALDH1 family that play an important role both in ethanol metabolism and the folate one-carbon pathway. The first, ALDH1A1, converts acetaldehyde into its non-carcinogenic byproduct, acetate, as part of the second step in the ethanol metabolism pathway. The second, ALDH1L1, also known as FDH, is required for DNA nucleotide biosynthesis, and is upregulated at high concentrations of folate. ALDH1L1 appears to be a chief regulator of cellular metabolism as it is strongly downregulated at certain physiological and pathological conditions

  15. Asymmetric organocatalyzed Michael addition of nitromethane to a 2-oxoindoline-3-ylidene acetaldehyde and the three one-pot sequential synthesis of (-)-horsfiline and (-)-coerulescine.

    PubMed

    Mukaiyama, Takasuke; Ogata, Kento; Sato, Itaru; Hayashi, Yujiro

    2014-10-13

    (-)-Horsfiline and (-)-coerulescine were synthesized through three one-pot operations in 33 and 46% overall yield, respectively. Key to the success was the efficient use of a diarylprolinol silyl ether to catalyze the asymmetric Michael addition of nitromethane to a 2-oxoindoline-3-ylidene acetaldehyde. This allowed the all-carbon quaternary, spirocyclic carbon stereocenter to be constructed in good yield with excellent enantioselectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: assessment of the effects on first-pass metabolism of ethanol.

    PubMed

    Lee, Shou-Lun; Lee, Yung-Pin; Wu, Min-Li; Chi, Yu-Chou; Liu, Chiu-Ming; Lai, Ching-Long; Yin, Shih-Jiun

    2015-05-01

    Previous studies have reported that aspirin significantly reduced the first-pass metabolism (FPM) of ethanol in humans thereby increasing adverse effects of alcohol. The underlying causes, however, remain poorly understood. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition profiles by aspirin and its major metabolite salicylate of ethanol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and acetaldehyde oxidation by ALDH1A1 and ALDH2, at pH 7.5 and 0.5 mM NAD(+). Competitive inhibition pattern was found to be a predominant type among the ADHs and ALDHs studied, although noncompetitive and uncompetitive inhibitions were also detected in a few cases. The inhibition constants of salicylate for the ADHs and ALDHs were considerably lower than that of aspirin with the exception of ADH1A that can be ascribed to a substitution of Ala-93 at the bottom of substrate pocket as revealed by molecular docking experiments. Kinetic inhibition equation-based simulations show at higher therapeutic levels of blood plasma salicylate (1.5 mM) that the decrease of activities at 2-10 mM ethanol for ADH1A/ADH2 and ADH1B2/ADH1B3 are predicted to be 75-86% and 31-52%, respectively, and that the activity decline for ALDH1A1 and ALDH2 at 10-50 μM acetaldehyde to be 62-73%. Our findings suggest that salicylate may substantially inhibit hepatic FPM of alcohol at both the ADH and ALDH steps when concurrent intaking aspirin. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Radicals derived from acetaldehyde and vinyl alcohol.

    PubMed

    Estep, Marissa L; Morgan, W James; Winkles, Alexander T; Abbott, Adam S; Villegas-Escobar, Nery; Mullinax, J Wayne; Turner, Walter E; Wang, Xiao; Turney, Justin M; Schaefer, Henry F

    2017-10-18

    Vinyl alcohol and acetaldehyde are isoelectronic products of incomplete butanol combustion. Along with the radicals resulting from the removal of atomic hydrogen or the hydroxyl radical, these species are studied here using ab initio methods as complete as coupled cluster theory with single, double, triple, and perturbative quadruple excitations [CCSDT(Q)], with basis sets as large as cc-pV5Z. The relative energies provided herein are further refined by including corrections for relativistic effects, the frozen core approximation, and the Born-Oppenheimer approximation. The effects of anharmonic zero-point vibrational energies are also treated. The syn conformer of vinyl alcohol is predicted to be lower in energy than the anti conformer by 1.1 kcal mol -1 . The alcoholic hydrogen of syn-vinyl alcohol is found to be the easiest to remove, requiring 84.4 kcal mol -1 . Five other radicals are also carefully considered, with four conformers investigated for the 1-hydroxyvinyl radical. Beyond energetics, we have conducted an overhaul of the spectroscopic literature for these species. Our results also provide predictions for fundamental modes yet to be reported experimentally. To our knowledge, the ν 3 (3076 cm -1 ) and ν 4 (2999 cm -1 ) C-H stretches for syn-vinyl alcohol and all but one of the vibrational modes for anti-vinyl alcohol (ν 1 -ν 14 ) are yet to be observed experimentally. For the acetyl radical, ν 6 (1035 cm -1 ), ν 11 (944 cm -1 ), ν 12 (97 cm -1 ), and accounting for our changes to the assignment of the 1419.9 cm -1 experimental mode, ν 10 (1441 cm -1 ), are yet to be observed. We have predicted these unobserved fundamentals and reassigned the experimental 1419.9 cm -1 frequency in the acetyl radical to ν 4 rather than to ν 10 . Our work also strongly supports reassignment of the ν 10 and ν 11 fundamentals of the vinoxy radical. We suggest that the bands assigned to the overtones of these fundamentals were in fact combination bands. Our

  18. Altered drug metabolism during pregnancy: Hormonal regulation of drug-metabolizing enzymes

    PubMed Central

    Jeong, Hyunyoung

    2013-01-01

    Importance of the field Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Areas covered in this review Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are likely responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes, thus potentially responsible for altered drug metabolism during pregnancy. What the reader will gain The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of drug-metabolizing enzymes. Take home message In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy. PMID:20367533

  19. The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

    NASA Astrophysics Data System (ADS)

    Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

    2016-09-01

    Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L-1, reaching 80% and 100% inhibition at 10 mg L-1 and 50 mg L-1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry.

  20. The fungicide triadimefon affects beer flavor and composition by influencing Saccharomyces cerevisiae metabolism

    PubMed Central

    Kong, Zhiqiang; Li, Minmin; An, Jingjing; Chen, Jieying; Bao, Yuming; Francis, Frédéric; Dai, Xiaofeng

    2016-01-01

    Despite the fact that beer is produced on a large scale, the effects of pesticide residues on beer have been rarely investigated. In this study, we used micro-brewing settings to determine the effect of triadimefon on the growth of Saccharomyces cerevisiae and beer flavor. The yeast growth in medium was significantly inhibited (45%) at concentrations higher than 5 mg L−1, reaching 80% and 100% inhibition at 10 mg L−1 and 50 mg L−1, respectively. There were significant differences in sensory quality between beer samples fermented with and without triadimefon based on data obtained with an electronic tongue and nose. Such an effect was most likely underlain by changes in yeast fermentation activity, including decreased utilization of maltotriose and most amino acids, reduced production of isobutyl and isoamyl alcohols, and increased ethyl acetate content in the fungicide treated samples. Furthermore, yeast metabolic profiling by phenotype microarray and UPLC/TOF-MS showed that triadimefon caused significant changes in the metabolism of glutathione, phenylalanine and sphingolipids, and in sterol biosynthesis. Thus, triadimefon negatively affects beer sensory qualities by influencing the metabolic activity of S. cerevisiae during fermentation, emphasizing the necessity of stricter control over fungicide residues in brewing by the food industry. PMID:27629523

  1. Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes.

    PubMed

    Jeong, Hyunyoung

    2010-06-01

    Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.

  2. Acute Ethanol Causes Hepatic Mitochondrial Depolarization in Mice: Role of Ethanol Metabolism

    PubMed Central

    Zhong, Zhi; Ramshesh, Venkat K.; Rehman, Hasibur; Liu, Qinlong; Theruvath, Tom P.; Krishnasamy, Yasodha; Lemasters, John J.

    2014-01-01

    steatosis and increased mitochondrial respiration. Onset of this mitochondrial depolarization is linked, at least in part, to metabolism of ethanol to acetaldehyde. PMID:24618581

  3. [Influence of conjugated linoleic acids on metabolic processes in cells and tissues].

    PubMed

    Siwiec, Ewa; Stachowska, Ewa

    2017-01-01

    Conjugated linoleic acids (CLA) are constitutional and geometric isomers of this acid. The most commonly consumed geometric isomers are cis-9,trans-11 (c9, t11) CLA and trans-10, cis-12 (t10,c12) CLA. These isomers together with trans-9,trans-11 CLA and trans-10,trans-12 CLA constitute about 90% of all CLA in natural products. Different structure of the isomers affects their functions in the body. Differences in the effects on organs and tissues are sometimes small and sometimes opposed, sometimes the isomers work synergistically. Diverse influence has been shown mainly in neoplastic processes and lipid metabolism. For example, differences in inhibition of proliferation of prostate cancer cells are explained by different pathways: t10,c12 CLA acts on apoptosis and cell cycle control genes, while c9,t11 CLA regulates genes involved in metabolism of arachidonic acid with subsequent impairment of eicosanoids synthesis. Other studies have shown that t10,c12 CLA, but not c9,t11 CLA, can induce fat reduction in adipose tissue and apoptosis of adipocytes in mice.

  4. Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia

    PubMed Central

    Gosadi, Ibrahim M.

    2016-01-01

    Metabolic syndrome (MS) is a combination of factors that increases the risk of cardiovascular atherosclerotic diseases including diabetes, obesity, dyslipidemia, and high blood pressure. Cardiovascular diseases are one of the leading causes of death in the adult Saudi population where the increase in cardiovascular-related mortality is augmented by the rise in the prevalence of MS. Metabolic syndrome is a multi-factorial disorder influenced by interactions between genetic and environmental components. This review aims to provide a comprehensive assessment of studied environmental and genetic factors explaining the prevalence of MS in the Kingdom of Saudi Arabia. Additionally, this review aims to illustrate factors related to the population genetics of Saudi Arabia, which might explain a proportion of the prevalence of MS. PMID:26739969

  5. Elucidating the influence of praziquantel nanosuspensions on the in vivo metabolism of Taenia crassiceps cysticerci.

    PubMed

    Silva, Luciana Damacena; Arrúa, Eva Carolina; Pereira, Dayanne Amaral; Fraga, Carolina Miguel; Costa, Tatiane Luiza da; Hemphill, Andrew; Salomon, Claudio Javier; Vinaud, Marina Clare

    2016-09-01

    The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100nm, while P188- and P407-based nanosuspensions had particle sizes of 74nm and 285nm, respectively. The zeta potential was -8.1, -8.6, and -13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Epigenetics and Cellular Metabolism

    PubMed Central

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  7. Simultaneous determination of airborne acetaldehyde, acetone, 2-butanone, and cyclohexanone using sampling tubes with 2,4-dinitrophenylhydrazine-coated solid sorbent.

    PubMed

    Binding, N; Schilder, K; Czeschinski, P A; Witting, U

    1998-08-01

    The 2,4-dinitrophenylhydrazine (2,4-DNPH) derivatization method mainly used for the determination of airborne formaldehyde was extended for acetaldehyde, acetone, 2-butanone, and cyclohexanone, the next four carbonyl compounds of industrial importance. Sampling devices and sampling conditions were adjusted for the respective limit value regulations. Analytical reliability criteria were established and compared to those of other recommended methods. With a minimum analytical range from one tenth to the 3-fold limit value in all cases and with relative standard deviations below 5%, the adjusted method meets all requirements for the reliable quantification of the four compounds in workplace air as well as in ambient air.

  8. Association between in vivo alcohol metabolism and genetic variation in pathways that metabolize the carbon skeleton of ethanol and NADH reoxidation in the Alcohol Challenge Twin Study

    PubMed Central

    Lind, Penelope A; Macgregor, Stuart; Heath, Andrew C; Madden, Pamela AF; Montgomery, Grant W; Martin, Nicholas G; Whitfield, John B

    2013-01-01

    Background Variation in alcohol metabolism affects the duration of intoxication and alcohol use. While the majority of genetic association studies investigating variation in alcohol metabolism have focused on polymorphisms in alcohol or aldehyde dehydrogenases, we have now tested for association with genes in alternative metabolic pathways that catalyze the carbon skeleton of ethanol and NADH reoxidation. Methods 950 single nucleotide polymorphisms (SNPs) spanning 14 genes (ACN9, ACSS1, ACSS2, ALDH1A1, CAT, CYP2E1, GOT1, GOT2, MDH1, MDH2, SLC25A10, SLC25A11, SLC25A12, SLC25A13) were genotyped in 352 young adults who participated in an alcohol challenge study. Traits tested were blood and breath alcohol concentration, peak alcohol concentration and rates of alcohol absorption and elimination. Allelic association was tested using quantitative univariate and multivariate methods. Results A CYP2E1 promoter SNP (rs4838767, minor allele frequency 0.008) exceeded the threshold for study-wide significance (4.01 × 10−5) for two early blood alcohol concentration (BAC), eight breath alcohol concentration (BrAC) measures and the peak BrAC. For each phenotype the minor C-allele was related to a lower alcohol concentration, most strongly for the fourth BrAC (P = 2.07 × 10−7) explaining ~8% of the phenotypic variance. We also observed suggestive patterns of association with variants in ALDH1A1 and on chromosome 17 near SLC25A11 for aspects of blood and breath alcohol metabolism. A SNP upstream of GOT1 (rs2490286) reached study-wide significance for multivariate BAC metabolism (P = 0.000040). Conclusions Overall, we did not find strong evidence that variation in genes coding for proteins that further metabolize the carbon backbone of acetaldehyde, or contribute to mechanisms for regenerating NAD from NADH, affects alcohol metabolism in our European-descent subjects. However, based on the breath alcohol data, variation in the promoter of CYP2E1 may play a role in pre

  9. Association between in vivo alcohol metabolism and genetic variation in pathways that metabolize the carbon skeleton of ethanol and NADH reoxidation in the alcohol challenge twin study.

    PubMed

    Lind, Penelope A; Macgregor, Stuart; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant W; Martin, Nicholas G; Whitfield, John B

    2012-12-01

    Variation in alcohol metabolism affects the duration of intoxication and alcohol use. While the majority of genetic association studies investigating variation in alcohol metabolism have focused on polymorphisms in alcohol or aldehyde dehydrogenases, we have now tested for association with genes in alternative metabolic pathways that catalyze the carbon skeleton of ethanol (EtOH) and NADH reoxidation. Nine hundred fifty single nucleotide polymorphisms (SNPs) spanning 14 genes (ACN9, ACSS1, ACSS2, ALDH1A1, CAT, CYP2E1, GOT1, GOT2, MDH1, MDH2, SLC25A10, SLC25A11, SLC25A12, SLC25A13) were genotyped in 352 young adults who participated in an alcohol challenge study. Traits tested were blood alcohol concentration (BAC), breath alcohol concentration (BrAC), peak alcohol concentration, and rates of alcohol absorption and elimination. Allelic association was tested using quantitative univariate and multivariate methods. A CYP2E1 promoter SNP (rs4838767, minor allele frequency 0.008) exceeded the threshold for study-wide significance (4.01 × 10(-5) ) for 2 early BAC, 8 BrAC measures, and the peak BrAC. For each phenotype, the minor C allele was related to a lower alcohol concentration, most strongly for the fourth BrAC (p = 2.07 × 10(-7) ) explaining ~8% of the phenotypic variance. We also observed suggestive patterns of association with variants in ALDH1A1 and on chromosome 17 near SLC25A11 for aspects of blood and breath alcohol metabolism. An SNP upstream of GOT1 (rs2490286) reached study-wide significance for multivariate BAC metabolism (p = 0.000040). Overall, we did not find strong evidence that variation in genes coding for proteins that further metabolize the carbon backbone of acetaldehyde, or contribute to mechanisms for regenerating NAD from NADH, affects alcohol metabolism in our European-descent subjects. However, based on the breath alcohol data, variation in the promoter of CYP2E1 may play a role in preabsorptive or early hepatic alcohol metabolism

  10. The influence of increased distal loading on metabolic cost, efficiency, and kinematics of roller ski skating.

    PubMed

    Bolger, Conor M; Bessone, Veronica; Federolf, Peter; Ettema, Gertjan; Sandbakk, Øyvind

    2018-01-01

    The purpose of the present study was to examine the influence of increased loading of the roller ski on metabolic cost, gross efficiency, and kinematics of roller ski skating in steep and moderate terrain, while employing two incline-specific techniques. Ten nationally ranked male cross-country skiers were subjected to four 7-minute submaximal intervals, with 0, 0.5, 1.0, and 1.5 kg added beneath the roller-ski in a randomized order. This was done on two separate days, with the G2 skating at 12% incline and 7 km/h speed and G3 skating at 5% incline and 14 km/h speed, respectively. At 12% incline, there was a significant increase in metabolic rate and a decrease in gross efficiency with added weight (P<0.001 and P = 0.002). At 5% incline, no change in metabolic rate or gross efficiency was found (P = 0.89 and P = 0.11). Rating of perceived exertion (RPE) increased gradually with added weight at both inclines (P>0.05). No changes in cycle characteristics were observed between the different ski loadings at either incline, although the lateral and vertical displacements of the foot/skis were slightly altered at 12% incline with added weight. In conclusion, the present study demonstrates that increased loading of the ski increases the metabolic cost and reduces gross efficiency during steep uphill roller skiing in G2 skating, whereas no significant effect was revealed when skating on relatively flat terrain in G3. Cycle characteristics remained unchanged across conditions at both inclines, whereas small adjustments in the displacement of the foot coincided with the efficiency changes in uphill terrain. The increased RPE values with added ski-weight at both inclines indicates that other factors than those measured here could have influenced effort and/or fatigue when lifting a heavier ski.

  11. The broadband rotational spectrum of fully deuterated acetaldehyde (CD3CDO) in a CW supersonic expansion

    NASA Astrophysics Data System (ADS)

    Zaleski, Daniel P.; Duan, Chuanxi; Carvajal, Miguel; Kleiner, Isabelle; Prozument, Kirill

    2017-12-01

    The broadband pure rotational spectra of CD3CDO, 13CD3CDO, CD313CDO, and CD3CD18O have been recorded using a BrightSpec W-Band (75-110 GHz) chirped-pulse Fourier transform millimeter wave (CP-FTmmW) spectrometer. The sample was enriched with deuterium, whereas the 13C and 18O isotopologues were observed in natural abundance (with respect to the enriched fully deuterated parent containing 12C and 16O). The analysis of the spectra is described and the derived molecular constants are compared to those of known acetaldehyde isotopologues. Furthermore, we have demonstrated the ability to record rotational spectra in a steady-state "CW" supersonic expansion with a duty cycle of 80%. The advantages and limitations of the segmented chirp spectrometer coupled with a CW molecular source as well as design of the vacuum and pumping system are discussed.

  12. Individual condition, standard metabolic rate, and rearing temperature influence steelhead and rainbow trout (Oncorhynchus mykiss) life histories

    Treesearch

    Matthew R. Sloat; Gordon H. Reeves

    2014-01-01

    We reared juvenile Oncorhychus mykiss with low and high standard metabolic rates (SMR) under alternative thermal regimes to determine how these proximate factors influence life histories in a partially migratory salmonid fish. High SMR significantly decreased rates of freshwater maturation and increased rates of smoltification in females, but not...

  13. Hormonal alterations in PCOS and its influence on bone metabolism.

    PubMed

    Krishnan, Abhaya; Muthusami, Sridhar

    2017-02-01

    According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to the Indian Council of Medical Research (ICMR). The National Institute of Health has documented that it affects approximately 5 million women of reproductive age in the United States. Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome (PCOS). The influence of various endocrine changes in PCOS women and their relevance to bone remains to be documented. Hormones, which include gonadotrophin-releasing hormone (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio, androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH) and calcitonin are disturbed in PCOS women. These hormones influence bone metabolism in human subjects directly as well as indirectly. The imbalance in these hormones results in increased prevalence of osteoporosis in PCOS women. Limited evidence suggests that the drugs taken during the treatment of PCOS increase the risk of bone fracture in PCOS patients through endocrine disruption. This review is aimed at the identification of the relationship between bone mineral density and hormonal changes in PCOS subjects and identifies potential areas to study bone-related disorders in PCOS women. © 2017 Society for Endocrinology.

  14. Central carbon metabolism influences cellulase production in Bacillus licheniformis.

    PubMed

    Wang, J; Liu, S; Li, Y; Wang, H; Xiao, S; Li, C; Liu, B

    2018-01-01

    Bacillus licheniformis that can produce cellulase including endo glucanase and glucosidase is an important industrial microbe for cellulose degradation. The purpose of this research was to assess the effect of endo glucanase gene bglC and glucosidase gene bglH on the central metabolic flux in B. licheniformis. bglC and bglH were knocked out using homologous recombination method, respectively, and the corresponding knockout strains were obtained for 13 C metabolic flux analysis. A significant change was observed in metabolic fluxes after 13 C metabolic flux ratio analysis. In both of the knockout strains, the increased fluxes of the pentose phosphate pathway and malic enzyme reaction enabled an elevated supply of NADPH which provided enough reducing power for the in vivo synthesis reactions. The fluxes through tricarboxylic acid cycle and anaplerotic reactions increased fast in the two knockout strains, which meant more energy generated. The changed fluxes in central carbon metabolism provided a holistic view of the physiological status in B. licheniformis and possible targets for further strain engineering. Cellulase is very important in the field of agriculture and bioenergy because of its degrading effect on cellulosic biomass. This study presented the effect of central carbon metabolism on cellulase production in Bacillus licheniformis. The study also provided a holistic view of the physiological status in B. licheniformis. The shifted metabolism provided a quantitative evaluation of the biosynthesis of cellulase and a priority ranked target list for further strain engineering. © 2017 The Society for Applied Microbiology.

  15. Eating beyond metabolic need: how environmental cues influence feeding behavior.

    PubMed

    Johnson, Alexander W

    2013-02-01

    Animals use current, past, and projected future states of the organism and the world in a finely tuned system to control ingestion. They must not only deal effectively with current nutrient deficiencies, but also manage energy resources to meet future needs, all within the constraints of the mechanisms of metabolism. Many recent approaches to understanding the control of ingestive behavior distinguish between homeostatic mechanisms concerned with energy balance, and hedonic and incentive processes based on palatability and reward characteristics of food. In this review, I consider how learning about environmental cues influences homeostatic and hedonic brain signals, which may lead to increases in the affective taste properties of food and desire to over consume. Understanding these mechanisms may be critical for elucidating the etiology of the obesity epidemic. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Influence of obesity and metabolic disease on carotid atherosclerosis in patients with coronary artery disease (CordioPrev study)

    USDA-ARS?s Scientific Manuscript database

    Background: Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC...

  17. Pasture-feeding of Charolais steers influences skeletal muscle metabolism and gene expression.

    PubMed

    Cassar-Malek, I; Jurie, C; Bernard, C; Barnola, I; Micol, D; Hocquette, J-F

    2009-10-01

    Extensive beef production systems on pasture are promoted to improve animal welfare and beef quality. This study aimed to compare the influence on muscle characteristics of two management approaches representative of intensive and extensive production systems. One group of 6 Charolais steers was fed maize-silage indoors and another group of 6 Charolais steers grazed on pasture. Activities of enzymes representative of glycolytic and oxidative (Isocitrate dehydrogenase [ICDH], citrate synthase [CS], hydroxyacyl-CoA dehydrogenase [HAD]) muscle metabolism were assessed in Rectus abdominis (RA) and Semitendinosus (ST) muscles. Activities of oxidative enzymes ICDH, CS and HAD were higher in muscles from grazing animals demonstrating a plasticity of muscle metabolism according to the production and feeding system. Gene expression profiling in RA and ST muscles was performed on both production groups using a multi-tissue bovine cDNA repertoire. Variance analysis showed an effect of the muscle type and of the production system on gene expression (P<0.001). A list of the 212 most variable genes according to the production system was established, of which 149 genes corresponded to identified genes. They were classified according to their gene function annotation mainly in the "protein metabolism and modification", "signal transduction", "cell cycle", "developmental processes" and "muscle contraction" biological processes. Selenoprotein W was found to be underexpressed in pasture-fed animals and could be proposed as a putative gene marker of the grass-based system. In conclusion, enzyme-specific adaptations and gene expression modifications were observed in response to the production system and some of them could be candidates for grazing or grass-feeding traceability.

  18. Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects.

    PubMed

    Perez-Martinez, Pablo; Garcia-Rios, Antonio; Delgado-Lista, Javier; Gjelstad, Ingrid M F; Gibney, James; Kieć-Wilk, Beata; Camargo, Antonio; Helal, Olfa; Karlström, Brita; Blaak, Ellen E; Hall, Wendy; Risérus, Ulf; Dembińska-Kieć, Aldona; Defoort, Catherine; Saris, Wim H M; Lovegrove, Julie A; Drevon, Christian A; Roche, Helen M; Lopez-Miranda, Jose

    2013-08-01

    Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the LIPGENE cohort. The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. The broadband rotational spectrum of fully deuterated acetaldehyde (CD 3CDO) in a CW supersonic expansion

    DOE PAGES

    Zaleski, Daniel P.; Duan, Chuanxi; Carvajal, Miguel; ...

    2017-02-09

    The broadband pure rotational spectra of CD 3CDO, 13CD 3CDO, CD 3 13CDO, and CD 3CD 18O have been recorded using a BrightSpec W-Band (75–110 GHz) chirped-pulse Fourier transform millimeter wave (CP-FTmmW) spectrometer. The sample was enriched with deuterium, whereas the 13C and 18O isotopologues were observed in natural abundance (with respect to the enriched fully deuterated parent containing 12C and 16O). The analysis of the spectra is described and the derived molecular constants are compared to those of known acetaldehyde isotopologues. Furthermore, we have demonstrated the ability to record rotational spectra in a steady-state “CW” supersonic expansion with amore » duty cycle of 80%. Finally, the advantages and limitations of the segmented chirp spectrometer coupled with a CW molecular source as well as design of the vacuum and pumping system are discussed.« less

  20. The broadband rotational spectrum of fully deuterated acetaldehyde (CD 3CDO) in a CW supersonic expansion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zaleski, Daniel P.; Duan, Chuanxi; Carvajal, Miguel

    The broadband pure rotational spectra of CD 3CDO, 13CD 3CDO, CD 3 13CDO, and CD 3CD 18O have been recorded using a BrightSpec W-Band (75–110 GHz) chirped-pulse Fourier transform millimeter wave (CP-FTmmW) spectrometer. The sample was enriched with deuterium, whereas the 13C and 18O isotopologues were observed in natural abundance (with respect to the enriched fully deuterated parent containing 12C and 16O). The analysis of the spectra is described and the derived molecular constants are compared to those of known acetaldehyde isotopologues. Furthermore, we have demonstrated the ability to record rotational spectra in a steady-state “CW” supersonic expansion with amore » duty cycle of 80%. Finally, the advantages and limitations of the segmented chirp spectrometer coupled with a CW molecular source as well as design of the vacuum and pumping system are discussed.« less

  1. Biomarkers of susceptibility following benzene exposure: influence of genetic polymorphisms on benzene metabolism and health effects.

    PubMed

    Carbonari, Damiano; Chiarella, Pieranna; Mansi, Antonella; Pigini, Daniela; Iavicoli, Sergio; Tranfo, Giovanna

    2016-01-01

    Benzene is a ubiquitous occupational and environmental pollutant. Improved industrial hygiene allowed airborne concentrations close to the environmental context (1-1000 µg/m(3)). Conversely, new limits for benzene levels in urban air were set (5 µg/m(3)). The biomonitoring of exposure to such low benzene concentrations are performed measuring specific and sensitive biomarkers such as S-phenylmercapturic acid, trans, trans-muconic acid and urinary benzene: many studies referred high variability in the levels of these biomarkers, suggesting the involvement of polymorphic metabolic genes in the individual susceptibility to benzene toxicity. We reviewed the influence of metabolic polymorphisms on the biomarkers levels of benzene exposure and effect, in order to understand the real impact of benzene exposure on subjects with increased susceptibility.

  2. The influence of metabolic heat production on body temperature of a small lizard, Anolis carolinensis.

    PubMed

    Brown, Richard P; Au, Timothy

    2009-06-01

    Little is known about the impact of increased metabolism on body temperatures of small ectotherms. We found that postprandial metabolic rates of 5 g Anolis carolinensis lizards were elevated by factorial increases of 2.3+/-1.0 (mean+/-S.E.) at 26 degrees C and 3.8+/-2.1 at 30 degrees C over their fasting rates. Cloacal body temperatures exceeded environmental temperatures by a small amount in fasted individuals (26 degrees C: 0.3+/-0.02 degrees C, 30 degrees C: 0.3+/-0.02 degrees C), and by a significantly larger amount in fed individuals (26 degrees C: 1.0+/-0.06 degrees C, 30 degrees C: 0.8+/-0.08 degrees C). We conclude that an increased metabolic rate due to specific dynamic action leads to a small but significant elevation of body temperature in this species. Comparisons with thermal increments reported for a large (750 g) varanid lizard suggest that body size has only a minor influence on body-air temperature differentials of ectotherms. This is consistent with theoretical predictions. Finally, endogenous heat production could help elevate body temperatures in the wild and therefore play a minor role in thermoregulation.

  3. Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

    PubMed

    Anderson, Daniel R; Duryee, Michael J; Shurmur, Scott W; Um, John Y; Bussey, Walter D; Hunter, Carlos D; Garvin, Robert P; Sayles, Harlan R; Mikuls, Ted R; Klassen, Lynell W; Thiele, Geoffrey M

    2014-01-01

    Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

  4. Unique Antibody Responses to Malondialdehyde-Acetaldehyde (MAA)-Protein Adducts Predict Coronary Artery Disease

    PubMed Central

    Anderson, Daniel R.; Duryee, Michael J.; Shurmur, Scott W.; Um, John Y.; Bussey, Walter D.; Hunter, Carlos D.; Garvin, Robert P.; Sayles, Harlan R.; Mikuls, Ted R.; Klassen, Lynell W.; Thiele, Geoffrey M.

    2014-01-01

    Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease. PMID:25210746

  5. The influence of Dworshak Dam on epilithic community metabolism in the Clearwater River, U.S.A.

    USGS Publications Warehouse

    Munn, M.D.; Brusven, M.A.

    2004-01-01

    Epilithic community metabolism was determined on a seasonal basis over two years in nonregulated and regulated reaches of the Clearwater River in northern Idaho, U.S.A. Metabolism was estimated using three, 12-liter recirculating chambers and the dissolved oxygen method, with parameters expressed as g O2 m−2 d−1. In the nonregulated reach above the reservoir, gross community productivity (GCP) ranged from 0.8 to 3.2, community respiration (CR24) from 0.3 to 1.2, and production/respiration (P/R) ratios from 1.2 to 3.3. Epilithic metabolism in the regulated reach immediately below the dam increased sharply; GCP ranged from 4.2 to 25.5, CR24 from 1.9 to 9.7, and P/R ratios from 1.4 to 5.7. Increased primary production and respiration in the regulated reach was a result of extensive growth of an aquatic moss (Fontanalis neo-mexicanus). The influence of the dam on epilithic community metabolism was mitigated 2.5 km downstream of the dam due to the regulated North Fork of the Clearwater River (NFCR) merging with the larger, nonregulated Clearwater River. While the regulated Clearwater River below the confluence was somewhat affected by the regulated NFCR flows upstream, metabolism was similar to that found above the reservoir (GCP = 1.2 – 2.6, CR24 = 0.6 – 1.3, and P/R = 1.4 – 2.2). This study demonstrates that while Dworshak Dam has altered both primary production and respiration directly below the dam, the placement of the dam only 2.5 km upstream from a nonregulated reach greatly mitigates its effects on stream metabolism downstream.

  6. Influence of metabolism in skin on dosimetry after topical exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bronaugh, R.L.; Collier, S.W.; Macpherson, S.E.

    1994-12-01

    Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized duringmore » absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. 14 refs., 3 figs., 4 tabs.« less

  7. Influence of Iron and Aeration on Staphylococcus aureus Growth, Metabolism, and Transcription

    PubMed Central

    Ledala, Nagender; Zhang, Bo; Seravalli, Javier; Powers, Robert

    2014-01-01

    Staphylococcus aureus is a prominent nosocomial pathogen and a major cause of biomaterial-associated infections. The success of S. aureus as a pathogen is due in part to its ability to adapt to stressful environments. As an example, the transition from residing in the nares to residing in the blood or deeper tissues is accompanied by changes in the availability of nutrients and elements such as oxygen and iron. As such, nutrients, oxygen, and iron are important determinants of virulence factor synthesis in S. aureus. In addition to influencing virulence factor synthesis, oxygen and iron are critical cofactors in enzymatic and electron transfer reactions; thus, a change in iron or oxygen availability alters the bacterial metabolome. Changes in metabolism create intracellular signals that alter the activity of metabolite-responsive regulators such as CodY, RpiRc, and CcpA. To assess the extent of metabolomic changes associated with oxygen and iron limitation, S. aureus cells were cultivated in iron-limited medium and/or with decreasing aeration, and the metabolomes were examined by nuclear magnetic resonance (NMR) spectroscopy. As expected, oxygen and iron limitation dramatically decreased tricarboxylic acid (TCA) cycle activity, creating a metabolic block and significantly altering the metabolome. These changes were most prominent during post-exponential-phase growth, when TCA cycle activity was maximal. Importantly, many of the effects of iron limitation were obscured by aeration limitation. Aeration limitation not only obscured the metabolic effects of iron limitation but also overrode the transcription of iron-regulated genes. Finally, in contrast to previous speculation, we confirmed that acidification of the culture medium occurs independent of the availability of iron. PMID:24706736

  8. Malondialdehyde-acetaldehyde adducts (MAA) and anti-MAA antibody in rheumatoid arthritis

    PubMed Central

    Thiele, Geoffrey M.; Duryee, Michael J.; Anderson, Daniel R.; Klassen, Lynell W.; Mohring, Stephen M.; Young, Kathleen A.; Benissan-Messan, Dathe; Sayles, Harlan; Dusad, Anand; Hunter, Carlos D.; Sokolove, Jeremy; Robinson, William; O’Dell, James R.; Nicholas, Anthony P.; Tuma, Dean; Mikuls, Ted R.

    2017-01-01

    Objective As a product of oxidative stress associated with tolerance loss in other disease states, we investigated the presence of malondialdehyde-acetaldehyde (MAA) adducts and circulating anti-MAA antibody in rheumatoid arthritis (RA). Methods Synovial tissues from RA and osteoarthritis patients were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA cases (n = 1720) and healthy controls (n = 80) by ELISA. Antigen-specific anti-citrullinated protein antibody (ACPA) was measured in RA cases using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of cases (n = 80) and matched controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA, were examined in all RA cases. Results MAA adducts were increased in RA synovial tissues relative to osteoarthritis and co-localized with citrullinated protein. Anti-MAA antibody isotypes were increased in RA cases vs. controls (p < 0.001). Among RA cases, anti-MAA antibody isotypes were associated with ACPA and RF positivity (p < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a higher number of positive antigen-specific ACPA analytes in high titer (p < 0.001) and a higher ACPA score (p < 0.001) independent of other covariates. Conclusion MAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPA. These results support speculation that MAA formation may be a co-factor that drives tolerance loss resulting in the autoimmune responses characteristic of RA. PMID:25417811

  9. Rain influences the physiological and metabolic responses to exercise in hot conditions.

    PubMed

    Ito, Ryo; Yamashita, Naoyuki; Suzuki, Eiko; Matsumoto, Takaaki

    2015-01-01

    Outdoor exercise often proceeds in rainy conditions. However, the cooling effects of rain on human physiological responses have not been systematically studied in hot conditions. The present study determined physiological and metabolic responses using a climatic chamber that can precisely simulate hot, rainy conditions. Eleven healthy men ran on a treadmill at an intensity of 70% VO2max for 30 min in the climatic chamber at an ambient temperature of 33°C in the presence (RAIN) or absence (CON) of 30 mm · h(-1) of precipitation and a headwind equal to the running velocity of 3.15 ± 0.19 m · s(-1). Oesophageal temperature, mean skin temperature, heart rate, rating of perceived exertion, blood parameters, volume of expired air and sweat loss were measured. Oesophageal and mean skin temperatures were significantly lower from 5 to 30 min, and heart rate was significantly lower from 20 to 30 min in RAIN than in CON (P < 0.05 for all). Plasma lactate and epinephrine concentrations (30 min) and sweat loss were significantly lower (P < 0.05) in RAIN compared with CON. Rain appears to influence physiological and metabolic responses to exercise in heat such that heat-induced strain might be reduced.

  10. Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species

    PubMed Central

    Bao, Hui-Fang; Song, John Z.; Duke, Billie J.; Ma, He-Ping; Denson, Donald D.

    2012-01-01

    Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (Po) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC Po and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. PMID:22895258

  11. Conjugated linoleic acid influences the metabolism of tocopherol in lactating rats but has little effect on tissue tocopherol concentrations in pups.

    PubMed

    Zeitz, Johanna O; Most, Erika; Eder, Klaus

    2016-05-31

    Conjugated linoleic acid (CLA) is known to affect the lipid metabolism in growing and lactating animals. However, potential effects on the metabolism of fat-soluble vitamins in lactating animals and co-occurring effects on their offspring are unknown. We aimed to investigate the effects of dietary CLA on concentrations of tocopherol in various tissues of lactating rats and their offspring and expression of genes involved in tocopherol metabolism. Twenty-eight Wistar Han rats were allocated to 2 groups and fed either a control diet (control group) or a diet containing 0.9 % of cis-9, trans-11 and trans-10, cis-12 (1:1) CLA (CLA group) during pregnancy and lactation. Feed intake of dams and body weight of dams and their pups were recorded weekly. Tocopherol concentrations in various body tissues were determined at day 14 of lactation in dams and 1, 7 and 14 days after birth in pups. Expression of selected genes involved in metabolism of tocopherol was determined in dams and pups. The data were statistically analysed by analysis of variance. Feed intake and body weight development of nursing rats and their pups was similar in both groups. In livers of CLA-fed dams, tocopherol concentrations decreased by 24 % but expression of TTPA and CYP3A1, involved in tocopherol transport and metabolism, were not influenced. In the dams' adipose tissue, gene expression of receptors involved in tissue tocopherol uptake, LDLR and SCARB1, but not of LPL, increased by 30 to 50 % and tocopherol concentrations increased by 47 % in CLA-fed compared to control dams. Expression of LPL, LDLR and SCARB1 in mammary gland was not influenced by CLA-feeding. Tocopherol concentrations in the pup's livers and lungs were similar in both groups, but at 14 days of age, adipose tissue tocopherol concentrations, and LDLR and SCARB1 expression, were higher in the CLA-exposed pups. We show that dietary CLA affects tissue concentrations of tocopherol in lactating rats and tocopherol metabolism in

  12. The influence of hydrologic connectivity on ecosystem metabolism and nitrate uptake in an active beaver meadow

    NASA Astrophysics Data System (ADS)

    Wegener, P.; Covino, T. P.; Wohl, E.; Kampf, S. K.; Lacy, S.

    2015-12-01

    Wetlands have been widely demonstrated to provide important watershed services, such as the sequestration of carbon (C) and removal of nitrate (NO3-) from through-flowing water. Hydrologic connectivity (degree of water and associated material exchange) between floodplain water bodies (e.g., side channels, ponds) and the main channel influence rates of C accumulation and NO3- uptake, and the degree to which wetlands contribute to enhanced water quality at the catchment scale. However, environmental engineers have largely ignored the role of hydrologic connectivity in providing essential ecosystem services, and constructed wetlands are commonly built using compacted clay and berms that result in less groundwater and surface water exchange than observed in natural wetlands. In a study of an active beaver meadow (multithreaded, riparian wetland) in Rocky Mountain National Park, CO, we show how shifts in hydrology (connectivity, residence times, flow paths) from late spring snowmelt (high connectivity) to autumn/winter baseflow (low connectivity) influence ecosystem metabolism metrics (e.g., gross primary production, ecosystem respiration, and net ecosystem productivity) and NO3- uptake rates. We use a combination of mixing analyses, tracer tests, and hydrometric methods to evaluate shifts in surface and subsurface hydrologic connections between floodplain water bodies from snowmelt to baseflow. In the main channel and three floodplain water bodies, we quantify metabolism metrics and NO3- uptake kinetics across shifting flow regimes. Results from our research indicate that NO3- uptake and metabolism dynamics respond to changing levels of hydrologic connectivity to the main channel, emphasizing the importance of incorporating connectivity in wetland mitigation practices that seek to enhance water quality at the catchment scale.

  13. Influence of acute exercise with and without carbohydrate replacement on postprandial lipid metabolism.

    PubMed

    Harrison, Michael; O'Gorman, Donal J; McCaffrey, Noel; Hamilton, Marc T; Zderic, Theodore W; Carson, Brian P; Moyna, Niall M

    2009-03-01

    Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

  14. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis

    PubMed Central

    Zeisel, Steven H.

    2013-01-01

    There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet. In addition, farmers have recognized that the addition of a metabolite of choline (betaine) to cattle and swine feed reduces body fat/lean mass ratio. Choline dietary intake in humans varies over a >three-fold range, and genetic variation exists that modifies individual requirements for this nutrient. Although there are some epidemiologic studies in humans suggesting a link between choline/1-carbon metabolism and energy metabolism, there have been no controlled studies in humans that were specifically designed to examine this relationship. PMID:23072856

  15. SFA 2.0- Metabolic Potential

    ScienceCinema

    Banfield, Jill; Beller, Harry

    2018-05-23

    Berkeley Lab Earth Scientists Jill Banfield and Harry Beller explain the Sustainable Systems SFA 2.0 project's research on metabolic potential—or how metabolic lifestyles of microbial communities modulate in response to as well as influence environmental change.

  16. The relative influence of nutrients and habitat on stream metabolism in agricultural streams

    USGS Publications Warehouse

    Frankforter, J.D.; Weyers, H.S.; Bales, J.D.; Moran, P.W.; Calhoun, D.L.

    2010-01-01

    Stream metabolism was measured in 33 streams across a gradient of nutrient concentrations in four agricultural areas of the USA to determine the relative influence of nutrient concentrations and habitat on primary production (GPP) and respiration (CR-24). In conjunction with the stream metabolism estimates, water quality and algal biomass samples were collected, as was an assessment of habitat in the sampling reach. When data for all study areas were combined, there were no statistically significant relations between gross primary production or community respiration and any of the independent variables. However, significant regression models were developed for three study areas for GPP (r 2 = 0.79-0.91) and CR-24 (r 2 = 0.76-0.77). Various forms of nutrients (total phosphorus and area-weighted total nitrogen loading) were significant for predicting GPP in two study areas, with habitat variables important in seven significant models. Important physical variables included light availability, precipitation, basin area, and in-stream habitat cover. Both benthic and seston chlorophyll were not found to be important explanatory variables in any of the models; however, benthic ash-free dry weight was important in two models for GPP. ?? 2009 The Author(s).

  17. [Influence of valproic acid (depakine I.V.) on human placenta metabolism--experimental model].

    PubMed

    Semczuk-Sikora, Anna; Rogowska, Wanda; Semczuk, Marian

    2003-08-01

    The pregnancy in women with epilepsy is associated with an increased incidence of congenital malformations in offspring. Currently, anti-epileptic drugs (AEDs) are concerned to be a major etiologic factor of abnormal fetal development but the pathomechanism of teratogenicity of AEDs is complex and not well understood. The purpose of this study was to evaluate an influence of one of the AED-valproic acid (VPA) on placental metabolism (glucose consumption and lactate production). Term human placental cotyledons were perfused in vitro using a recycling perfusion of maternal and fetal circulations. A total 18 placentas were perfused either with 75 micrograms/ml of VPA (therapeutic dose) or with 225 micrograms/ml of VPA (toxic dose). Eight placentas were perfused with a medium without VPA and served as controls. During 2.5 h of experiment, both maternal and fetal glucose consumption and lactate production were measured every 30 minutes. The introduction of different concentrations of VPA into the perfusion system did not effect placental glucose consumption and lactate production rates in both maternal and fetal compartments. The teratogenic effect of valproic acid is not associated with metabolic disturbances of glucose or lactate in the placental tissue.

  18. Influence of gastrointestinal tract on metabolism of bisphenol A as determined by in vitro simulated system.

    PubMed

    Wang, Yonghua; Rui, Min; Nie, Yang; Lu, Guanghua

    2018-05-07

    Oral exposure is a major route of human bisphenol A (BPA) exposure. However, influence of gastrointestinal tract on BPA metabolism is unavailable. In this study, in vitro simulator of the human intestinal microbial ecosystem (SHIME) was applied to investigate the changes in bioaccessibility and metabolism of BPA in different parts of gastrointestinal tract (stomach, small intestine and colon). Then the human hepatoma cell line HepG2 was employed to compare toxic effects of BPA itself and effluents of SHIME system on hepatic gene expression profiles. Results showed that level of bioaccessible BPA decreased with the process of gastrointestinal digestion. But the gastrointestinal digestion could not completely degrade BPA. Then, BPA exposure significantly changed microbial community in colons and increased the percentage of microbes shared in ascending, transverse and descending colons. Abundances of BPA-degradable bacteria, such as Microbacterium and Alcaligenes, were up-regulated. Further, SHIME effluents significantly up-regulated expressions of genes related to estrogenic effect and oxidative stress compared to BPA itself, but reduced or had little change on the risk of cell apoptosis and fatty deposits. This study sheds new lights on influence of gastrointestinal digestion on bioaccessibility and toxic effects of BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Engineering of carboligase activity reaction in Candida glabrata for acetoin production.

    PubMed

    Li, Shubo; Xu, Nan; Liu, Liming; Chen, Jian

    2014-03-01

    Utilization of Candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. Based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (CAR) pathway and provide a direction for engineering C. glabrata. Accordingly, alcohol dehydrogenase, acetaldehyde dehydrogenase, pyruvate decarboxylase, and butanediol dehydrogenase were selected to be manipulated for strengthening the CAR pathway. Following the rational metabolic engineering, the engineered strain exhibited increased acetoin biosynthesis (2.24 g/L). In addition, through in silico simulation and redox balance analysis, NADH was identified as the key factor restricting higher acetoin production. Correspondingly, after introduction of NADH oxidase, the final acetoin production was further increased to 7.33 g/L. By combining the rational metabolic engineering and cofactor engineering, the acetoin-producing C. glabrata was improved stepwise, opening a novel pathway for rational development of microorganisms for bioproduction. Copyright © 2013. Published by Elsevier Inc.

  20. Reactive Oxygen Species in Metabolic and Inflammatory Signaling.

    PubMed

    Forrester, Steven J; Kikuchi, Daniel S; Hernandes, Marina S; Xu, Qian; Griendling, Kathy K

    2018-03-16

    Reactive oxygen species (ROS) are well known for their role in mediating both physiological and pathophysiological signal transduction. Enzymes and subcellular compartments that typically produce ROS are associated with metabolic regulation, and diseases associated with metabolic dysfunction may be influenced by changes in redox balance. In this review, we summarize the current literature surrounding ROS and their role in metabolic and inflammatory regulation, focusing on ROS signal transduction and its relationship to disease progression. In particular, we examine ROS production in compartments such as the cytoplasm, mitochondria, peroxisome, and endoplasmic reticulum and discuss how ROS influence metabolic processes such as proteasome function, autophagy, and general inflammatory signaling. We also summarize and highlight the role of ROS in the regulation metabolic/inflammatory diseases including atherosclerosis, diabetes mellitus, and stroke. In order to develop therapies that target oxidative signaling, it is vital to understand the balance ROS signaling plays in both physiology and pathophysiology, and how manipulation of this balance and the identity of the ROS may influence cellular and tissue homeostasis. An increased understanding of specific sources of ROS production and an appreciation for how ROS influence cellular metabolism may help guide us in the effort to treat cardiovascular diseases. © 2018 American Heart Association, Inc.

  1. Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

    PubMed Central

    Robey, R.Brooks; Weisz, Judith; Kuemmerle, Nancy; Salzberg, Anna C.; Berg, Arthur; Brown, Dustin G.; Kubik, Laura; Palorini, Roberta; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Colacci, Annamaria; Mondello, Chiara; Raju, Jayadev; Woodrick, Jordan; Scovassi, A.Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Hamid, Roslida A.; Williams, Graeme P.; Lowe, Leroy; Meyer, Joel; Martin, Francis L.; Bisson, William H.; Chiaradonna, Ferdinando; Ryan, Elizabeth P.

    2015-01-01

    Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the

  2. Consequences of complex environments: Temperature and energy intake interact to influence growth and metabolic rate.

    PubMed

    Stahlschmidt, Zachary R; Jodrey, Alicia D; Luoma, Rachel L

    2015-09-01

    The field of comparative physiology has a rich history of elegantly examining the effects of individual environmental factors on performance traits linked to fitness (e.g., thermal performance curves for locomotion). However, animals live in complex environments wherein multiple environmental factors co-vary. Thus, we investigated the independent and interactive effects of temperature and energy intake on the growth and metabolic rate of juvenile corn snakes (Pantherophis guttatus) in the context of shifts in complex environments. Unlike previous studies that imposed constant or fluctuating temperature regimes, we manipulated the availability of preferred thermal microclimates (control vs. relatively warm regimes) for eight weeks and allowed snakes to behaviorally thermoregulate among microclimates. By also controlling for energy intake, we demonstrate an interactive effect of temperature and energy on growth-relevant temperature shifts had no effect on snakes' growth when energy intake was low and a positive effect on growth when energy intake was high. Thus, acclimation to relatively warm thermal options can result in increased rates of growth when food is abundant in a taxon in which body size confers fitness advantages. Temperature and energy also interactively influenced metabolic rate-snakes in the warmer temperature regime exhibited reduced metabolic rate (O2 consumption rate at 25 °C and 30 °C) if they had relatively high energy intake. Although we advocate for continued investigation into the effects of complex environments on other traits, our results indicate that warming may actually benefit important life history traits in some taxa and that metabolic shifts may underlie thermal acclimation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

    PubMed

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Solivera, Juan; Garcia-Rios, Antonio; Perez-Caballero, A I; Lovegrove, Julie A; Drevon, Christian A; Defoort, Catherine; Blaak, Ellen E; Dembinska-Kieć, Aldona; Risérus, Ulf; Herruzo-Gomez, Ezequiel; Camargo, Antonio; Ordovas, Jose M; Roche, Helen; Lopez-Miranda, José

    2014-02-01

    Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

  4. Vitamin B1-catalyzed acetoin formation from acetaldehyde: a key step for upgrading bioethanol to bulk C₄ chemicals.

    PubMed

    Lu, Ting; Li, Xiukai; Gu, Liuqun; Zhang, Yugen

    2014-09-01

    The production of bulk chemicals and fuels from renewable biobased feedstocks is of significant importance for the sustainability of human society. The production of ethanol from biomass has dramatically increased and bioethanol also holds considerable potential as a versatile building block for the chemical industry. Herein, we report a highly selective process for the conversion of ethanol to C4 bulk chemicals, such as 2,3-butanediol and butene, via a vitamin B1 (thiamine)-derived N-heterocyclic carbene (NHC)-catalyzed acetoin condensation as the key step to assemble two C2 acetaldehydes into a C4 product. The environmentally benign and cheap natural catalyst vitamin B1 demonstrates high selectivity (99%), high efficiency (97% yield), and high tolerance toward ethanol and water impurities in the acetoin reaction. The results enable a novel and efficient process for ethanol upgrading. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy

    PubMed Central

    Brandt, Moritz; Garlapati, Venkata; Oelze, Matthias; Sotiriou, Efthymios; Knorr, Maike; Kröller-Schön, Swenja; Kossmann, Sabine; Schönfelder, Tanja; Morawietz, Henning; Schulz, Eberhard; Schultheiss, Heinz-Peter; Daiber, Andreas; Münzel, Thomas; Wenzel, Philip

    2016-01-01

    Alcoholic cardiomyopathy (ACM) resulting from excess alcohol consumption is an important cause of heart failure (HF). Although it is assumed that the cardiotoxicity of the ethanol (EtOH)-metabolite acetaldehyde (ACA) is central for its development and progression, the exact mechanisms remain obscure. Murine cardiomyocytes (CMs) exposed to ACA or EtOH showed increased superoxide (O2•−) levels and decreased mitochondrial polarization, both being normalized by NADPH oxidase (NOX) inhibition. C57BL/6 mice and mice deficient for the ACA-degrading enzyme mitochondrial aldehyde dehydrogenase (ALDH-2−/−) were fed a 2% EtOH diet for 5 weeks creating an ACA-overload. 2% EtOH-fed ALDH-2−/− mice exhibited a decreased cardiac function, increased heart-to-body and lung-to-body weight ratios, increased cardiac levels of the lipid peroxidation product malondialdehyde (MDA) as well as increased NOX activity and NOX2/glycoprotein 91phox (NOX2/gp91phox) subunit expression compared to 2% EtOH-fed C57BL/6 mice. Echocardiography revealed that ALDH-2−/−/gp91phox−/− mice were protected from ACA-overload-induced HF after 5 weeks of 2% EtOH-diet, demonstrating that NOX2-derived O2•− contributes to the development of ACM. Translated to human pathophysiology, we found increased gp91phox expression in endomyocardial biopsies of ACM patients. In conclusion, ACM is promoted by ACA-driven mitochondrial dysfunction and can be improved by ablation of NOX2/gp91phox. NOX2/gp91phox therefore might be a potential pharmacological target to treat ACM. PMID:27624556

  6. [Metabolic safety of antidepressant medicines].

    PubMed

    Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

    2017-05-23

    Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

  7. Discharge modulates stream metabolism dependence on fine particulate organic carbon in a Mediterranean WWTP-influenced stream

    NASA Astrophysics Data System (ADS)

    Drummond, J. D.; Bernal, S.; Meredith, W.; Schumer, R.; Martí Roca, E.

    2017-12-01

    Waste water treatment plant (WWTP) effluents constitute point source inputs of fine sediment, nutrients, carbon, and microbes to stream ecosystems. A range of responses to these inputs may be observed in recipient streams, including increases in respiration rates, which augment CO2 emissions to the atmosphere. Yet, little is known about which fractions of organic carbon (OC) contribute the most to stream metabolism in WWTP-influenced streams. Fine particulate OC (POC) represents ca. 40% of the total mass of OC in river networks, and is generally more labile than dissolved OC. Therefore, POC inputs from WWTPs could contribute disproportionately to higher rates of heterotrophic metabolism by stream microbial communities. The aim of this study was to investigate the influence of POC inputs from a WWTP effluent on the metabolism of a Mediterranean stream over a wide range of hydrologic conditions. We hypothesized that POC inputs would have a positive effect on respiration rates, and that the response to POC availability would be larger during low flows when the dilution capacity of the recipient stream is negligible. We focused on the easily resuspended fine sediment near the sediment-water interface (top 3 cm), as this region is a known hot spot for biogeochemical processes. For one year, samples of resuspended sediment were collected bimonthly at 7 sites from 0 to 800 m downstream of the WWTP point source. We measured total POC, organic matter (OM) content (%), and the associated metabolic activity of the resuspended sediment using the resazurin-resorufin smart tracer system as a proxy for aerobic ecosystem respiration. Resuspended sediment showed no difference in total POC over the year, while the OM content increased with decreasing discharge. This result together with the decreasing trend of total POC observed downstream of the point source during autumn after a long dry period, suggests that the WWTP effluent was the main contributor to stream POC. Furthermore

  8. Mycobacterium tuberculosis Metabolism

    PubMed Central

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  9. Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.

    PubMed

    Durgan, David J; Moore, Michael W S; Ha, Ngan P; Egbejimi, Oluwaseun; Fields, Anna; Mbawuike, Uchenna; Egbejimi, Anu; Shaw, Chad A; Bray, Molly S; Nannegari, Vijayalakshmi; Hickson-Bick, Diane L; Heird, William C; Dyck, Jason R B; Chandler, Margaret P; Young, Martin E

    2007-10-01

    Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

  10. Influence of Niche-Specific Nutrients on Secondary Metabolism in Vibrionaceae.

    PubMed

    Giubergia, Sonia; Phippen, Christopher; Gotfredsen, Charlotte H; Nielsen, Kristian Fog; Gram, Lone

    2016-07-01

    Many factors, such as the substrate and the growth phase, influence biosynthesis of secondary metabolites in microorganisms. Therefore, it is crucial to consider these factors when establishing a bioprospecting strategy. Mimicking the conditions of the natural environment has been suggested as a means of inducing or influencing microbial secondary metabolite production. The purpose of the present study was to determine how the bioactivity of Vibrionaceae was influenced by carbon sources typical of their natural environment. We determined how mannose and chitin, compared to glucose, influenced the antibacterial activity of a collection of Vibrionaceae strains isolated because of their ability to produce antibacterial compounds but that in subsequent screenings seemed to have lost this ability. The numbers of bioactive isolates were 2- and 3.5-fold higher when strains were grown on mannose and chitin, respectively, than on glucose. As secondary metabolites are typically produced during late growth, potential producers were also allowed 1 to 2 days of growth before exposure to the pathogen. This strategy led to a 3-fold increase in the number of bioactive strains on glucose and an 8-fold increase on both chitin and mannose. We selected two bioactive strains belonging to species for which antibacterial activity had not previously been identified. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry and bioassay-guided fractionation, we found that the siderophore fluvibactin was responsible for the antibacterial activity of Vibrio furnissii and Vibrio fluvialis These results suggest a role of chitin in the regulation of secondary metabolism in vibrios and demonstrate that considering bacterial ecophysiology during development of screening strategies will facilitate bioprospecting. A challenge in microbial natural product discovery is the elicitation of the biosynthetic gene clusters that are silent when microorganisms are grown under

  11. Influence of experimental hyperthyroidism on skeletal muscle metabolism in the rat.

    PubMed

    van Hardeveld, C; Kassenaar, A A

    1977-05-01

    In this study hind-limb perfusion was used to investigate the influence of thyroid hormones on some metabolic parameters in the skeletal muscle of the rat. Daily injection of 20 microng L-thyroxine (T4) per 100 g b. w. for a week caused a 25% increase in oxygen consumption. Further enlargement of the T4 dose had little additive effect. In the dose range 20--80 microng T4/100g b.w., no important changes occurred in lactate production or glucose consumption. Only at the highest T4 dose did the glucose consumption increase significantly. The most profound effect of T4 was on lipolysis. A daily dose of 20 microng T4/100 g b. w. gave a doubling of glycerol production rate, the maximum occuring at a dose of 40 microng T4/100 g b. w. Inactivation of the nervous system was without influence on the T4-induced increase in oxygen consumption. However, the T4-induced elevation of lipolysis disappeared after abolition of the nervous activity. This raises the possibility that the T4 effect on lipolysis in skeletal muscle is a potentiation of catecholamine effects. The T4-induced oxygen consumption increase might be dependent not on the lipolytic process but rather on other energy-consuming cell processes.

  12. Olfaction Under Metabolic Influences

    PubMed Central

    2012-01-01

    Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis. PMID:22832483

  13. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

    PubMed

    Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

  14. Hypertriglyceridemia Influences the Degree of Postprandial Lipemic Response in Patients with Metabolic Syndrome and Coronary Artery Disease: From the Cordioprev Study

    PubMed Central

    Alcala-Diaz, Juan F.; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Marin, Carmen; Quintana-Navarro, Gracia M.; Gomez-Luna, Purificacion; Camargo, Antonio; Almaden, Yolanda; Caballero, Javier; Tinahones, Francisco J.; Ordovas, Jose M.

    2014-01-01

    Objective To determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria. Materials and Methods 1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state Results Postprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (p<0.001), area under the curve of triglycerides (p<0.001) and incremental area under the curve of triglycerides (p<0.001). However, the influence of them on postprandial triglycerides remained statistically significant only in those patients without basal hypertriglyceridemia. Interestingly, in stepwise multiple linear regression analysis with the AUC of triglycerides as the dependent variable, only fasting triglycerides, fasting glucose and waist circumference appeared as significant independent (P<0.05) contributors. The multiple lineal regression (R) was 0.77, and fasting triglycerides showed the greatest effect on AUC of triglycerides with a standardized coefficient of 0.75. Conclusions Fasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. PMID:24802225

  15. Production of Reactive Oxygen Species by Polyhalogenated Cyclic Hydrocarbons (PCH)

    DTIC Science & Technology

    1991-07-22

    dry ice in metabolism cages. One ml aliquots of urine were derivatized with 2,4- dinitrophenylhydrazine , and extracted with pentane. The hydrazones of...U.S.A. Key Words: formaldehyde; acetaldehyde; malondialdehyde; acetone; high pressure liquid chromatography; 2,4- dinitrophenylhydrazine ; gas... dinitrophenylhydrazine , and extracted with pentane. The hydrazones of the four lipid metabolic products were quantitated by high pressure liquid chromatography

  16. Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats.

    PubMed

    Florek, Ewa; Kulza, Maksymilian; Piekoszewski, Wojciech; Gomółka, Ewa; Jawień, Wojciech; Teżyk, Artur; Napierała, Marta

    2015-10-01

    A vast majority of people who abuse alcohol are also defined as "heavy smokers". Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use of both of them. The aim of the study was to evaluate the influence of tobacco smoke xenobiotics on ethanol pharmacokinetics and the level of its metabolites in alcohol preferring and non-preferring rats. Ethanol, acetaldehyde, methanol, n-propanol and n-butanol were determined in whole blood by means of gas chromatography. Cotinine in serum was determined by LC-MS/MS. A non-compartmental analysis (cotinine, acetaldehyde) and Widmark equation (ethanol) were used for pharmacokinetic parameters calculation. Ethanol levels were lower in animals exposed to tobacco smoke compared to rats receiving this xenobiotic, without a prior exposure to tobacco smoke. Lower values of the studied pharmacokinetic parameters were observed in the alcohol preferring males compared to the non-alcohol preferring rats. Both n-propanol and n-butanol had higher values of the pharmacokinetic parameters analyzed in the animals exposed to tobacco smoke and ethanol compared to those, which ethanol was administered only once. An increase in maximum concentration and the area under concentration-time curve for ethanol after its administration to rats preferring alcohol and exposed to tobacco smoke are accompanied by a decrease in the volume of distribution. The changes in the volume of distribution may be caused by an increase in the first-pass effect, in the intestinal tract and/or in the liver. The acetaldehyde elimination rate constant was significantly higher in alcohol-preferring animals. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. Influence of metabolic-linked early life factors on the eruption timing of the first primary tooth.

    PubMed

    Un Lam, Carolina; Hsu, Chin-Ying Stephen; Yee, Robert; Koh, David; Lee, Yung Seng; Chong, Mary Foong-Fong; Cai, Meijin; Kwek, Kenneth; Saw, Seang Mei; Godfrey, Keith; Gluckman, Peter; Chong, Yap Seng

    2016-11-01

    Early eruption of permanent teeth has been associated with childhood obesity and diabetes mellitus, suggesting links between tooth eruption and metabolic conditions. This longitudinal study aimed to identify pre-, peri- and postnatal factors with metabolic consequences during infancy that may affect the eruption timing of the first primary tooth (ETFT) in children from an ethnically heterogeneous population residing within the same community. Participants were recruited (n = 1033) through the GUSTO (Growing Up in Singapore Towards healthy Outcomes) birth cohort (n = 1237). Oral examinations were performed at 3-month intervals from 6 to 18 months of age. Crude and adjusted analyses, with generalized linear modelling, were conducted to link ETFT to potential determinants occurring during pregnancy, delivery/birth and early infancy. Overall mean eruption age of the first primary tooth was 8.5 (SD 2.6) months. Earlier tooth eruption was significantly associated with infant's rate of weight gain during the first 3 months of life and increased maternal childbearing age. Compared to their Chinese counterparts, Malay and Indian children experienced significantly delayed tooth eruption by 1.2 and 1.7 months, respectively. Infant weight gain from birth to 3 months, ethnicity and maternal childbearing age were significant determinants of first tooth eruption timing. Early life influences can affect primary tooth development, possibly via metabolic pathways. Timing of tooth eruption is linked to general growth and metabolic function. Therefore, it has potential in forecasting oral and systemic conditions such as caries and obesity.

  18. Density functional theory study of acetaldehyde hydrodeoxygenation on MoO3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mei, Donghai; Karim, Ayman M.; Wang, Yong

    2011-04-06

    Periodic spin-polarized density functional theory calculations were performed to investigate acetaldehyde (CH3CHO) hydrodeoxygenation on the reduced molybdenum trioxide (MoO3) surface. The perfect O-terminated α-MoO3(010) surface is reduced to generate an oxygen defect site in the presence of H2. H2 dissociatively adsorbs at the surface oxygen sites forming two surface hydroxyls, which can recombine into a water molecule weakly bound at the Mo site. A terminal oxygen (Ot) defect site thus forms after water desorption. CH3CHO adsorbs at the O-deficient Mo site via either the sole O-Mo bond or the O-Mo and the C-O double bonds. The possible reaction pathways ofmore » the adsorbed CH3CHO with these two configurations were thoroughly examined using the dimer searching method. Our results show that the ideal deoxygenation of CH3CHO leading to ethylene (C2H4) on the reduced MoO3(010) surface is feasible. The adsorbed CH3CHO first dehydrogenate into CH2CHO by reacting with a neighboring terminal Ot. The hydroxyl (OtH) then hydrogenates CH2CHO into CH2CH2O to complete the hydrogen transfer cycle with an activation barrier of 1.39 eV. The direct hydrogen transfer from CH3CHO to CH2CH2O is unlikely due to the high barrier of 2.00 eV. The produced CH2CH2O readily decomposes into C2H4 that directly releases to the gas phase, and regenerates the Ot atom on the Mo site. As a result, the reduced MoO3(010) surface is reoxidized to the perfect MoO3(010) surface after CH3CHO deoxygenation. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.« less

  19. Signaling Pathways Regulating Redox Balance in Cancer Metabolism

    PubMed Central

    De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

    2018-01-01

    The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells’ demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions. PMID:29740540

  20. Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

    PubMed

    De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

    2018-01-01

    The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

  1. The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

    NASA Technical Reports Server (NTRS)

    Obenland, D. M.; Brown, C. S.

    1994-01-01

    We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.

  2. ALDH1B1 links alcohol consumption and diabetes.

    PubMed

    Singh, Surendra; Chen, Ying; Matsumoto, Akiko; Orlicky, David J; Dong, Hongbin; Thompson, David C; Vasiliou, Vasilis

    2015-08-07

    Aldehyde dehydrogenase 1B1 (ALDH1B1) is a mitochondrial enzyme sharing 65% and 72% sequence identity with ALDH1A1 and ALDH2 proteins, respectively. Compared to the latter two ALDH isozymes, little is known about the physiological functions of ALDH1B1. Studies in humans indicate that ALDH1B1 may be associated with alcohol sensitivity and stem cells. Our recent in vitro studies using human ALDH1B1 showed that it metabolizes acetaldehyde and retinaldehyde. To investigate the in vivo role of ALDH1B1, we generated and characterized a global Aldh1b1 knockout mouse line. These knockout (KO) mice are fertile and show overtly good health. However, ethanol pharmacokinetic analysis revealed ∼40% increase in blood acetaldehyde levels in KO mice. Interestingly, the KO mice exhibited higher fasting blood glucose levels. Collectively, we show for the first time the functional in vivo role of ALDH1B1 in acetaldehyde metabolism and in maintaining glucose homeostasis. This mouse model is a valuable tool to investigate the mechanism by which alcohol may promote the development of diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  4. Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes.

    PubMed

    Teixeira, Tatiana F S; Alves, Raquel D M; Moreira, Ana Paula B; Peluzio, Maria do Carmo G

    2015-03-01

    In this review, the influence of fat depots on insulin resistance and the main characteristics of metabolically obese normal-weight and metabolically healthy obese phenotypes are discussed. Medline/PubMed and Science Direct were searched for articles related to the terms metabolically healthy obesity, metabolically obese normal weight, adipose tissue, and insulin resistance. Normal weight and obesity might be heterogeneous in regard to their effects. Fat distribution and lower insulin sensitivity are the main factors defining phenotypes within the same body mass index. Although these terms are interesting, controversies about them remain. Future studies exploring these phenotypes will help elucidate the roles of adiposity and/or insulin resistance in the development of metabolic alterations. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. [Psychopharmacology and metabolic syndrome].

    PubMed

    Telles-Correia, Diogo; Guerreiro, Diogo F; Coentre, Ricardo; Coentre, Rui; Góis, C; Figueira, Luísa

    2008-01-01

    Metabolic Syndrome consists in a group of metabolic changes, being the most important problem insulin resistence. Other important components of this syndrome are abdominal obesity, hypertension and hyperlipidemia /hypercholestrolemia. It was demonstrated that psychiatric patients have a greater risk to develop metabolic syndrome with a prevalence of 41%. Prevalence of this syndrome in psychiatric male patients is 138% higher than in general population and in female patients 251% higher. Some of the factors that can explain this increase of metabolic risk in psychiatric patients are psychiatric drugs. We preformed a systematic review of literature published until June, 2007, by means of MEDLINE. Studies reviewed include clinical cases, reviews, analytic and observational studies. We selected 72 articles. Authors pretend to understand the mechanisms, by which, different psychiatric drugs can influence metabolic syndrome, and strategies for prevention of this situation.

  6. Influence of Wastewater Discharge on the Metabolic Potential of the Microbial Community in River Sediments.

    PubMed

    Li, Dong; Sharp, Jonathan O; Drewes, Jörg E

    2016-01-01

    To reveal the variation of microbial community functions during water filtration process in river sediments, which has been utilized widely in natural water treatment systems, this study investigates the influence of municipal wastewater discharge to streams on the phylotype and metabolic potential of the microbiome in upstream and particularly various depths of downstream river sediments. Cluster analyses based on both microbial phylogenetic and functional data collectively revealed that shallow upstream sediments grouped with those from deeper subsurface downstream regions. These sediment samples were distinct from those found in shallow downstream sediments. Functional genes associated with carbohydrate, xenobiotic, and certain amino acid metabolisms were overrepresented in upstream and deep downstream samples. In contrast, the more immediate contact with wastewater discharge in shallow downstream samples resulted in an increase in the relative abundance of genes associated with nitrogen, sulfur, purine and pyrimidine metabolisms, as well as restriction-modification systems. More diverse bacterial phyla were associated with upstream and deep downstream sediments, mainly including Actinobacteria, Planctomycetes, and Firmicutes. In contrast, in shallow downstream sediments, genera affiliated with Betaproteobacteria and Gammaproteobacteria were enriched with putative functions that included ammonia and sulfur oxidation, polyphosphate accumulation, and methylotrophic bacteria. Collectively, these results highlight the enhanced capabilities of microbial communities residing in deeper stream sediments for the transformation of water contaminants and thus provide a foundation for better design of natural water treatment systems to further improve the removal of contaminants.

  7. Rewiring and regulation of cross-compartmentalized metabolism in protists

    PubMed Central

    Ginger, Michael L.; McFadden, Geoffrey I.; Michels, Paul A. M.

    2010-01-01

    Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation. PMID:20124348

  8. Thyroid hormone metabolism and environmental chemical exposure

    PubMed Central

    2012-01-01

    Background Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism. Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. Methods Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB

  9. Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

    PubMed

    Bu, Pengcheng; Chen, Kai-Yuan; Xiang, Kun; Johnson, Christelle; Crown, Scott B; Rakhilin, Nikolai; Ai, Yiwei; Wang, Lihua; Xi, Rui; Astapova, Inna; Han, Yan; Li, Jiahe; Barth, Bradley B; Lu, Min; Gao, Ziyang; Mines, Robert; Zhang, Liwen; Herman, Mark; Hsu, David; Zhang, Guo-Fang; Shen, Xiling

    2018-06-05

    Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Psychiatrists' follow-up of identified metabolic risk: a mixed-method analysis of outcomes and influences on practice.

    PubMed

    Patterson, Sue; Freshwater, Kathleen; Goulter, Nicole; Ewing, Julie; Leamon, Boyd; Choudhary, Anand; Moudgil, Vikas; Emmerson, Brett

    2016-10-01

    Aims and method To describe and explain psychiatrists' responses to metabolic abnormalities identified during screening. We carried out an audit of clinical records to assess rates of monitoring and follow-up practice. Semi-structured interviews with 36 psychiatrists followed by descriptive and thematic analyses were conducted. Results Metabolic abnormalities were identified in 76% of eligible patients screened. Follow-up, recorded for 59%, was variable but more likely with four or more abnormalities. Psychiatrists endorse guidelines but ambivalence about responsibility, professional norms, resource constraints and skills deficits as well as patient factors influences practice. Therapeutic optimism and desire to be a 'good doctor' supported comprehensive follow-up. Clinical implications Psychiatrists are willing to attend to physical healthcare, and obstacles to recommended practice are surmountable. Psychiatrists seek consensus among stakeholders about responsibilities and a systemic approach addressing the social determinants of health inequities. Understanding patients' expectations is critical to promoting best practice.

  11. Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats.

    EPA Science Inventory

    SOT2014 Abstract for presentation: March 23-27, 2014; Phoenix, AZ Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats. V. Bass, D. Andrews, J. Richards, M. Schladweiler, A. Ledb...

  12. A Hyporheic Mesocosm Experiment: Influence of Quantity and Quality of stream-source DOC on Rates of Hyporheic Metabolism

    NASA Astrophysics Data System (ADS)

    Serchan, S. P.; Wondzell, S. M.; Haggerty, R.; Pennington, R.; Feris, K. P.; Sanfilippo, A. R.; Reeder, W. J.; Tonina, D.

    2016-12-01

    Hyporheic zone biogeochemical processes can influence stream water chemistry. Some estimates show that 50-90% stream water CO2 is produced in the hyporheic zone through heterotrophic metabolism of organic matter, usually supplied from the stream as dissolved organic carbon (DOC). Preliminary results from our well network at the HJ Andrews WS1, indicate that dissolved inorganic carbon (DIC) is 1.5-2 times higher in the hyporheic zone than in stream water. Conversely, DOC (mg/L) is 1.5 times higher in stream water than in the hyporheic zone throughout the year. Overall, the hyporheic zone appears to be a net source of DIC. However, the increase in DIC along hyporheic flow paths is approximately 10-times greater than the loss of DOC, suggesting that metabolism of buried particulate organic carbon (POC) is a major source of organic carbon for microbial metabolism. However, we cannot completely rule out alternative sources of DIC, especially those originating in the overlying riparian soil, because hyporheic processes are difficult to isolate in well networks. To study hyporheic zone biogeochemical processes, particularly the transformation of organic carbon to inorganic carbon species, we designed and built six replicate 2-m long hyporheic mesocosms in which we are conducting DOC amendment experiments. We examine the role of DOC quality and quantity on hyporheic respiration by injecting labile (acetate) and refractory (fulvic acid) organic carbon and comparing rates of O2 consumption, DOC loss, and DIC gains against a control. We expect that stream source DOC is limiting in this small headwater stream, forcing hyporheic metabolism to rely on buried POC. However, the long burial time of POC suggests it is likely of low quality so that supplying labile DOC in stream water should shift hyporheic metabolism away from POC rather than increase the overall rate of metabolism. Future experiments will examine natural sources of DOC (stream periphyton, leaf, and soil humic

  13. Tumor Macroenvironment and Metabolism

    PubMed Central

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%–20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient’s outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. PMID:24787299

  14. Tumor macroenvironment and metabolism.

    PubMed

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Influence of closure, phenolic levels and microoxygenation on Cabernet Sauvignon wine composition after 5 years' bottle storage.

    PubMed

    Han, Guomin; Ugliano, Maurizio; Currie, Bruce; Vidal, Stéphane; Diéval, Jean-Baptiste; Waterhouse, Andrew L

    2015-01-01

    Wine aging is generally limited by the amount of oxidation, which is dependent on the amount of oxygen entering via the closure. Cabernet Sauvignon wine is well known for its high concentration of tannin, making it an ideal red wine for aging. The impact of closure type after 5 years' bottle aging has been investigated on a 2007 Cabernet Sauvignon red wine, treated with or without polyvinylpolypyrrolidone (PVPP) and micro-oxygenation (Mox). Two oxygen transfer rate (OTR) conditions (16 and 5 µg per day) into 375 mL bottles were obtained by using different synthetic stoppers. Color was evaluated by UV-visible spectrophotometry, carbonyls by 2,4-dinitrophenylhydrazine derivatization, phenolics by high-performance liquid chromatography and sulfur dioxide by the aspiration method. Closure type strongly influenced color parameters involving SO2 bleaching and some phenolics, particularly quercetin, were affected, but there was little effect on carbonyls other than acetaldehyde. PVPP treatment afforded wines with the lowest levels of phenolics and color density, but highest acetaldehyde. Few effects of Mox could be detected. Closure OTR strongly affects sulfur dioxide levels - the primary antioxidant in wine - in aged wine, but phenolic levels substantially alter the secondary reactions of oxidative aging. © 2014 Society of Chemical Industry.

  16. Acid base properties of cyanobacterial surfaces I: Influences of growth phase and nitrogen metabolism on cell surface reactivity

    NASA Astrophysics Data System (ADS)

    Lalonde, S. V.; Smith, D. S.; Owttrim, G. W.; Konhauser, K. O.

    2008-03-01

    Significant efforts have been made to elucidate the chemical properties of bacterial surfaces for the purposes of refining surface complexation models that can account for their metal sorptive behavior under diverse conditions. However, the influence of culturing conditions on surface chemical parameters that are modeled from the potentiometric titration of bacterial surfaces has received little regard. While culture age and metabolic pathway have been considered as factors potentially influencing cell surface reactivity, statistical treatments have been incomplete and variability has remained unconfirmed. In this study, we employ potentiometric titrations to evaluate variations in bacterial surface ligand distributions using live cells of the sheathless cyanobacterium Anabaena sp. strain PCC 7120, grown under a variety of batch culture conditions. We evaluate the ability for a single set of modeled parameters, describing acid-base surface properties averaged over all culture conditions tested, to accurately account for the ligand distributions modeled for each individual culture condition. In addition to considering growth phase, we assess the role of the various assimilatory nitrogen metabolisms available to this organism as potential determinants of surface reactivity. We observe statistically significant variability in site distribution between the majority of conditions assessed. By employing post hoc Tukey-Kramer analysis for all possible pair-wise condition comparisons, we conclude that the average parameters are inadequate for the accurate chemical description of this cyanobacterial surface. It was determined that for this Gram-negative bacterium in batch culture, ligand distributions were influenced to a greater extent by nitrogen assimilation pathway than by growth phase.

  17. Hypoxia, gas narcosis, and metabolic response to argon and nitrous oxide

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Studies of the mechanism of inert gas influence on metabolism are reported. The studies reported include: metabolic response of hamsters to argon and nitrous oxide, membrane fatty acids and susceptability to narcotic gas influence, narcosis-induced histotoxic hypoxia, biochemical study of inert gas narcosis, hypoxia-induced protection against cardiovascular deterioration in the weightless state, and acute metabolic and physiologic response of goats to narcosis.

  18. Microclimate influence on mineral and metabolic profiles of grape berries.

    PubMed

    Pereira, G E; Gaudillere, J-P; Pieri, P; Hilbert, G; Maucourt, M; Deborde, C; Moing, A; Rolin, D

    2006-09-06

    The grape berry microclimate is known to influence berry quality. The effects of the light exposure of grape berry clusters on the composition of berry tissues were studied on the "Merlot" variety grown in a vineyard in Bordeaux, France. The light exposure of the fruiting zone was modified using different intensities of leaf removal, cluster position relative to azimuth, and berry position in the cluster. Light exposures were identified and classified by in situ measurements of berry temperatures. Berries were sampled at maturity (>19 Brix) for determination of skin and/or pulp chemical and metabolic profiles based on (1) chemical and physicochemical measurement of minerals (N, P, K, Ca, Mg), (2) untargeted 1H NMR metabolic fingerprints, and HPLC targeted analyses of (3) amino acids and (4) phenolics. Each profile defined by partial least-square discriminant analysis allowed us to discriminate berries from different light exposure. Discriminant compounds between shaded and light-exposed berries were quercetin-3-glucoside, kaempferol-3-glucoside, myricetin-3-glucoside, and isorhamnetin-3-glucoside for the phenolics, histidine, valine, GABA, alanine, and arginine for the amino acids, and malate for the organic acids. Capacities of the different profiling techniques to discriminate berries were compared. Although the proportion of explained variance from the 1H NMR fingerprint was lower compared to that of chemical measurements, NMR spectroscopy allowed us to identify lit and shaded berries. Light exposure of berries increased the skin and pulp flavonols, histidine and valine contents, and reduced the organic acids, GABA, and alanine contents. All the targeted and nontargeted analytical data sets used made it possible to discriminate sun-exposed and shaded berries. The skin phenolics pattern was the most discriminating and allowed us to sort sun from shade berries. These metabolite classes can be used to qualify berries collected in an undetermined environment. The

  19. The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

    PubMed Central

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

  20. Sublethal Concentrations of Antibiotics Cause Shift to Anaerobic Metabolism in Listeria monocytogenes and Induce Phenotypes Linked to Antibiotic Tolerance

    PubMed Central

    Knudsen, Gitte M.; Fromberg, Arvid; Ng, Yin; Gram, Lone

    2016-01-01

    The human pathogenic bacterium Listeria monocytogenes is exposed to antibiotics both during clinical treatment and in its saprophytic lifestyle. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and induce antibiotic tolerance. Transcriptomic analyses demonstrated that each of the four antibiotics tested caused an antibiotic-specific gene expression pattern related to mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism and higher ethanol production. A mutant in the bifunctional acetaldehyde-CoA/alcohol dehydrogenase encoded by lmo1634 did not have altered antibiotic tolerance. However, a mutant in lmo1179 (eutE) encoding an aldehyde oxidoreductase where rerouting caused increased ethanol production was tolerant to three of four antibiotics tested. This shift in metabolism could be a survival strategy in response to antibiotics to avoid generation of ROS production from respiration by oxidation of NADH through ethanol production. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin, and this correlated with an observed antibiotic-dependent biofilm formation. A monocin mutant (ΔlmaDCBA) had increased biofilm formation when exposed to increasing concentration of co-trimoxazole similar to the wild type, but was more tolerant to killing by co-trimoxazole and ampicillin. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal antibiotic concentrations. PMID:27462313

  1. Influence of nanophase titania topography on bacterial attachment and metabolism

    PubMed Central

    Park, Margaret R; Banks, Michelle K; Applegate, Bruce; Webster, Thomas J

    2008-01-01

    Surfaces with nanophase compared to conventional (or nanometer smooth) topographies are known to have different properties of area, charge, and reactivity. Previously published research indicates that the attachment of certain bacteria (such as Pseudomonas fluorescens 5RL) is higher on surfaces with nanophase compared to conventional topographies, however, their effect on bacterial metabolism is unclear. Results presented here show that the adhesion of Pseudomonas fluorescens 5RL and Pseudomonas putida TVA8 was higher on nanophase than conventional titania. Importantly, in terms of metabolism, bacteria attached to the nanophase surfaces had higher bioluminescence rates than on the conventional surfaces under all nutrient conditions. Thus, the results from this study show greater select bacterial metabolism on nanometer than conventional topographies, critical results with strong consequences for the design of improved biosensors for bacteria detection. PMID:19337418

  2. Trends in bacterial trehalose metabolism and significant nodes of metabolic pathway in the direction of trehalose accumulation

    PubMed Central

    Ruhal, Rohit; Kataria, Rashmi; Choudhury, Bijan

    2013-01-01

    Summary The current knowledge of trehalose biosynthesis under stress conditions is incomplete and needs further research. Since trehalose finds industrial and pharmaceutical applications, enhanced accumulation of trehalose in bacteria seems advantageous for commercial production. Moreover, physiological role of trehalose is a key to generate stress resistant bacteria by metabolic engineering. Although trehalose biosynthesis requires few metabolites and enzyme reactions, it appears to have a more complex metabolic regulation. Trehalose biosynthesis in bacteria is known through three pathways – OtsAB, TreYZ and TreS. The interconnections of in vivo synthesis of trehalose, glycogen or maltose were most interesting to investigate in recent years. Further, enzymes at different nodes (glucose-6-P, glucose-1-P and NDP-glucose) of metabolic pathways influence enhancement of trehalose accumulation. Most of the study of trehalose biosynthesis was explored in medically significant Mycobacterium, research model Escherichia coli, industrially applicable Corynebacterium and food and probiotic interest Propionibacterium freudenreichii. Therefore, the present review dealt with the trehalose metabolism in these bacteria. In addition, an effort was made to recognize how enzymes at different nodes of metabolic pathway can influence trehalose accumulation. PMID:23302511

  3. Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults.

    PubMed

    Wiseman, Helen; Casey, Karen; Bowey, Elizabeth A; Duffy, Rosanna; Davies, Margaret; Rowland, Ian R; Lloyd, Antony S; Murray, Alistair; Thompson, Richard; Clarke, Don B

    2004-09-01

    Little information is currently available on the role of the gut microflora in modulating isoflavone bioavailability or on sex differences in isoflavone metabolism and bioavailability. We sought to determine whether chronic soy consumption influences isoflavone bioavailability as judged by plasma isoflavone concentrations and modified gut microflora activities [beta-glucoside hydrolysis and equol and O-desmethylangolensin (O-DMA) production]. We also examined whether sex differences in isoflavone metabolism exist. A randomized, parallel, controlled study design was used to compare a high-soy diet (104 +/- 24 mg total isoflavones/d) with a low-soy diet (0.54 +/- 0.58 mg total isoflavones/d) in 76 healthy young adults for 10 wk. Concentrations of isoflavones and their gut microflora metabolites in the plasma, urine, and feces were significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. Concentrations of O-DMA in plasma and urine were higher in the men than in the women. Fecal bacteria from subjects consuming both diets could convert daidzein to equol ex vivo. Fecal beta-glucosidase activity was significantly higher in the subjects who consumed the high-soy diet than in those who consumed the low-soy diet. Although interindividual variation in isoflavone metabolism was high, intraindividual variation was low. Only concentrations of O-DMA in plasma and urine appeared to be influenced by sex. Chronic soy consumption does not appear to induce many significant changes to the gut metabolism of isoflavones other than higher beta-glucosidase activity.

  4. Influence of nutrition on liver oxidative metabolism.

    PubMed

    Jorquera, F; Culebras, J M; González-Gallego, J

    1996-06-01

    The liver plays a major role in the disposition of the majority of drugs. This is due to the presence of several drug-metabolizing enzyme systems, including a group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine metabolism. Different drugs and other factors may induce or inhibit the cytochrome P450-dependent system. This effect is important in terms of the efficacy or toxicity of drugs that are substrates for the system. Microsomal oxidation in animals fed with protein-deficient diets is depressed. The mixed-function oxidase activity recovers after a hyperproteic diet or the addition of lipids. Similar findings have been reported in patients with protein-calorie malnutrition, although results in the elderly are conflicting. Different studies have revealed that microsomal oxidation is impaired by total parenteral nutrition and that this effect is absent when changing the caloric source from carbohydrates to a conventional amino acid solution or after lipid addition, especially when administered as medium-chain/long-chain triglyceride mixtures. Peripheral parenteral nutrition appears to increase antipyrine clearance.

  5. Metabolic and biochemical considerations of bone.

    PubMed

    Lutwak, L

    1975-01-01

    Recognition of the dynamic aspects of bone metabolism can lead to a unified concept involving endocrine and nutritional influences. Although most hormones can influence bone metabolism directly or indirectly, the principal ones involved in skeletal metabolism are parathyroid hormone, calcitonin and 1,25-dihydroxy-vitamin D. The actions of parathyroid hormone and 1,25-dihydroxy-vitamin D result in elevations of circulating extracellular fluid calcium concentration through actions directly on bone, intestine, and kidney. Calcitonin leads to decreases in calcium concentration, primarily by action on bone and kidney. The absorption and retention of calcium by the organism is further influenced by the dietary content of calcium, phosphorus, protein, and fluoride. Chronic dietary deficiencies of calcium and excesses of phosphorus may lead to chronic nutritional secondary hyperparathyroidism with resulting skeletal demineralization. In both experimental animals and in man, the earliest manifestation of this condition may be demineralization of the jaw with resultant paradentosis. Experimental studies in animals and in man have shown that this form of demineralization may be completely reversed by increasing dietary calcium and decreasing dietary phosphrous.

  6. Psychiatrists' follow-up of identified metabolic risk: a mixed-method analysis of outcomes and influences on practice

    PubMed Central

    Patterson, Sue; Freshwater, Kathleen; Goulter, Nicole; Ewing, Julie; Leamon, Boyd; Choudhary, Anand; Moudgil, Vikas; Emmerson, Brett

    2016-01-01

    Aims and method To describe and explain psychiatrists' responses to metabolic abnormalities identified during screening. We carried out an audit of clinical records to assess rates of monitoring and follow-up practice. Semi-structured interviews with 36 psychiatrists followed by descriptive and thematic analyses were conducted. Results Metabolic abnormalities were identified in 76% of eligible patients screened. Follow-up, recorded for 59%, was variable but more likely with four or more abnormalities. Psychiatrists endorse guidelines but ambivalence about responsibility, professional norms, resource constraints and skills deficits as well as patient factors influences practice. Therapeutic optimism and desire to be a ‘good doctor’ supported comprehensive follow-up. Clinical implications Psychiatrists are willing to attend to physical healthcare, and obstacles to recommended practice are surmountable. Psychiatrists seek consensus among stakeholders about responsibilities and a systemic approach addressing the social determinants of health inequities. Understanding patients' expectations is critical to promoting best practice. PMID:27752343

  7. Sleep and metabolic control: waking to a problem?

    PubMed

    Trenell, Michael I; Marshall, Nathaniel S; Rogers, Naomi L

    2007-01-01

    1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.

  8. To boldly gulp: standard metabolic rate and boldness have context-dependent influences on risk-taking to breathe air in a catfish.

    PubMed

    McKenzie, David J; Belão, Thiago C; Killen, Shaun S; Rantin, F Tadeu

    2015-12-01

    The African sharptooth catfish Clarias gariepinus has bimodal respiration, it has a suprabranchial air-breathing organ alongside substantial gills. We used automated bimodal respirometry to reveal that undisturbed juvenile catfish (N=29) breathed air continuously in normoxia, with a marked diurnal cycle. Air breathing and routine metabolic rate (RMR) increased in darkness when, in the wild, this nocturnal predator forages. Aquatic hypoxia (20% air saturation) greatly increased overall reliance on air breathing. We investigated whether two measures of risk taking to breathe air, namely absolute rates of aerial O2 uptake (ṀO2,air) and the percentage of RMR obtained from air (%ṀO2,air), were influenced by individual standard metabolic rate (SMR) and boldness. In particular, whether any influence varied with resource availability (normoxia versus hypoxia) or relative fear of predation (day versus night). Individual SMR, derived from respirometry, had an overall positive influence on ṀO2,air across all contexts but a positive influence on %ṀO2,air only in hypoxia. Thus, a pervasive effect of SMR on air breathing became most acute in hypoxia, when individuals with higher O2 demand took proportionally more risks. Boldness was estimated as time required to resume air breathing after a fearful stimulus in daylight normoxia (Tres). Although Tres had no overall influence on ṀO2,air or %ṀO2,air, there was a negative relationship between Tres and %ṀO2,air in daylight, in normoxia and hypoxia. There were two Tres response groups, 'bold' phenotypes with Tres below 75 min (N=13) which, in daylight, breathed proportionally more air than 'shy' phenotypes with Tres above 115 min (N=16). Therefore, individual boldness influenced air breathing when fear of predation was high. Thus, individual energy demand and personality did not have parallel influences on the emergent tendency to take risks to obtain a resource; their influences varied in strength with context. © 2015

  9. Is There a Genetic Basis to the Development of Alcoholism among Native Americans?

    ERIC Educational Resources Information Center

    Gill, Kathryn

    1992-01-01

    Studies of families, twins, and adoptees support a genetic predisposition to alcoholism. Alcohol metabolism may affect the regulation of alcohol intake, because interference with production or elimination of the alcohol metabolite acetaldehyde has behavioral effects. Ongoing research is examining individual and tribal differences in alcohol…

  10. Metabolic consequences of resistive-type exercise

    NASA Technical Reports Server (NTRS)

    Dudley, G. A.

    1988-01-01

    This brief review concerns acute and chronic metabolic responses to resistive-type exercise (RTE) (i.e., Olympic/power weight lifting and bodybuilding). Performance of RTE presents power output substantially greater (10-15-fold) than that evident with endurance-type exercise. Accordingly, RTE relies heavily on the anaerobic enzyme machinery of skeletal muscle for energy supply, with alterations in the rate of aerobic metabolism being modest. Hydrolysis of high energy phosphate compounds (PC, ATP), glycogenolysis, and glycolysis are evident during an acute bout of RTE as indicated by metabolic markers in mixed fiber type skeletal muscle samples. The type of RTE probably influences the magnitude of these responses since the increase in blood lactate is much greater during a typical "bodybuilding" than "power lifting" session. The influence of RTE training on acute metabolic responses to RTE has received little attention. An individual's inherent metabolic characteristics are apparently sufficient to meet the energy demands of RTE as training of this type does not increase VO2max or substantially alter the content of marker enzymes in mixed fiber type skeletal muscle. Analyses of pools of fast- vs slow-twitch fibers, however, indicate that RTE-induced changes may be fiber type specific. Future studies should better delineate the metabolic responses to RTE and determine whether these are related to the enhanced performance associated with such training.

  11. Influence of plankton metabolism and mixing depth on CO2 dynamics in an Amazon floodplain lake.

    PubMed

    Amaral, João Henrique F; Borges, Alberto V; Melack, John M; Sarmento, Hugo; Barbosa, Pedro M; Kasper, Daniele; de Melo, Michaela L; De Fex-Wolf, Daniela; da Silva, Jonismar S; Forsberg, Bruce R

    2018-07-15

    We investigated plankton metabolism and its influence on carbon dioxide (CO 2 ) dynamics in a central Amazon floodplain lake (Janauacá, 3°23' S, 60°18' W) from September 2015 to May 2016, including a period with exceptional drought. We made diel measurements of CO 2 emissions to the atmosphere with floating chambers and depth profiles of temperature and CO 2 partial pressure (pCO 2 ) at two sites with differing wind exposure and proximity to vegetated habitats. Dissolved oxygen (DO) concentrations were monitored continuously during day and night in clear and dark chambers with autonomous optical sensors to evaluate plankton metabolism. Overnight community respiration (CR), and gross primary production (GPP) rates were higher in clear chambers and positively correlated with chlorophyll-a (Chl-a). CO 2 air-water fluxes varied over 24-h periods with changes in thermal structure and metabolism. Most net daily CO 2 fluxes during low water and mid-rising water at the wind exposed site were into the lake as a result of high rates of photosynthesis. All other measurements indicated net daily release to the atmosphere. Average GPP rates (6.8gCm -2 d -1 ) were high compared with other studies in Amazon floodplain lakes. The growth of herbaceous plants on exposed sediment during an exceptional drought led to large carbon inputs when these areas were flooded, enhancing CR, pCO 2 , and CO 2 fluxes. During the period when the submerged herbaceous vegetation decayed phytoplankton abundance increased and photosynthetic uptake of CO 2 occurred. While planktonic metabolism was often autotrophic (GPP:CR>1), CO 2 out-gassing occurred during most periods investigated indicating other inputs of carbon such as sediments or soils and wetland plants. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Complexity of vitamin E metabolism

    PubMed Central

    Schmölz, Lisa; Birringer, Marc; Lorkowski, Stefan; Wallert, Maria

    2016-01-01

    Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for

  13. Integration of Inhibition Kinetics and Molecular Dynamics Simulations: A Urea-Mediated Folding Study on Acetaldehyde Dehydrogenase 1.

    PubMed

    Xu, Yingying; Lee, Jinhyuk; Lü, Zhi-Rong; Mu, Hang; Zhang, Qian; Park, Yong-Doo

    2016-07-01

    Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes.

  14. Vitamin D3 and its synthetic analogue secocholestra-trien-1,2, 24-triol influence the metabolism and the isomerization of retinoic acid in human keratinocytes.

    PubMed

    Jugert, F K; Roos, T C; Notzon, I; Merk, H F

    1998-01-01

    Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D3 - VD3) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol - TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 mM Ca for 24 h, followed by the addition of 10(-6), 10(-8) or 10(-10) M VD3 or TAC, we added 10(-5) M 13-cis-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD3 (10(-6) M) inhibited the isomerization of 13-cis-RA to all-trans-RA (tretinoin) and 9-cis-RA independently from the Ca concentration in the culture medium. 10(-6)-10(-10) M TAC equally inhibit the 4-hydroxylation of all-trans-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-all-trans-RA, leading to a higher persistence of all-trans-RA, the active hormone. Both VD3 and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD3 which prolongs the persistence of 13-cis-RA, and TAC elevating the intracellular concentration of all-trans-RA.

  15. Metabolic pathway engineering for fatty acid ethyl ester production in Saccharomyces cerevisiae using stable chromosomal integration.

    PubMed

    de Jong, Bouke Wim; Shi, Shuobo; Valle-Rodríguez, Juan Octavio; Siewers, Verena; Nielsen, Jens

    2015-03-01

    Fatty acid ethyl esters are fatty acid derived molecules similar to first generation biodiesel (fatty acid methyl esters; FAMEs) which can be produced in a microbial cell factory. Saccharomyces cerevisiae is a suitable candidate for microbial large scale and long term cultivations, which is the typical industrial production setting for biofuels. It is crucial to conserve the metabolic design of the cell factory during industrial cultivation conditions that require extensive propagation. Genetic modifications therefore have to be introduced in a stable manner. Here, several metabolic engineering strategies for improved production of fatty acid ethyl esters in S. cerevisiae were combined and the genes were stably expressed from the organisms' chromosomes. A wax ester synthase (ws2) was expressed in different yeast strains with an engineered acetyl-CoA and fatty acid metabolism. Thus, we compared expression of ws2 with and without overexpression of alcohol dehydrogenase (ADH2), acetaldehyde dehydrogenase (ALD6) and acetyl-CoA synthetase (acs SE (L641P) ) and further evaluated additional overexpression of a mutant version of acetyl-CoA decarboxylase (ACC1 (S1157A,S659A) ) and the acyl-CoA binding protein (ACB1). The combined engineering efforts of the implementation of ws2, ADH2, ALD6 and acs SE (L641P) , ACC1 (S1157A,S659A) and ACB1 in a S. cerevisiae strain lacking storage lipid formation (are1Δ, are2Δ, dga1Δ and lro1Δ) and β-oxidation (pox1Δ) resulted in a 4.1-fold improvement compared with sole expression of ws2 in S. cerevisiae.

  16. Cereal processing influences postprandial glucose metabolism as well as the GI effect.

    PubMed

    Vinoy, Sophie; Normand, Sylvie; Meynier, Alexandra; Sothier, Monique; Louche-Pelissier, Corinne; Peyrat, Jocelyne; Maitrepierre, Christine; Nazare, Julie-Anne; Brand-Miller, Jeannie; Laville, Martine

    2013-01-01

    Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the "isotope part," and the 13 other subjects were included in the "glycemic part." On test days, subjects received biscuits (low glycemic index [GI], high slowly available glucose [SAG]) or extruded cereals (medium GI, low SAG) as part of a breakfast similar in terms of caloric and macronutrient content. The postprandial phase lasted 270 minutes. The rate of appearance (RaE) of exogenous glucose was significantly lower after consumption of biscuits in the first part of the morning (90-150 minutes) than after consumption of extruded cereals (p ≤ 0.05). Conversely, at 210 minutes, it was significantly higher with biscuits (p ≤ 0.01). For the first 2 hours, plasma glucose and insulin were significantly lower after biscuits during the glycemic part. C-peptide plasma concentrations were significantly lower at 90, 120, and 150 minutes after ingestion of the biscuits (p ≤ 0.05). The consumption of biscuits with a high content of slowly digestible starch reduces the appearance rate of glucose in the first part of the morning and prolongs this release in the late phase of the morning (210 minutes). Our results also emphasize that modulation of glucose availability at breakfast is an important factor for metabolic control throughout the morning in healthy subjects due to the lowering of blood glucose and insulin excursions.

  17. Composition Influences the Pathway but not the Outcome of the Metabolic Response of Bacterioplankton to Resource Shifts

    PubMed Central

    Comte, Jérôme; del Giorgio, Paul A.

    2011-01-01

    Bacterioplankton community metabolism is central to the functioning of aquatic ecosystems, and strongly reactive to changes in the environment, yet the processes underlying this response remain unclear. Here we explore the role that community composition plays in shaping the bacterial metabolic response to resource gradients that occur along aquatic ecotones in a complex watershed in Québec. Our results show that the response is mediated by complex shifts in community structure, and structural equation analysis confirmed two main pathways, one involving adjustments in the level of activity of existing phylotypes, and the other the replacement of the dominant phylotypes. These contrasting response pathways were not determined by the type or the intensity of the gradients involved, as we had hypothesized, but rather it would appear that some compositional configurations may be intrinsically more plastic than others. Our results suggest that community composition determines this overall level of community plasticity, but that composition itself may be driven by factors independent of the environmental gradients themselves, such that the response of bacterial communities to a given type of gradient may alternate between the adjustment and replacement pathways. We conclude that community composition influences the pathways of response in these bacterial communities, but not the metabolic outcome itself, which is driven by the environment, and which can be attained through multiple alternative configurations. PMID:21980410

  18. Genotype influences sulfur metabolism in broccoli (Brassica oleracea L.) under elevated CO2 and NaCl stress.

    PubMed

    Rodríguez-Hernández, María del Carmen; Moreno, Diego A; Carvajal, Micaela; Martínez-Ballesta, María del Carmen

    2014-12-01

    Climatic change predicts elevated salinity in soils as well as increased carbon dioxide dioxide [CO2] in the atmosphere. The present study aims to determine the effect of combined salinity and elevated [CO2] on sulfur (S) metabolism and S-derived phytochemicals in green and purple broccoli (cv. Naxos and cv. Viola, respectively). Elevated [CO2] involved the amelioration of salt stress, especially in cv. Viola, where a lower biomass reduction by salinity was accompanied by higher sodium (Na(+)) and chloride (Cl(-)) compartmentation in the vacuole. Moreover, salinity and elevated [CO2] affected the mineral and glucosinolate contents and the activity of biosynthetic enzymes of S-derived compounds and the degradative enzyme of glucosinolate metabolism, myrosinase, as well as the related amino acids and the antioxidant glutathione (GSH). In cv. Naxos, elevated [CO2] may trigger the antioxidant response to saline stress by means of increased GSH concentration. Also, in cv. Naxos, indolic glucosinolates were more influenced by the NaCl×CO2 interaction whereas in cv. Viola the aliphatic glucosinolates were significantly increased by these conditions. Salinity and elevated [CO2] enhanced the S cellular partitioning and metabolism affecting the myrosinase-glucosinolate system. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Anaerobic biodegradation of 8:2 fluorotelomer alcohol in anaerobic activated sludge: Metabolic products and pathways.

    PubMed

    Li, Fei; Su, Qiangfa; Zhou, Zhenming; Liao, Xiaobin; Zou, Jing; Yuan, Baoling; Sun, Wenjie

    2018-06-01

    The anaerobic biodegradability and metabolic pathways of 8:2 fluorotelomer alcohol (8:2 FTOH) were investigated in anaerobic activated sludge. The biodegradation was well described by a double exponential decay model. 8:2 FTOH was biodegraded to poly- and perfluorinated metabolites with the release of fluoride ion. All polyfluorinated metabolites were intermediate metabolic products and could be further transformed to other metabolites, while perfluorinated metabolites were terminal products. 2H-perfluoro-2-decenoic acid (8:2 FTUA) and perfluorooctanoic acid (PFOA) were verified as the most abundant poly- and perfluorinated metabolites, respectively. Two shorter-chain perfluorinated metabolites, perfluoropentanoic acid (PFPeA) and perfluorobutyric acid (PFBA), were first reported in the biodegradation of 8:2 FTOH. However, the total molar recovery of 8:2 FTOH decreased with increasing incubation time, indicating that there might be some unknown metabolites. Thus, the anaerobic biodegradation pathways were proposed as follows: 8:2 FTOH was oxidized to 8:2 FTUA and 2-perfluorooctyl ethanoic acid (8:2 FTCA) via 2-perfluorooctyl acetaldehyde (8:2 FTAL), and then 8:2 FTUA and 8:2 FTCA were further transformed to 1-perfluoroheptyl ethanol (7:2 sFTOH) via 3-perfluoroheptyl propionic acid (7:3 acid) or/and 3-perfluoroheptyl acrylic acid (7:3 Uacid), and eventually 7:2 sFTOH was further biodegraded to PFOA and other perfluorocarboxylates containing less than eight carbons. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Obesity-associated metabolic changes influence resting and peak heart rate in women and men.

    PubMed

    Strandheim, Astrid; Halland, Hilde; Saeed, Sahrai; Cramariuc, Dana; Hetland, Trude; Lønnebakken, Mai Tone; Gerdts, Eva

    2015-01-01

    To study the relationship between obesity and heart rate (HR) in women and men. We studied 241 overweight and obese subjects without known heart disease. All subjects underwent ergospirometry during maximal exercise testing on treadmill and recording of body composition, electrocardiogram and clinic and ambulatory blood pressure. Women (n = 132) were slightly older and had higher fat mass, but lower weight, blood pressure and prevalence of metabolic syndrome (MetS) than men (n = 109) (all p < 0.05), while prevalences of obesity and hypertension did not differ. A significant interaction between sex and HR was demonstrated (p < 0.05). In multivariate analysis, female sex (β = 0.99, p < 0.01) predicted higher resting HR independent of confounders. Higher resting HR was particularly associated with presence of MetS, hypertension, higher insulin resistance and lower relative muscle mass in men (all p < 0.05). Female sex also predicted higher peak exercise HR (β = 0.48, p < 0.01) independent of confounders. Higher peak exercise HR was particularly associated with higher exercise capacity and lower age and self-reported physical activity in men, while lower HbA1c and absence of obesity were the main covariates in women in multivariate analyses (all p < 0.05). In our study population, obesity and obesity-associated metabolic changes influenced both resting and peak exercise HR.

  1. NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium.

    PubMed

    Subramani, E; Jothiramajayam, M; Dutta, M; Chakravorty, D; Joshi, M; Srivastava, S; Mukherjee, A; Datta Ray, C; Chakravarty, B N; Chaudhury, K

    2016-04-01

    Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity? In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases. As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups. Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls. Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed. Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated

  2. Whole Grains in Amelioration of Metabolic Derangements

    PubMed Central

    Develaraja, Samir; Reddy, Anup; Yadav, Mukesh; Jain, Shalini; Yadav, Hariom

    2017-01-01

    Daily diet influences whole body metabolism, and intricately linked to the prevention or progression of metabolic diseases including obesity, diabetes and cardiovascular diseases. Several epidemiological and large scale studies have shown that diets enriched with whole grains improves metabolic function and protect from the development of metabolic diseases. Direct impact of whole grain diet can be mediated on several levels of metabolic functions i.e. reduced glycemic index, improved fat oxidation potential, increased cholesterol clearance or decreased cholesterol biosynthesis and modulation of gut microbiome. In this article we reviewed several studies indicating the beneficial effects of whole grain diets on metabolic functions, as well as discussed the potential active phytochemicals present in these whole grain foods to contribute in modulation of metabolic function in our body. PMID:28944285

  3. Estrogen Signaling in Metabolic Inflammation

    PubMed Central

    Monteiro, Rosário; Teixeira, Diana; Calhau, Conceição

    2014-01-01

    There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions. PMID:25400333

  4. The Sinorhizobium meliloti RNA chaperone Hfq influences central carbon metabolism and the symbiotic interaction with alfalfa.

    PubMed

    Torres-Quesada, Omar; Oruezabal, Roke I; Peregrina, Alexandra; Jofré, Edgardo; Lloret, Javier; Rivilla, Rafael; Toro, Nicolás; Jiménez-Zurdo, José I

    2010-03-06

    The bacterial Hfq protein is able to interact with diverse RNA molecules, including regulatory small non-coding RNAs (sRNAs), and thus it is recognized as a global post-transcriptional regulator of gene expression. Loss of Hfq has an extensive impact in bacterial physiology which in several animal pathogens influences virulence. Sinorhizobium meliloti is a model soil bacterium known for its ability to establish a beneficial nitrogen-fixing intracellular symbiosis with alfalfa. Despite the predicted general involvement of Hfq in the establishment of successful bacteria-eukaryote interactions, its function in S. meliloti has remained unexplored. Two independent S. meliloti mutants, 2011-3.4 and 1021Deltahfq, were obtained by disruption and deletion of the hfq gene in the wild-type strains 2011 and 1021, respectively, both exhibiting similar growth defects as free-living bacteria. Transcriptomic profiling of 1021Deltahfq revealed a general down-regulation of genes of sugar transporters and some enzymes of the central carbon metabolism, whereas transcripts specifying the uptake and metabolism of nitrogen sources (mainly amino acids) were more abundant than in the wild-type strain. Proteomic analysis of the 2011-3.4 mutant independently confirmed these observations. Symbiotic tests showed that lack of Hfq led to a delayed nodulation, severely compromised bacterial competitiveness on alfalfa roots and impaired normal plant growth. Furthermore, a large proportion of nodules (55%-64%) elicited by the 1021Deltahfq mutant were non-fixing, with scarce content in bacteroids and signs of premature senescence of endosymbiotic bacteria. RT-PCR experiments on RNA from bacteria grown under aerobic and microoxic conditions revealed that Hfq contributes to regulation of nifA and fixK1/K2, the genes controlling nitrogen fixation, although the Hfq-mediated regulation of fixK is only aerobiosis dependent. Finally, we found that some of the recently identified S. meliloti sRNAs co

  5. Plant-endophytes interaction influences the secondary metabolism in Echinacea purpurea (L.) Moench: an in vitro model.

    PubMed

    Maggini, Valentina; De Leo, Marinella; Mengoni, Alessio; Gallo, Eugenia Rosaria; Miceli, Elisangela; Reidel, Rose Vanessa Bandeira; Biffi, Sauro; Pistelli, Luisa; Fani, Renato; Firenzuoli, Fabio; Bogani, Patrizia

    2017-12-05

    The influence of the interaction(s) between the medicinal plant Echinacea purpurea (L.) Moench and its endophytic communities on the production of alkamides is investigated. To mimic the in vivo conditions, we have set up an infection model of axenic in vitro E. purpurea plants inoculated with a pool of bacterial strains isolated from the E. purpurea stems and leaves. Here we show different alkamide levels between control (not-inoculated) and inoculated plants, suggesting that the alkamide biosynthesis may be modulated by the bacterial infection. Then, we have analysed the branched-chain amino acids (BCCA) decarboxylase gene (GenBank Accession #LT593930; the enzymatic source for the amine moiety formation of the alkamides) expression patterns. The expression profile shows a higher expression level in the inoculated E. purpurea tissues than in the control ones. These results suggest that the plant-endophyte interaction can influence plant secondary metabolism affecting the therapeutic properties of E. purpurea.

  6. The Central Nervous System and Bone Metabolism: An Evolving Story.

    PubMed

    Dimitri, Paul; Rosen, Cliff

    2017-05-01

    Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function. The sympathetic nervous system was originally identified as the predominant efferent pathway mediating central signalling to control skeleton metabolism, in part regulated through circadian genes. More recent evidence points to a role of the parasympathetic nervous system in the control of skeletal metabolism either through muscarinic influence of sympathetic nerves in the brain or directly via nicotinic receptors on osteoclasts, thus providing evidence for broader autonomic skeletal regulation. Sensory innervation of bone has also received focus again widening our understanding of the complex neuronal regulation of bone mass. Whilst scientific advance in this field of bone metabolism has been rapid, progress is still required to understand how these model systems work in relation to the multiple confounders influencing skeletal metabolism, and the relative balance in these neuronal systems required for skeletal growth and development in childhood and maintaining skeletal integrity in adulthood.

  7. Influence of different yeast cell wall preparations and their components on performance and immune and metabolic pathways in Clostridium perfringens-challenged broiler chicks

    USDA-ARS?s Scientific Manuscript database

    A study was conducted to evaluate the influence of purification of yeast cell wall (YCW) preparations on broiler performance, and immunogenic and metabolic pathways under microbial challenge. A total of 240 day-of-hatch chicks were distributed among two battery brooder units (48 pens; 5 birds/pen; ...

  8. Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

    PubMed

    Mayers, Jared R; Vander Heiden, Matthew G

    2017-06-15

    Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 3131-4. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. The role of Klotho in energy metabolism

    PubMed Central

    Razzaque, M. Shawkat

    2013-01-01

    A disproportionate expansion of white adipose tissue and abnormal recruitment of adipogenic precursor cells can not only lead to obesity but also impair glucose metabolism, which are both common causes of insulin resistance and diabetes mellitus. The development of novel and effective therapeutic strategies to slow the progression of obesity, diabetes mellitus and their associated complications will require improved understanding of adipogenesis and glucose metabolism. Klotho might have a role in adipocyte maturation and systemic glucose metabolism. Klotho increases adipocyte differentiation in vitro, and mice that lack Klotho activity are lean owing to reduced white adipose tissue accumulation; moreover, mice that lack the Kl gene (which encodes Klotho) are resistant to obesity induced by a high-fat diet. Knockout of Kl in leptin-deficient Lepob/ob mice reduces obesity and increases insulin sensitivity, which lowers blood glucose levels. Energy metabolism might also be influenced by Klotho. However, further studies are needed to explore the possibility that Klotho could be a novel therapeutic target to reduce obesity and related complications, and to determine whether and how Klotho might influence the regulation and function of a related protein, β-Klotho, which is also involved in energy metabolism. PMID:22641000

  10. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    PubMed Central

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G.; Kuipers, Oscar P.; Vinga, Susana; Neves, Ana R.

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence. PMID:26500614

  11. Inflammation in metabolically healthy and metabolically abnormal adolescents: The HELENA study.

    PubMed

    González-Gil, E M; Cadenas-Sanchez, C; Santabárbara, J; Bueno-Lozano, G; Iglesia, I; González-Gross, M; Molnar, D; Gottrand, F; De Henauw, S; Kafatos, A; Widhalm, K; Manios, Y; Siani, A; Amaro-Gahete, F; Rupérez, A I; Cañada, D; Censi, L; Kersting, M; Dallongeville, J; Marcos, A; Ortega, F B; Moreno, L A

    2018-01-01

    Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI. A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed. Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status. Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  12. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

    PubMed

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  13. Metabolic control of redox and redox control of metabolism in plants.

    PubMed

    Geigenberger, Peter; Fernie, Alisdair R

    2014-09-20

    Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and characterizing signaling features thereof. We propose that such information will enable

  14. Influence of Camembert consumption on the composition and metabolism of intestinal microbiota: a study in human microbiota-associated rats.

    PubMed

    Lay, Christophe; Sutren, Malène; Lepercq, Pascale; Juste, Catherine; Rigottier-Gois, Lionel; Lhoste, Evelyne; Lemée, Riwanon; Le Ruyet, Pascale; Doré, Joël; Andrieux, Claude

    2004-09-01

    The objective of the present study was to evaluate the consequence of Camembert consumption on the composition and metabolism of human intestinal microbiota. Camembert cheese was compared with milk fermented by yoghurt starters and Lactobacillus casei as a probiotic reference. The experimental model was the human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group), a diet containing Camembert made from pasteurised milk (HMCp group) or a diet containing fermented milk (HMfm group). The level of micro-organisms from dairy products was measured in faeces using cultures on a specific medium and PCR-temporal temperature gradient gel electrophoresis. The metabolic characteristics of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase activities, and bile acid degradations. The results showed that micro-organisms from cheese comprised 10(5)-10(8) bacteria/g faecal sample in the HMCp group. Lactobacillus species from fermented milk were detected in HMfm rats. Consumption of cheese and fermented milk led to similar changes in bacterial metabolism: a decrease in azoreductase activity and NH3 concentration and an increase in mucolytic activities. However, specific changes were observed: in HMCp rats, the proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was higher; in HMfm rats, alpha and beta-galactosidases were higher than in other groups and both azoreductases and nitrate reductases were lower. The results show that, as for fermented milk, Camembert consumption did not greatly modify the microbiota profile or its major metabolic activities. Ingested micro-organisms were able to survive in part during intestinal transit. These dairy products exert a potentially beneficial influence on intestinal metabolism.

  15. CardioNet: a human metabolic network suited for the study of cardiomyocyte metabolism.

    PubMed

    Karlstädt, Anja; Fliegner, Daniela; Kararigas, Georgios; Ruderisch, Hugo Sanchez; Regitz-Zagrosek, Vera; Holzhütter, Hermann-Georg

    2012-08-29

    Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output. Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes. CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.

  16. Measuring maximum and standard metabolic rates using intermittent-flow respirometry: a student laboratory investigation of aerobic metabolic scope and environmental hypoxia in aquatic breathers.

    PubMed

    Rosewarne, P J; Wilson, J M; Svendsen, J C

    2016-01-01

    Metabolic rate is one of the most widely measured physiological traits in animals and may be influenced by both endogenous (e.g. body mass) and exogenous factors (e.g. oxygen availability and temperature). Standard metabolic rate (SMR) and maximum metabolic rate (MMR) are two fundamental physiological variables providing the floor and ceiling in aerobic energy metabolism. The total amount of energy available between these two variables constitutes the aerobic metabolic scope (AMS). A laboratory exercise aimed at an undergraduate level physiology class, which details the appropriate data acquisition methods and calculations to measure oxygen consumption rates in rainbow trout Oncorhynchus mykiss, is presented here. Specifically, the teaching exercise employs intermittent flow respirometry to measure SMR and MMR, derives AMS from the measurements and demonstrates how AMS is affected by environmental oxygen. Students' results typically reveal a decline in AMS in response to environmental hypoxia. The same techniques can be applied to investigate the influence of other key factors on metabolic rate (e.g. temperature and body mass). Discussion of the results develops students' understanding of the mechanisms underlying these fundamental physiological traits and the influence of exogenous factors. More generally, the teaching exercise outlines essential laboratory concepts in addition to metabolic rate calculations, data acquisition and unit conversions that enhance competency in quantitative analysis and reasoning. Finally, the described procedures are generally applicable to other fish species or aquatic breathers such as crustaceans (e.g. crayfish) and provide an alternative to using higher (or more derived) animals to investigate questions related to metabolic physiology. © 2016 The Fisheries Society of the British Isles.

  17. Ocean acidification adversely influences metabolism, extracellular pH and calcification of an economically important marine bivalve, Tegillarca granosa.

    PubMed

    Zhao, Xinguo; Shi, Wei; Han, Yu; Liu, Saixi; Guo, Cheng; Fu, Wandong; Chai, Xueliang; Liu, Guangxu

    2017-04-01

    Oceanic uptake of CO 2 from the atmosphere has significantly reduced surface seawater pH and altered the carbonate chemistry within, leading to global Ocean Acidification (OA). The blood clam, Tegillarca granosa, is an economically and ecologically significant marine bivalve that is widely distributed along the coastal and estuarine areas of Asia. To investigate the physiological responses to OA, blood clams were exposed to ambient and three reduced seawater pH levels (8.1, 7.8, 7.6 and 7.4) for 40 days, respectively. Results obtained suggest that OA suppresses the feeding activity and aerobic metabolism, but elevates proteins catabolism of blood clams. OA also causes extracellular acidosis and decreases haemolymph Ca 2+ concentration. In addition, our data also suggest that OA impairs the calcification process and inner shell surface integrity. Overall, OA adversely influences metabolism, acid-base status and calcification of blood clams, subsequently leading to a decrease in the fitness of this marine bivalve species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Metabolism in Fungal Pathogenesis

    PubMed Central

    Ene, Iuliana V.; Brunke, Sascha; Brown, Alistair J.P.; Hube, Bernhard

    2014-01-01

    Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. PMID:25190251

  19. The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury

    PubMed Central

    Nyholm, Lena; Howells, Tim; Lewén, Anders; Hillered, Lars; Enblad, Per

    2017-01-01

    Background Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (BtipO2) and cerebral metabolism were also studied. Methods A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, BtipO2) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased BtipO2, and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and BtipO2) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients. PMID:28463046

  20. Metabolism and biochemistry in hypogravity

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.

    1991-01-01

    The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

  1. Cattle temperament influences metabolism: 1. Metabolic response to a glucose tolerance test in beef steers

    USDA-ARS?s Scientific Manuscript database

    Temperamental cattle are behaviorally, physiologically, and immunologically different in comparison to calm cattle. Recently, the metabolic differences between temperamental and calm cattle have begun to be explored; temperamental cattle maintain greater circulating concentrations of non-esterified ...

  2. The keto-enol equilibrium in substituted acetaldehydes: focal-point analysis and ab initio limit

    NASA Astrophysics Data System (ADS)

    Balabin, Roman M.

    2011-10-01

    High-level ab initio electronic structure calculations up to the CCSD(T) theory level, including extrapolations to the complete basis set (CBS) limit, resulted in high precision energetics of the tautomeric equilibrium in 2-substituted acetaldehydes (XH2C-CHO). The CCSD(T)/CBS relative energies of the tautomers were estimated using CCSD(T)/aug-cc-pVTZ, MP3/aug-cc-pVQZ, and MP2/aug-cc-pV5Z calculations with MP2/aug-cc-pVTZ geometries. The relative enol (XHC = CHOH) stabilities (ΔE e,CCSD(T)/CBS) were found to be 5.98 ± 0.17, -1.67 ± 0.82, 7.64 ± 0.21, 8.39 ± 0.31, 2.82 ± 0.52, 10.27 ± 0.39, 9.12 ± 0.18, 5.47 ± 0.53, 7.50 ± 0.43, 10.12 ± 0.51, 8.49 ± 0.33, and 6.19 ± 0.18 kcal mol-1 for X = BeH, BH2, CH3, Cl, CN, F, H, NC, NH2, OCH3, OH, and SH, respectively. Inconsistencies between the results of complex/composite energy computations methods Gn/CBS (G2, G3, CBS-4M, and CBS-QB3) and high-level ab initio methods (CCSD(T)/CBS and MP2/CBS) were found. DFT/aug-cc-pVTZ results with B3LYP, PBE0 (PBE1PBE), TPSS, and BMK density functionals were close to the CCSD(T)/CBS levels (MAD = 1.04 kcal mol-1).

  3. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism

    PubMed Central

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P.

    2013-01-01

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with “stemness,” more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This “two-compartment” metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert “low-risk” breast cancer patients to “high-risk” status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results

  4. Dietary macronutrient distribution influences post-exercise substrate utilization in women: A cross-sectional evaluation of metabolic flexibility

    PubMed Central

    Trexler, Eric T.; Smith-Ryan, Abbie E.; Wingfield, Hailee L.; Blue, Malia N. M.; Roelofs, Erica J.; Hirsch, Katie R.

    2016-01-01

    AIM Metabolic flexibility is the ability to alter substrate utilization in response to substrate availability, which may influence health and performance. The current study evaluated the effects of habitual macronutrient distribution on energy expenditure (EE) and metabolic flexibility in physically active women. METHODS Participants (n=20) completed a 3-day food log and a standardized bout of high-intensity interval training to determine EE and respiratory exchange ratio (RER). EE and RER were measured via indirect calorimetry at rest (PRE) and immediately (IP), 30 minutes (30min), and 60 minutes post-exercise (60min). To evaluate metabolic flexibility, RER changes were calculated from PRE to IP, IP to 30min, and IP to 60min. For each macronutrient, participants were categorized into high- and low-intake groups using a median split. RESULTS No significant correlations were observed between macronutrient distribution and EE when covaried for lean mass (all p≥0.232), and ANCOVAs revealed no significant group × time interactions (all p≥0.241). Fat intake was not associated with ΔRER (all p≥0.477). Correlations between PRO intake and ΔRER approached significance (r=0.373–0.411; p=0.079–0.115), as did inverse associations between CHO and ΔRER (r= −0.404 – −0.409; p=0.084–0.087). Lower RER values were observed in the low-CHO group at 30min and 60min (p=0.030) compared to high-CHO. Higher RER values were observed in the high-PRO group at IP (p=0.042) compared to low-PRO. Estradiol was not correlated with RER at any time point, or different between diet groups (all p>0.401). CONCLUSION Results suggest that high PRO and low CHO intakes are associated with greater metabolic flexibility in women. PMID:26959874

  5. Sex, Gender, and Transgender: Metabolic Impact of Cross Hormone Therapy.

    PubMed

    de Souza Santos, Roberta; Frank, Aaron P; Nelson, Michael Douglas; Garcia, Maurice M; Palmer, Biff F; Clegg, Deborah J

    2017-01-01

    Most preclinical and clinical, animal, and human research has been biased with respect to sex and even more so with respect to gender. In fact, little is known about the impact of sex and even less about the influence of gender on overall metabolic processes. The National Institutes of Health has recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes and to include gender as variables influencing physiological processes such as metabolism. It is therefore critical to understand and appreciate how to incorporate sex and gender in preclinical and clinical research in order to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. In this chapter, we define sex and gender and discuss when sex and gender are not aligned, such as that which occurs in transgender individuals, and how this impacts metabolic processes. We discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes rather than focusing on their relative contributions to metabolism in isolation. This knowledge will optimize therapies specific for individuals which need to encompass sex and gender.

  6. Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

    PubMed Central

    Kim, So-Hyun; K. Cho, Somi; Min, Tae-Sun; Kim, Yujin; Yang, Seung-Ok; Kim, Hee-Su; Hyun, Sun-Hee; Kim, Hana; Kim, Young-Suk; Choi, Hyung-Kyoon

    2011-01-01

    The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake. PMID:21562641

  7. Cereal Processing Influences Postprandial Glucose Metabolism as Well as the GI Effect

    PubMed Central

    Vinoy, Sophie; Normand, Sylvie; Meynier, Alexandra; Sothier, Monique; Louche-Pelissier, Corinne; Peyrat, Jocelyne; Maitrepierre, Christine; Nazare, Julie-Anne; Brand-Miller, Jeannie; Laville, Martine

    2013-01-01

    Objective: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Methods: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the “isotope part,” and the 13 other subjects were included in the “glycemic part.” On test days, subjects received biscuits (low glycemic index [GI], high slowly available glucose [SAG]) or extruded cereals (medium GI, low SAG) as part of a breakfast similar in terms of caloric and macronutrient content. The postprandial phase lasted 270 minutes. Results: The rate of appearance (RaE) of exogenous glucose was significantly lower after consumption of biscuits in the first part of the morning (90–150 minutes) than after consumption of extruded cereals (p ≤ 0.05). Conversely, at 210 minutes, it was significantly higher with biscuits (p ≤ 0.01). For the first 2 hours, plasma glucose and insulin were significantly lower after biscuits during the glycemic part. C-peptide plasma concentrations were significantly lower at 90, 120, and 150 minutes after ingestion of the biscuits (p ≤ 0.05). Conclusion: The consumption of biscuits with a high content of slowly digestible starch reduces the appearance rate of glucose in the first part of the morning and prolongs this release in the late phase of the morning (210 minutes). Our results also emphasize that modulation of glucose availability at breakfast is an important factor for metabolic control throughout the morning in healthy subjects due to the lowering of blood glucose and insulin excursions. PMID:24015715

  8. Cattle temperament influences metabolism:3. Metabolic response to a feed restriction challenge in beef steers

    USDA-ARS?s Scientific Manuscript database

    Recent studies have demonstrated metabolic differences between calm and temperamental cattle. Specifically, Temperamental cattle exhibit greater concentrations of non-esterified fatty acids (NEFAs), decreased blood urea nitrogen (BUN), and decreased insulin sensitivity compared to Calm cattle. It is...

  9. The Tangled Circuitry of Metabolism and Apoptosis

    PubMed Central

    Andersen, Joshua L.; Kornbluth, Sally

    2013-01-01

    For single cell organisms, nutrient uptake and metabolism are at the crux of their most basic decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate within multicellular organisms is also influenced by metabolism; recent studies, triggered in part be an interest tumor metabolism, are beginning to illuminate the mechanisms through which proliferation, death, and metabolism are intertwined. In particular, work on Bcl-2 family proteins suggests that the signaling pathways governing metabolism and apoptosis are inextricably linked. Here, we review the crosstalk between these pathways, emphasizing recent work that illustrates the emerging dual nature of several core apoptotic proteins in regulating both metabolism and cell death. PMID:23395270

  10. Effects of cyanamide and clofibrate on the enzymes of ethanol oxydation and on ethanol consumption in the rat.

    PubMed

    Lamboeuf, Y; De Saint Blanquat, G

    1980-01-01

    The action of cyanamide and of clofibrate was studied on the voluntary drinking behaviour of alcohol intoxicated animals and also on the enzymes of ethyl oxydation. Both substances reduce alcohol consumption by about 35% and cause metabolic modifications: inhibition of aldehyde dehydrogenase and of catalase by cyanamide; activation of alcohol- and aldehyde-dehydrogenases by clofibrate. These effects are constantly found in most of the tissues of the rat. The results are discussed bearing in mind the relationships between alcohol metabolism, acetaldehyde metabolism, the toxicity of alcohol and the drinking behaviour.

  11. Gut microbiota and metabolic syndrome.

    PubMed

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-11-21

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

  12. Epidemiology of Endometrial Carcinoma: Etiologic Importance of Hormonal and Metabolic Influences.

    PubMed

    Felix, Ashley S; Yang, Hannah P; Bell, Daphne W; Sherman, Mark E

    2017-01-01

    Endometrial carcinoma is the most common gynecologic cancer in developed nations, and the annual incidence is projected to increase, secondary to the high prevalence of obesity, a strong endometrial carcinoma risk factor. Although endometrial carcinomas are etiologically, biologically, and clinically diverse, hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid carcinoma, the numerically predominant subtype. The centrality of hormonal and metabolic disturbances in the pathogenesis of endometrial carcinoma, combined with its slow development from well-characterized precursors in most cases, offers a substantial opportunity to reduce endometrial carcinoma mortality through early detection, lifestyle modification, and chemoprevention. In this chapter, we review the epidemiology of endometrial carcinoma, emphasizing theories that link risk factors for these tumors to hormonal and metabolic mechanisms. Future translational research opportunities related to prevention are discussed.

  13. Evaluation of the DNA damaging potential of cannabis cigarette smoke by the determination of acetaldehyde derived N2-ethyl-2'-deoxyguanosine adducts.

    PubMed

    Singh, Rajinder; Sandhu, Jatinderpal; Kaur, Balvinder; Juren, Tina; Steward, William P; Segerbäck, Dan; Farmer, Peter B

    2009-06-01

    Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer. The method required 50 microg of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes. No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis

  14. Intrinsic vs. extrinsic influences on life history expression: metabolism and parentally induced temperature influences on embryo development rate.

    PubMed

    Martin, Thomas E; Ton, Riccardo; Niklison, Alina

    2013-06-01

    Intrinsic processes are assumed to underlie life history expression and trade-offs, but extrinsic inputs are theorised to shift trait expression and mask trade-offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass-specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade-off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade-offs across species. © 2013 John Wiley & Sons Ltd/CNRS.

  15. Intrinsic vs. extrinsic influences on life history expression: metabolism and parentally induced temperature influences on embryo development rate

    USGS Publications Warehouse

    Martin, Thomas E.; Ton, Riccardo; Nikilson, Alina

    2013-01-01

    Intrinsic processes are assumed to underlie life history expression and trade-offs, but extrinsic inputs are theorised to shift trait expression and mask trade-offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass-specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade-off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade-offs across species.

  16. Yeast alter micro-oxygenation of wine: oxygen consumption and aldehyde production.

    PubMed

    Han, Guomin; Webb, Michael R; Richter, Chandra; Parsons, Jessica; Waterhouse, Andrew L

    2017-08-01

    Micro-oxygenation (MOx) is a common winemaking treatment used to improve red wine color development and diminish vegetal aroma, amongst other effects. It is commonly applied to wine immediately after yeast fermentation (phase 1) or later, during aging (phase 2). Although most winemakers avoid MOx during malolactic (ML) fermentation, it is often not possible to avoid because ML bacteria are often present during phase 1 MOx treatment. We investigated the effect of common yeast and bacteria on the outcome of micro-oxygenation. Compared to sterile filtered wine, Saccharomyces cerevisiae inoculation significantly increased oxygen consumption, keeping dissolved oxygen in wine below 30 µg L -1 during micro-oxygenation, whereas Oenococcus oeni inoculation was not associated with a significant impact on the concentration of dissolved oxygen. The unfiltered baseline wine also had both present, although with much higher populations of bacteria and consumed oxygen. The yeast-treated wine yielded much higher levels of acetaldehyde, rising from 4.3 to 29 mg L -1 during micro-oxygenation, whereas no significant difference was found between the bacteria-treated wine and the filtered control. The unfiltered wine exhibited rapid oxygen consumption but no additional acetaldehyde, as well as reduced pyruvate. Analysis of the acetaldehyde-glycerol acetal levels showed a good correlation with acetaldehyde concentrations. The production of acetaldehyde is a key outcome of MOx and it is dramatically increased in the presence of yeast, although it is possibly counteracted by the metabolism of O. oeni bacteria. Additional controlled experiments are necessary to clarify the interaction of yeast and bacteria during MOx treatments. Analysis of the glycerol acetals may be useful as a proxy for acetaldehyde levels. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Acetaldehyde reinforcement and motor reactivity in newborns with or without a prenatal history of alcohol exposure

    PubMed Central

    March, Samanta M.; Culleré, Marcela E.; Abate, Paula; Hernández, José I.; Spear, Norman E.; Molina, Juan C.

    2013-01-01

    Animal models have shown that early ontogeny seems to be a period of enhanced affinity to ethanol. Interestingly, the catalase system that transforms ethanol (EtOH) into acetaldehyde (ACD) in the brain, is more active in the perinatal rat compared to adults. ACD has been found to share EtOH's behavioral effects. The general purpose of the present study was to assess ACD motivational and motor effects in newborn rats as a function of prenatal exposure to EtOH. Experiment 1 evaluated if ACD (0.35 μmol) or EtOH (0.02 μmol) supported appetitive conditioning in newborn pups prenatally exposed to EtOH. Experiment 2 tested if prenatal alcohol exposure modulated neonatal susceptibility to ACD's motor effects (ACD dose: 0, 0.35 and 0.52 μmol). Experiment 1 showed that EtOH and ACD supported appetitive conditioning independently of prenatal treatments. In Experiment 2, latency to display motor activity was altered only in neonates prenatally treated with water and challenged with the highest ACD dose. Prenatal EtOH experience results in tolerance to ACD's motor activity effects. These results show early susceptibility to ACD's appetitive effects and attenuation of motor effects as a function of prenatal history with EtOH, within a stage in development where brain ACD production seems higher than later in life. PMID:23785319

  18. Hypersensitivities for Acetaldehyde and Other Agents among Cancer Cells Null for Clinically Relevant Fanconi Anemia Genes

    PubMed Central

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R.; Rago, Carlo; Bhunia, Anil K.; Hossain, M. Zulfiquer; Paun, Bogdan C.; Ren, Yunzhao R.; Iacobuzio-Donahue, Christine A.; Azad, Nilofer A.; Kern, Scott E.

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. PMID:24200853

  19. Glucokinase Regulatory Protein Genetic Variant Interacts with Omega-3 PUFA to Influence Insulin Resistance and Inflammation in Metabolic Syndrome

    PubMed Central

    Garcia-Rios, Antonio; Mc Monagle, Jolene; Gulseth, Hanne L.; Ordovas, Jose M.; Shaw, Danielle I.; Karlström, Brita; Kiec-Wilk, Beata; Blaak, Ellen E.; Helal, Olfa; Malczewska-Malec, Małgorzata; Defoort, Catherine; Risérus, Ulf; Saris, Wim H. M.; Lovegrove, Julie A.; Drevon, Christian A.; Roche, Helen M.; Lopez-Miranda, Jose

    2011-01-01

    Glucokinase Regulatory Protein (GCKR) plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS) risk. Objective To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP) and n-3 PUFA in MetS subjects. Design Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort. Results Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019), C-peptide (P = 0.004), HOMA-IR (P = 0.008) and CRP (P = 0.032) as compared with subjects carrying the minor T-allele (Leu446). In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele. Conclusions We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals. Trial Registration ClinicalTrials.gov NCT00429195 PMID:21674002

  20. The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

    NASA Astrophysics Data System (ADS)

    Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

    2007-07-01

    It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

  1. The influence of a low air pressure environment on human metabolic rate during short-term (< 2 h) exposures.

    PubMed

    Cui, W; Wang, H; Wu, T; Ouyang, Q; Hu, S; Zhu, Y

    2017-03-01

    Passengers in aircraft cabins are exposed to low-pressure environments. One of the missing links in the research on thermal comfort under cabin conditions is the influence of low air pressure on the metabolic rate. In this research, we simulated the cabin pressure regime in a chamber in which the pressure level could be controlled. Three pressure levels (101/85/70 kPa) were tested to investigate how metabolic rate changed at different pressure levels. The results show that as pressure decreased, the respiratory flow rate (RFR) at standard condition (STPD: 0°C, 101 kPa) significantly decreased. Yet the oxygen (O 2 ) consumption and carbon dioxide (CO 2 ) production significantly increased, as reflected in the larger concentration difference between inhaled and exhaled air. A significant increase in the respiratory quotient (RQ) was also observed. For metabolic rate, no significant increase (P > 0.05) was detected when pressure decreased from 101 kPa to 85 kPa; however, the increase associated with a pressure decrease from 85 kPa to 70kPa was significant (P < 0.05). Empirical equations describing the above parameters are provided, which can be helpful for thermal comfort assessment in short-haul flights. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Development of blueberry liquor: influence of distillate, sweetener and fruit quantity.

    PubMed

    Caldeira, Ilda; Lopes, Daniel; Delgado, Teresa; Canas, Sara; Anjos, Ofélia

    2018-02-01

    In this work different formulations of blueberry liquor were tested and characterised based on their physico-chemical and sensory characteristics. Three factors were evaluated: the distillate used to produce the liquor (wine spirit or grape marc spirit); the sweetener (white sugar or honey) and the fruit quantity (two doses). For each liquor, pH, total acidity, dry soluble solids content, dry extract, alcoholic strength, reducing sugars, colour intensity, methanol content, acetaldehyde and fusel alcohols were determined. Sensory tests were carried out with a trained panel. The three factors studied significantly influenced the physico-chemical features of the liquors, being the quantity of fruit the most discriminating factor, except for the volatile compounds which were mainly influenced by the distillate. As regards the sensory analysis, it was found that the most appreciated liquor was that prepared with wine spirit, sugar and a lower dose of blueberry, and the less appreciated formulation was the one made with grape marc spirit, honey and a lower quantity of blueberry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  3. Environmental and genetic influences on flight metabolic rate in the honey bee, Apis mellifera.

    PubMed

    Harrison, Jon F; Fewell, Jennifer H

    2002-10-01

    Flying honey bees demonstrate highly variable metabolic rates. The lowest reported values (approximately 0.3 Wg(-1)) occur in tethered bees generating the minimum lift to support their body weight, free-flying 2-day old bees, winter bees, or bees flying at high air temperatures (45 degrees C). The highest values (approximately 0.8 Wg(-1)) occur in foragers that are heavily loaded or flying in low-density air. In different studies, flight metabolic rate has increased, decreased, or remained constant with air temperature. Current research collectively suggests that this variation occurs because flight metabolic rates decrease at thorax temperatures above or below 38 degrees C. At 30 degrees C, approximately 30% of colonial energy is spent during typical foraging, so variation in flight metabolic rate can strongly affect colony-level energy balance. Higher air temperatures tend to increase colonial net gain rates, efficiencies and honey storage rates due to lower metabolic rates during flight and in the hive. Variation in flight metabolism has a clear genetic basis. Different genetic strains of honey bees often differ in flight metabolic rate, and these differences in flight physiology can be correlated with foraging effort, suggesting a possible pathway for selection effects on flight metabolism.

  4. [Reference value for metabolic syndrome checkup and some problems].

    PubMed

    Miyake, Noriko

    2009-09-01

    Metabolic syndrome is one of the most important risk factors of atherosclerotic disease, and visceral obesity is regarded as a principle component of metabolic syndrome. Medical checkups for metabolic syndrome were started in 2008 for the purpose of promoting lifestyle modification through health guidance. The original diagnosis of metabolic syndrome in Japan was presented by the Examination Committee of Criteria for Metabolic Syndrome in April 2005. This guideline defines the waist circumference measurement as an essential component, accompanied by at least two of the following three risk factors: dyslipidemia, a raised blood pressure, and glucose intolerance, and these risk factors were based on multiple representative Japanese cohort studies. However, there are some problems with these standards. For example, it is often the case that accurate evaluation is difficult because variable factors such as meals influence the serum triglyceride level. This influences the reliability of the results of cohort studies. In this symposium, problems with this guideline were presented along with an introduction to the cohort study on which the concept of the syndrome was based. I compiled a cohort study related to metabolic syndrome, and pointed out some problems from the viewpoint of clinical laboratory medicine.

  5. The tangled circuitry of metabolism and apoptosis.

    PubMed

    Andersen, Joshua L; Kornbluth, Sally

    2013-02-07

    For single-cell organisms, nutrient uptake and metabolism are central to the fundamental decision of whether to grow or divide. In metazoans, cell fate decisions are more complex: organismal homeostasis must be strictly maintained by balancing cell proliferation and death. Despite this increased complexity, cell fate within multicellular organisms is also influenced by metabolism; recent studies, triggered in part by an interest in tumor metabolism, are beginning to illuminate the mechanisms through which proliferation, death, and metabolism are intertwined. In particular, work on Bcl-2 family proteins suggests that the signaling pathways governing metabolism and apoptosis are inextricably linked. Here we review the crosstalk between these pathways, emphasizing recent work that illustrates the emerging dual nature of several core apoptotic proteins in regulating both metabolism and cell death. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Influence of Neonatal Hypothyroidism on Hepatic Gene Expression and Lipid Metabolism in Adulthood

    PubMed Central

    Bocos, Carlos; Henríquez-Hernández, Luis A.; Kahlon, Nusrat; Herrera, Emilio; Norstedt, Gunnar; Parini, Paolo; Flores-Morales, Amilcar; Fernández-Pérez, Leandro

    2012-01-01

    Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology, but its specific influence in liver is less understood. Here, we studied how CH influences the liver gene expression program in adulthood. Pregnant rats were given the antithyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as reductions in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, the feed efficiency increased in CH, and this was accompanied by significant catch-up growth. On PND80, significant reductions in body mass, tail length, and circulating IGF-I levels remained in CH rats. Conversely, the mRNA levels of known GH target genes were significantly upregulated. The serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARα and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3 replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. PMID:22666351

  7. Metabolic Control of Redox and Redox Control of Metabolism in Plants

    PubMed Central

    Fernie, Alisdair R.

    2014-01-01

    Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

  8. The Sinorhizobium meliloti RNA chaperone Hfq influences central carbon metabolism and the symbiotic interaction with alfalfa

    PubMed Central

    2010-01-01

    Background The bacterial Hfq protein is able to interact with diverse RNA molecules, including regulatory small non-coding RNAs (sRNAs), and thus it is recognized as a global post-transcriptional regulator of gene expression. Loss of Hfq has an extensive impact in bacterial physiology which in several animal pathogens influences virulence. Sinorhizobium meliloti is a model soil bacterium known for its ability to establish a beneficial nitrogen-fixing intracellular symbiosis with alfalfa. Despite the predicted general involvement of Hfq in the establishment of successful bacteria-eukaryote interactions, its function in S. meliloti has remained unexplored. Results Two independent S. meliloti mutants, 2011-3.4 and 1021Δhfq, were obtained by disruption and deletion of the hfq gene in the wild-type strains 2011 and 1021, respectively, both exhibiting similar growth defects as free-living bacteria. Transcriptomic profiling of 1021Δhfq revealed a general down-regulation of genes of sugar transporters and some enzymes of the central carbon metabolism, whereas transcripts specifying the uptake and metabolism of nitrogen sources (mainly amino acids) were more abundant than in the wild-type strain. Proteomic analysis of the 2011-3.4 mutant independently confirmed these observations. Symbiotic tests showed that lack of Hfq led to a delayed nodulation, severely compromised bacterial competitiveness on alfalfa roots and impaired normal plant growth. Furthermore, a large proportion of nodules (55%-64%) elicited by the 1021Δhfq mutant were non-fixing, with scarce content in bacteroids and signs of premature senescence of endosymbiotic bacteria. RT-PCR experiments on RNA from bacteria grown under aerobic and microoxic conditions revealed that Hfq contributes to regulation of nifA and fixK1/K2, the genes controlling nitrogen fixation, although the Hfq-mediated regulation of fixK is only aerobiosis dependent. Finally, we found that some of the recently identified S. meliloti s

  9. Effects of catecholamines on rat myocardial metabolism. I. Influence of catecholamines on energy-rich nucleotides and phosphorylated fraction contents.

    PubMed

    Merouze, P; Gaudemer, Y

    1975-01-01

    1. The influence of catecholamines (adrenaline and noradrenaline) on energy metabolism of the rat myocardium has been studied by incubating slices of this tissue with these hormones and by following the levels of the different phosphorylated fractions and adenylic nucleotides. 2. Similar effects are obtained with both hormones, adrenaline being more effective. 3. Catecholamines decrease significantly the total amount of phosphate while Pi content increases during the first 10 minutes of incubation; labile and residual phosphate contents increase at the beginning of incubation and decrease to the initial values afterwards. 4. ATP and ADP levels decrease significantly with both hormones; however, the effect of noradrenalin on the ATP level needs a longer time of incubation. The ATP/ADP ratios decrease after 5 minutes incubation and the total adenylic nucleotide content is severely decreased (35 per cent with adrenalin, after 20 minutes incubation). 5. Similar results have been obtained with other tissues; these results can explain the decrease of aerobic metabolism we observed under the same conditions.

  10. Chemometric strategy for modeling metabolic biological space along the gastrointestinal tract and assessing microbial influences.

    PubMed

    Martin, François-Pierre J; Montoliu, Ivan; Kochhar, Sunil; Rezzi, Serge

    2010-12-01

    Over the past decade, the analysis of metabolic data with advanced chemometric techniques has offered the potential to explore functional relationships among biological compartments in relation to the structure and function of the intestine. However, the employed methodologies, generally based on regression modeling techniques, have given emphasis to region-specific metabolic patterns, while providing only limited insights into the spatiotemporal metabolic features of the complex gastrointestinal system. Hence, novel approaches are needed to analyze metabolic data to reconstruct the metabolic biological space associated with the evolving structures and functions of an organ such as the gastrointestinal tract. Here, we report the application of multivariate curve resolution (MCR) methodology to model metabolic relationships along the gastrointestinal compartments in relation to its structure and function using data from our previous metabonomic analysis. The method simultaneously summarizes metabolite occurrence and contribution to continuous metabolic signatures of the different biological compartments of the gut tract. This methodology sheds new light onto the complex web of metabolic interactions with gut symbionts that modulate host cell metabolism in surrounding gut tissues. In the future, such an approach will be key to provide new insights into the dynamic onset of metabolic deregulations involved in region-specific gastrointestinal disorders, such as Crohn's disease or ulcerative colitis.

  11. Salicylic Acid Biosynthesis and Metabolism

    PubMed Central

    Dempsey, D'Maris Amick; Vlot, A. Corina; Wildermuth, Mary C.; Klessig, Daniel F.

    2011-01-01

    Salicylic acid (SA) has been shown to regulate various aspects of growth and development; it also serves as a critical signal for activating disease resistance in Arabidopsis thaliana and other plant species. This review surveys the mechanisms involved in the biosynthesis and metabolism of this critical plant hormone. While a complete biosynthetic route has yet to be established, stressed Arabidopsis appear to synthesize SA primarily via an isochorismate-utilizing pathway in the chloroplast. A distinct pathway utilizing phenylalanine as the substrate also may contribute to SA accumulation, although to a much lesser extent. Once synthesized, free SA levels can be regulated by a variety of chemical modifications. Many of these modifications inactivate SA; however, some confer novel properties that may aid in long distance SA transport or the activation of stress responses complementary to those induced by free SA. In addition, a number of factors that directly or indirectly regulate the expression of SA biosynthetic genes or that influence the rate of SA catabolism have been identified. An integrated model, encompassing current knowledge of SA metabolism in Arabidopsis, as well as the influence other plant hormones exert on SA metabolism, is presented. PMID:22303280

  12. Changes in Nutritional Status Impact Immune Cell Metabolism and Function.

    PubMed

    Alwarawrah, Yazan; Kiernan, Kaitlin; MacIver, Nancie J

    2018-01-01

    Immune cell function and metabolism are closely linked. Many studies have now clearly demonstrated that alterations in cellular metabolism influence immune cell function and that, conversely, immune cell function determines the cellular metabolic state. Less well understood, however, are the effects of systemic metabolism or whole organism nutritional status on immune cell function and metabolism. Several studies have demonstrated that undernutrition is associated with immunosuppression, which leads to both increased susceptibility to infection and protection against several types of autoimmune disease, whereas overnutrition is associated with low-grade, chronic inflammation that increases the risk of metabolic and cardiovascular disease, promotes autoreactivity, and disrupts protective immunity. Here, we review the effects of nutritional status on immunity and highlight the effects of nutrition on circulating cytokines and immune cell populations in both human studies and mouse models. As T cells are critical members of the immune system, which direct overall immune response, we will focus this review on the influence of systemic nutritional status on T cell metabolism and function. Several cytokines and hormones have been identified which mediate the effects of nutrition on T cell metabolism and function through the expression and action of key regulatory signaling proteins. Understanding how T cells are sensitive to both inadequate and overabundant nutrients may enhance our ability to target immune cell metabolism and alter immunity in both malnutrition and obesity.

  13. Influences of sampling volume and sample concentration on the analysis of atmospheric carbonyls by 2,4-dinitrophenylhydrazine cartridge.

    PubMed

    Pal, Raktim; Kim, Ki-Hyun

    2008-03-10

    In this study, the analytical bias involved in the application of the 2,4-dinitrophenylhydrazine (2,4-DNPH)-coated cartridge sampling method was investigated for the analysis of five atmospheric carbonyl species (i.e., acetaldehyde, propionaldehyde, butyraldehyde, isovaleraldehyde, and valeraldehyde). In order to evaluate the potential bias of the sampling technique, a series of the laboratory experiments were conducted to cover a wide range of volumes (1-20 L) and concentration levels (approximately 100-2000 ppb in case of acetaldehyde). The results of these experiments were then evaluated in terms of the recovery rate (RR) for each carbonyl species. The detection properties of these carbonyls were clearly distinguished between light and heavy species in terms of RR and its relative standard error (R.S.E.). It also indicates that the studied analytical approach can yield the most reliable pattern for light carbonyls, especially acetaldehyde. When these experimental results were tested further by a two-factor analysis of variance (ANOVA), the analysis based on the cartridge sampling method is affected more sensitively by the concentration levels of samples rather than the sampling volume.

  14. Gut microbiota and metabolic syndrome

    PubMed Central

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-01-01

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

  15. Inter-regional comparison of land-use effects on stream metabolism

    USGS Publications Warehouse

    Bernot, M.J.; Sobota, D.J.; Hall, R.O.; Mulholland, P.J.; Dodds, W.K.; Webster, J.R.; Tank, J.L.; Ashkenas, L.R.; Cooper, L.W.; Dahm, Clifford N.; Gregory, S.V.; Grimm, N. B.; Hamilton, S.K.; Johnson, S.L.; McDowell, W.H.; Meyer, J.L.; Peterson, B.; Poole, G.C.; Maurice, Valett H.M.; Arango, C.; Beaulieu, J.J.; Burgin, A.J.; Crenshaw, C.; Helton, A.M.; Johnson, L.; Merriam, J.; Niederlehner, B.R.; O'Brien, J. M.; Potter, J.D.; Sheibley, R.W.; Thomas, S.M.; Wilson, K.

    2010-01-01

    1. Rates of whole-system metabolism (production and respiration) are fundamental indicators of ecosystem structure and function. Although first-order, proximal controls are well understood, assessments of the interactions between proximal controls and distal controls, such as land use and geographic region, are lacking. Thus, the influence of land use on stream metabolism across geographic regions is unknown. Further, there is limited understanding of how land use may alter variability in ecosystem metabolism across regions.2. Stream metabolism was measured in nine streams in each of eight regions (n = 72) across the United States and Puerto Rico. In each region, three streams were selected from a range of three land uses: agriculturally influenced, urban-influenced, and reference streams. Stream metabolism was estimated from diel changes in dissolved oxygen concentrations in each stream reach with correction for reaeration and groundwater input.3. Gross primary production (GPP) was highest in regions with little riparian vegetation (sagebrush steppe in Wyoming, desert shrub in Arizona/New Mexico) and lowest in forested regions (North Carolina, Oregon). In contrast, ecosystem respiration (ER) varied both within and among regions. Reference streams had significantly lower rates of GPP than urban or agriculturally influenced streams.4. GPP was positively correlated with photosynthetically active radiation and autotrophic biomass. Multiple regression models compared using Akaike's information criterion (AIC) indicated GPP increased with water column ammonium and the fraction of the catchment in urban and reference land-use categories. Multiple regression models also identified velocity, temperature, nitrate, ammonium, dissolved organic carbon, GPP, coarse benthic organic matter, fine benthic organic matter and the fraction of all land-use categories in the catchment as regulators of ER.5. Structural equation modelling indicated significant distal as well as proximal

  16. Factors influencing the grass carp gut microbiome and its effect on metabolism.

    PubMed

    Ni, Jiajia; Yan, Qingyun; Yu, Yuhe; Zhang, Tanglin

    2014-03-01

    Gut microbiota have attracted extensive attention recently because of their important role in host metabolism, immunity and health maintenance. The present study focused on factors affecting the gut microbiome of grass carp (Ctenopharyngodon idella) and further explored the potential effect of the gut microbiome on metabolism. Totally, 43.39 Gb of screened metagenomic sequences obtained from 24 gut samples were fully analysed. We detected 1228 phylotypes (116 Archaea and 1112 Bacteria), most of which belonged to the phyla Firmicutes, Proteobacteria and Fusobacteria. Totally, 41335 of the detected open reading frames (ORFs) were matched to Kyoto Encyclopedia of Genes and Genomes pathways, and carbohydrate and amino acid metabolism was the main matched pathway deduced from the annotated ORFs. Redundancy analysis based on the phylogenetic composition and gene composition of the gut microbiome indicated that gut fullness and feeding (i.e. ryegrass vs. commercial feed, and pond-cultured vs. wild) were significantly related to the gut microbiome. Moreover, many biosynthesis and metabolism pathways of carbohydrates, amino acids and lipids were significantly enhanced by the gut microbiome in ryegrass-fed grass carp. These findings suggest that the metabolic role played by the gut microbiome in grass carp can be affected by feeding. These findings contribute to the field of fish gut microbial ecology and also provide a basis for follow-up functional studies. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  17. Hydrogen bonding interaction of small acetaldehyde clusters studied with core-electron excitation spectroscopy in the oxygen K-edge region

    NASA Astrophysics Data System (ADS)

    Tabayashi, K.; Chohda, M.; Yamanaka, T.; Tsutsumi, Y.; Takahashi, O.; Yoshida, H.; Taniguchi, M.

    2010-06-01

    In order to examine inner-shell electron excitation spectra of molecular clusters with strong multipole interactions, excitation spectra and time-of-flight (TOF) fragment-mass spectra of small acetaldehyde (AA) clusters have been studied under the beam conditions. The TOF spectra at the oxygen K-edge region showed an intense growth of the protonated clusters, MnH+ (M=CH3CHO) in the cluster beams. "cluster-specific" excitation spectra could be generated by monitoring partial-ion-yields of the protonated clusters. The most intense band of O1s→π*CO was found to shift to a higher energy by 0.15 eV relative to the monomer band upon clusterization. X-ray absorption spectra (XAS) were also calculated for the representative dimer configurations using a computer modelling program based on the density functional theory. The XAS prediction for the most stable (non-planar) configuration was found to give a close comparison with the cluster-band shift observed. The band shift was interpreted as being due to the HOMO-LUMO interaction within the complex where a contribution of vibrationally blue-shifting hydrogen bonding could be identified.

  18. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    PubMed

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  19. Influence of nutritional variables and obesity on health and metabolism.

    PubMed

    Azevedo, Fernanda Reis de; Brito, Bruna Cristina

    2012-01-01

    Obesity is a recurring theme in current scientific literature. This can easily be explained by its exponential increase in all layers of society. The popularity of this subject has also given rise to associated questions, which have achieved greater prominence in health-related publications. In order to assess what has been studied in the field of obesity and nutrition, an overview of all articles published on these subjects in some of the main Brazilian scientific journals over the past two years was performed. Among the subthemes selected for this study, those related to childhood obesity attracted attention due to their greater frequency. These were subdivided into: prevalence, intrauterine and breastfeeding influences that may lead to the development of this condition, impact on quality of life, cardiovascular system and metabolism, and possible prevention strategies. Furthermore, issues related to obesity in adults were explored, such as risk factors and new strategies for prevention, with special attention given to the many studies evaluating different aspects of bariatric surgery. Finally, the subject of malnutrition and the impact of the deficiency of specific micronutrients such as selenium, vitamin D, and vitamin B12 were assessed. Based on the results, it was possible to assess the actual importance of obesity and nutrition in health maintenance, and also the several lines of research regarding these issues. Thus, it is essential to create new methods, which must be quick and efficient, to update health professionals involved in the treatment of obesity.

  20. Exploring the quantitative relationship between metabolism and enzymatic phenotype by physiological modeling of glucose metabolism and lactate oxidation in solid tumors

    NASA Astrophysics Data System (ADS)

    Wang, Qian; Vaupel, Peter; Ziegler, Sibylle I.; Shi, Kuangyu

    2015-03-01

    Molecular imaging using PET or hyperpolarized MRI can characterize tumor phenotypes by assessing the related metabolism of certain substrates. However, the interpretation of the substrate turnover in terms of a pathophysiological understanding is not straightforward and only semiquantitative. The metabolism of imaging probes is influenced by a number of factors, such as the microvascular structure or the expression of key enzymes. This study aims to use computational simulation to investigate the relationship between the metabolism behind molecular imaging and the underlying tumor phenotype. The study focused on the pathways of glucose metabolism and lactate oxidation in order to establish the quantitative relationship between the expression of several transporters (GLUT, MCT1 and MCT4), expression of the enzyme hexokinase (HK), microvasculature and the metabolism of glucose or lactate and the extracellular pH distribution. A computational model for a 2D tumor tissue phantom was constructed and the spatio-temporal evolution of related species (e.g. oxygen, glucose, lactate, protons, bicarbonate ions) was estimated by solving reaction-diffusion equations. The proposed model was tested by the verification of the simulation results using in vivo and in vitro literature data. The influences of different expression levels of GLUT, MCT1, MCT4, HK and microvessel distribution on substrate concentrations were analyzed. The major results are consistent with experimental data (e.g. GLUT is more influential to glycolytic flux than HK; extracellular pH is not correlated with MCT expressions) and provide theoretical interpretation of the co-influence of multiple factors of the tumor microenvironment. This computational simulation may assist the generation of hypotheses to bridge the discrepancy between tumor metabolism and the functions of transporters and enzymes. It has the potential to accelerate the development of multi-modal imaging strategies for assessment of tumor

  1. Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

    PubMed

    Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B

    2014-01-01

    In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

  2. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    PubMed

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Recovery of stream ecosystem metabolism from historical agriculture

    Treesearch

    M.E. McTammany; E.F. Benfield; J.R. Webster

    2007-01-01

    Agriculture has influenced southern Appalachian streams for centuries, but recent socioeconomic trends in the region have led to extensive reforestation agricultural land. Stream ecosystem metabolism might recover from agricultural influence as watersheds undergo reforestation, particularly when shade from terrestrial vegetation is restored. We determined historical (...

  4. Formaldehyde and acetaldehyde exposure mitigation in US residences: In-home measurements of ventilation control and source control

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hult, Erin L.; Willem, Henry; Price, Phillip N.

    2014-10-01

    Measurements were taken in new US residences to assess the extent to which ventilation and source control can mitigate formaldehyde exposure. Increasing ventilation consistently lowered indoor formaldehyde concentrations. However, at a reference air exchange rate of 0.35 h -1, increasing ventilation was up to 60% less effective than would be predicted if the emission rate were constant. This is consistent with formaldehyde emission rates decreasing as air concentrations increase, as observed in chamber studies. In contrast, measurements suggest acetaldehyde emission was independent of ventilation rate. To evaluate the effectiveness of source control, formaldehyde concentrations were measured in Leadership in Energymore » and Environmental Design (LEED) certified/Indoor airPLUS homes constructed with materials certified to have low emission rates of volatile organic compounds (VOC). At a reference air exchange rate of 0.35 h -1, and adjusting for home age, temperature and relative humidity, formaldehyde concentrations in homes built with low-VOC materials were 42% lower on average than in reference new homes with conventional building materials. Without adjustment, concentrations were 27% lower in the low-VOC homes. The mean and standard deviation of formaldehyde concentration were 33 μg m-3 and 22 μg m -3 for low-VOC homes and 45 μg m -3 and 30 μg m -3 for conventional.« less

  5. [Carbon sources metabolic characteristics of airborne microbial communities in constructed wetlands].

    PubMed

    Song, Zhi-Wen; Wang, Lin; Xu, Ai-Ling; Wu, Deng-Deng; Xia, Yan

    2015-02-01

    Using BIOLOG-GN plates, this article describes the carbon sources metabolic characteristics of airborne microbial communities in a free surface-flow constructed wetland in different seasons and clarify the correlation between airborne microbial metabolic functions and environmental factors. The average well color development (AWCD), carbon metabolic profiles and McIntosh values of airborne microbial communities in different seasons were quite different. Analysis of the variations showed that AWCD in spring and summer differed significantly from that in autumn and winter (P < 0.01). In the same season, the degree of utilization of different types of carbon by airborne microbes was different. Summer had a significant difference from other seasons (P < 0.05). Dominant communities of airborne microbes in four seasons were carboxylic acids metabolic community, carbohydrates metabolic community, polymers metabolic community and carboxylic acids metabolic community respectively. Principal component analysis showed that the carbon metabolic characteristics of airborne microbial community in autumn were similar to those in winter but different from those in spring and summer. The characteristics of carbon metabolism revealed differences between summer and spring, autumn, or winter. These differences were mainly caused by amines or amides while the differences between spring and autumn or winter were mainly caused by carboxylic acids. Environmental factors, including changes in wind speed, temperature, and humidity acted to influence the carbon sources metabolic properties of airborne microbial community. The dominant environmental factors that acted to influence the carbon sources metabolic properties of airborne microbial community varied between different seasons.

  6. Influence of polymolybdate adsorbates on electrooxidation of ethanol at PtRu nanoparticles: Combined electrochemical, mass spectrometric and X-ray photoelectron spectroscopic studies

    NASA Astrophysics Data System (ADS)

    Gralec, Barbara; Lewera, Adam; Kulesza, Pawel J.

    2016-05-01

    The role Keggin-type phosphomolybdate (PMo12O403-) ions (adsorbed on carbon-supported PtRu, PtRu/C) on electrooxidation of ethanol is addressed here. The combined results obtained using Differential Electrochemical Mass Spectrometry, X-ray Photoelectron Spectroscopy and Cyclic Voltammetry are consistent with the view that presence of the Keggin-type polyoxometallate, phosphomolybdate, ions (adsorbates) leads to enlargement of the current densities associated with electrooxidation of ethanol at potentials greater than 700 mV vs. RHE. This increase of the anodic currents is correlated with the higher acetaldehyde yield which is likely to reflect changes in the reaction kinetics (e.g. more dynamic dehydrogenation of ethanol leading to acetaldehyde) or in the reaction mechanism defined by the preferential surface modification resulting not only in faster kinetics but also in higher selectivity with respect to acetaldehyde production. It is apparent from the spectroscopic data that modification of PtRu/C nanoparticles with phosphomolybdate ions leads to suppression of the formation of Ru surface oxides.

  7. Difference and alteration in pharmacokinetic and metabolic characteristics of low-solubility natural medicines.

    PubMed

    Yan, Shenglei; Liu, Yuying; Feng, Jianfang; Zhao, Hua; Yu, Zhongshu; Zhao, Jing; Li, Yao; Zhang, Jingqing

    2018-05-01

    Drug metabolism plays vital roles in the absorption and pharmacological activity of poorly soluble natural medicines. It is important to choose suitable delivery systems to increase the bioavailability and bioactivity of natural medicines with low solubility by regulating their metabolism and pharmacokinetics. This review investigates recent developments about the metabolic and pharmacokinetic behavior of poorly soluble natural medicines and their delivery systems. Delivery systems, dosage, administration route and drug-drug interactions alter the metabolic pathway, and bioavailability of low-solubility natural medicines to different degrees. Influencing factors such as formulation, dosage, and administration route are discussed. The metabolic reactions, metabolic enzymes, metabolites and pharmacokinetic behaviors of low-solubility natural medicines, and their delivery systems are systematically reviewed. There are various metabolic situations in the case of low-solubility natural medicines. CYP3A4 and CYP2C are the most common metabolic enzymes, and hydroxylation is the most common metabolic reaction of low solubility natural medicines. The stereo isomeric configuration can have a large influence on metabolism. This review will be useful for physicians and pharmacists to guide more accurate treatment with low-solubility natural medicines by increasing drug efficacies and protecting patients from toxic side effects.

  8. Brick by brick: metabolism and tumor cell growth

    PubMed Central

    DeBerardinis, Ralph J.; Sayed, Nabil; Ditsworth, Dara; Thompson, Craig B.

    2008-01-01

    Summary Tumor cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. Classical work in tumor cell metabolism focused on bioenergetics, particularly enhanced glycolysis and suppressed oxidative phosphorylation (the ‘Warburg effect’). But the biosynthetic activities required to create daughter cells are equally important for tumor growth, and recent studies are now bringing these pathways into focus. In this review, we discuss how tumor cells achieve high rates of nucleotide and fatty acid synthesis, how oncogenes and tumor suppressors influence these activities, and how glutamine metabolism enables macromolecular synthesis in proliferating cells. PMID:18387799

  9. Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training

    PubMed Central

    Thompson, Christopher; Wylie, Lee J.; Blackwell, Jamie R.; Fulford, Jonathan; Black, Matthew I.; Kelly, James; McDonagh, Sinead T. J.; Carter, James; Bailey, Stephen J.; Vanhatalo, Anni

    2017-01-01

    We hypothesized that 4 wk of dietary nitrate supplementation would enhance exercise performance and muscle metabolic adaptations to sprint interval training (SIT). Thirty-six recreationally active subjects, matched on key variables at baseline, completed a series of exercise tests before and following a 4-wk period in which they were allocated to one of the following groups: 1) SIT and NO3−-depleted beetroot juice as a placebo (SIT+PL); 2) SIT and NO3−-rich beetroot juice (~13 mmol NO3−/day; SIT+BR); or 3) no training and NO3−-rich beetroot juice (NT+BR). During moderate-intensity exercise, pulmonary oxygen uptake was reduced by 4% following 4 wk of SIT+BR and NT+BR (P < 0.05) but not SIT+PL. The peak work rate attained during incremental exercise increased more in SIT+BR than in SIT+PL (P < 0.05) or NT+BR (P < 0.001). The reduction in muscle and blood [lactate] and the increase in muscle pH from preintervention to postintervention were greater at 3 min of severe-intensity exercise in SIT+BR compared with SIT+PL and NT+BR (P < 0.05). However, the change in severe-intensity exercise performance was not different between SIT+BR and SIT+PL (P > 0.05). The relative proportion of type IIx muscle fibers in the vastus lateralis muscle was reduced in SIT+BR only (P < 0.05). These findings suggest that BR supplementation may enhance some aspects of the physiological adaptations to SIT. NEW & NOTEWORTHY We investigated the influence of nitrate-rich and nitrate-depleted beetroot juice on the muscle metabolic and physiological adaptations to 4 wk of sprint interval training. Compared with placebo, dietary nitrate supplementation reduced the O2 cost of submaximal exercise, resulted in greater improvement in incremental (but not severe-intensity) exercise performance, and augmented some muscle metabolic adaptations to training. Nitrate supplementation may facilitate some of the physiological responses to sprint interval training. PMID:27909231

  10. Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

    PubMed Central

    Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B.

    2014-01-01

    In general, tropical birds have a “slow pace of life,” lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal’s life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species. PMID:24498080

  11. [Influence of ademol on NO metabolism indices in rats with modeling myocardial infarction].

    PubMed

    Khodakivs'kyĭ, O A; Pavlov, S V; Bukhtiiarova, N V

    2013-01-01

    It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base.

  12. Beneficial effect of CETP gene polymorphism in combination with a Mediterranean diet influencing lipid metabolism in metabolic syndrome patients: CORDIOPREV study

    USDA-ARS?s Scientific Manuscript database

    The cholesteryl ester transfer protein (CETP) gene has been implicated in high-density lipoprotein (HDL-C) metabolism. However, little is known about the impact of this gene on metabolic syndrome (MetS) patients and its interaction with diet. Here, we evaluate whether the consumption of a Mediterran...

  13. Influence of dietary nicotinic acid supplementation on lipid metabolism and related gene expression in two distinct broiler breeds of female chickens.

    PubMed

    Jiang, R R; Zhao, G P; Zhao, J P; Chen, J L; Zheng, M Q; Liu, R R; Wen, J

    2014-10-01

    This study aimed to evaluate the influence of supplemental dietary nicotinic acid (NA) on lipid metabolism and hepatic expression of related genes in female chickens of two distinct broiler strains [Arbor Acres (AA) and Beijing-You (BJY)]. The treatments were arranged in a 2 × 4 factorial in a completely randomized design. Day-old females (n = 384) were allocated to four treatments with six cages per treatment and fed diets (basal contained approximately 25 mg NA/kg) supplemented with 0, 30, 60 and 120 mg NA/kg. A sample of 72 birds from each breed was slaughtered and sampled at their different market times (8 week for AA and 16 week for BJY). Arbor Acres broilers had thickness of subcutaneous fat plus the skin (SFS), and plasma concentration of low-density lipoprotein cholesterol (LDLC) and lower percentage of abdominal fat (PAF), plasma concentrations of TG, NEFA and adiponectin than the BJY line. The hepatic transcription of apolipoprotein A-I (ApoA-I), apolipoproteinB (ApoB), and adiponectin was significantly higher in AA broilers than in BJY broilers. In both breeds, BW, PAF, SFS, NEFA and TG were increased with increasing supplementation from 0 to 60 mg NA/kg, but then decreased slightly with 120 mg added NA/kg. With increasing supplementation, hepatic expression and plasma concentrations of adiponectin decreased from 0 to 60 mg added NA/kg and then increased with 120 mg added NA/kg. The expression of ApoA-I and ApoB mRNA showed linear response to dietary supplementation with NA. These findings indicate that: (i) supplementation of NA influenced the lipid metabolism and related gene expression; (ii) when supplemented with 120 mg NA/kg, some pharmacologic actions on lipid metabolism appeared; and (iii) changes in BW and fat deposition appeared to be associated with hepatic expression of adiponectin.

  14. Metabolic engineering of Schizosaccharomyces pombe via CRISPR-Cas9 genome editing for lactic acid production from glucose and cellobiose.

    PubMed

    Ozaki, Aiko; Konishi, Rie; Otomo, Chisako; Kishida, Mayumi; Takayama, Seiya; Matsumoto, Takuya; Tanaka, Tsutomu; Kondo, Akihiko

    2017-12-01

    Modification of the Schizosaccharomyces pombe genome is often laborious, time consuming due to the lower efficiency of homologous recombination. Here, we constructed metabolically engineered S. pombe strains using a CRISPR-Cas9 system and also demonstrated D-lactic acid (D-LA) production from glucose and cellobiose. Genes encoding two separate pyruvate decarboxylases (PDCs), an L-lactic acid dehydrogenase (L-LDH), and a minor alcohol dehydrogenase (SPBC337.11) were disrupted, thereby attenuating ethanol production. To increase the cellular supply of acetyl-CoA, an important metabolite for growth, we introduced genes encoding bacterial acetylating acetaldehyde dehydrogenase enzymes (Escherichia coli MhpF and EutE). D-LA production by the resulting strain was achieved by expressing a Lactobacillus plantarum gene encoding D-lactate dehydrogenase. The engineered strain efficiently consumed glucose and produced D-LA at 25.2 g/L from 35.5 g/L of consumed glucose with a yield of 0.71 g D-LA / g glucose. We further modified this strain by expressing beta-glucosidase by cell surface display; the resulting strain produced D-LA at 24.4 g/L from 30 g/L of cellobiose in minimal medium, with a yield of 0.68 g D-LA / g glucose. To our knowledge, this study represents the first report of a S. pombe strain that was metabolically engineered using a CRISPR-Cas9 system, and demonstrates the possibility of engineering S. pombe for the production of value-added chemicals.

  15. The orphan estrogen-related receptor alpha and metabolic regulation: new frontiers.

    PubMed

    Ranhotra, Harmit S

    2015-01-01

    Metabolic homeostasis during long-term adaptation in animals is primarily achieved by controlling the expression of metabolic genes by a plethora of cellular transcription factors. The nuclear receptor (NR) superfamily in eukaryotes is an assembly of diverse receptors working as transcriptional regulators of multiple genes. The orphan estrogen-related receptor alpha (ERRα) is one such receptor of the NR superfamily with significant influence on numerous metabolic and other genes. Although it is presently unknown as to which endogenous hormones or ligands activate ERRα, nevertheless it regulates a host of genes whose products participate in various metabolic pathways. Studies over the years show new and interesting data that add to the growing knowledge on ERRα and metabolic regulation. For instance, novel findings indicate existence of mTOR/ERRα regulatory axis and also that ERRα control PGC-1α expression which potentially have significant impact on cellular metabolism. Data show that ERRα exerts its metabolic control by regulating the expression of SIRT5 that influences oxygen consumption and ATP generation. Moreover, ERRα has a role in creatine and lactate uptake in skeletal muscle which is important towards energy generation and contraction. This review is focused on the new insights gained into ERRα regulation of metabolism, networks and pathways that have important consequences in maintaining metabolic homeostasis including development of cancer.

  16. Influence of formulation and processing on absorption and metabolism of flavan-3-ols from tea and cocoa.

    PubMed

    Neilson, Andrew P; Ferruzzi, Mario G

    2011-01-01

    Flavan-3-ols are a major subclass of the class of plant phytochemicals known as flavonoids. Flavan-3-ols are commonly found in fruit, vegetable, and botanical products, including tea, cocoa, grapes, and apples. Both monomeric catechins and polymeric procyanidins are common in the diet, along with several derivatives produced by degradation of these species during processing. Both epidemiological and biological evidence suggests a health-protective role for dietary flavan-3-ols, leading to increased interest in the bioavailability of these compounds from foods. Flavan-3-ol bioavailability depends on numerous factors, including digestive release, absorption, metabolism, and elimination. In addition to these in vivo factors, the complexity of whole-food systems (physical form, flavan-3-ol form and dose, macronutrient and micronutrient profile, processing, etc.) influences the absorption efficiency and circulating profile of flavan-3-ols. An understanding of how food matrices may influence flavan-3-ol absorption will provide a framework to design and develop functional products that positively affect flavan-3-ol absorption and, by extension, potential bioactivity.

  17. Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

    PubMed

    Tirabassi, G; Chelli, F M; Ciommi, M; Lenzi, A; Balercia, G

    2016-01-01

    Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. FH may determine a worsening of the metabolic profile in DM-associated hypogonadism. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by

  18. Mood state and cerebral metabolism in persons with age-associated memory impairment.

    PubMed

    Cherrier, M M; Small, G W; Komo, S; La Rue, A

    1997-12-30

    People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4 +/- 9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.

  19. Paternal epigenetic programming: evolving metabolic disease risk.

    PubMed

    Hur, Suzy S J; Cropley, Jennifer E; Suter, Catherine M

    2017-04-01

    Parental health or exposures can affect the lifetime health outcomes of offspring, independently of inherited genotypes. Such 'epigenetic' effects occur over a broad range of environmental stressors, including defects in parental metabolism. Although maternal metabolic effects are well documented, it has only recently been established that that there is also an independent paternal contribution to long-term metabolic health. Both paternal undernutrition and overnutrition can induce metabolic phenotypes in immediate offspring, and in some cases, the induced phenotype can affect multiple generations, implying inheritance of an acquired trait. The male lineage transmission of metabolic disease risk in these cases implicates a heritable factor carried by sperm. Sperm-based transmission provides a tractable system to interrogate heritable epigenetic factors influencing metabolism, and as detailed here, animal models of paternal programming have already provided some significant insights. Here, we review the evidence for paternal programming of metabolism in humans and animal models, and the available evidence on potential underlying mechanisms. Programming by paternal metabolism can be observed in multiple species across animal phyla, suggesting that this phenomenon may have a unique evolutionary significance. © 2017 Society for Endocrinology.

  20. Stress-resistant neural stem cells positively influence regional energy metabolism after spinal cord injury in mice.

    PubMed

    Schwerdtfeger, Karsten; Mautes, Angelika E M; Bernreuther, Christian; Cui, Yifang; Manville, Jérôme; Dihné, Marcel; Blank, Simon; Schachner, Melitta

    2012-02-01

    The importance of stem cells to ameliorate the devastating consequences of traumatic injuries in the adult mammalian central nervous system calls for improvements in the capacity of these cells to cope, in particular, with the host response to the injury. We have previously shown, however, that in the acutely traumatized spinal cord local energy metabolism led to decreased ATP levels after neural stem cell (NSC) transplantation. As this might counteract NSC-mediated regenerative processes, we investigated if NSC selected for increased oxidative stress resistance are better suited to preserve local energy content. For this purpose, we exposed wild-type (WT) NSC to hydrogen peroxide prior to transplantation. We demonstrate here that transplantation of WT-NSC into a complete spinal cord compression injury model even lowers the ATP content beyond the level detected in spinal cord injury-control animals. Compared to WT-NSC, stress-resistant (SR) NSC did not lead to a further decrease in ATP content. These differences between WT- and SR-NSC were observed 4 h after the lesion with subsequent transplantation. At 24 h after lesioning, these differences were no more as obvious. Thus, in contrast to native NSC, transplantation of NSC selected for oxidative stress resistance can positively influence local energy metabolism in the first hours after spinal cord compression. The functional relevance of this observation has to be tested in further experiments.

  1. Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk.

    PubMed

    Northwood, Emma L; Elliott, Faye; Forman, David; Barrett, Jennifer H; Wilkie, Murray J V; Carey, Francis A; Steele, Robert J C; Wolf, Roland; Bishop, Timothy; Smith, Gillian

    2010-05-01

    We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported. CRA risk was inversely associated with fruit (P=0.02, test for trend) and vegetable (P=0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala114Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P=0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His139Arg) genotype was noted (P=0.02 for interaction). We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation.

  2. Famine versus feast: understanding the metabolism of tumors in vivo.

    PubMed

    Mayers, Jared R; Vander Heiden, Matthew G

    2015-03-01

    To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. COMPARISON OF IN VITRO METHODS AND THE IN VIVO METABOLISM OF LINDANE FOR ASSESSING THE EFFECTS OF REPEATED ADMINISTRATION OF ETHANOL ON HEPATIC DRUG METABOLISM

    EPA Science Inventory

    In vitro methods of assessing alterations in drug metabolism and the measurement of lindane metabolites in urine were compared for their ability to determine the influence of ethanol on drug metabolism. Ethanol was administered to young adult female rats daily for seven days at d...

  4. Intrinsic and extrinsic influences on standard metabolic rates of three species of Australian otariid

    PubMed Central

    Slip, David J.; Harcourt, Robert G.

    2017-01-01

    Abstract The study of marine mammal energetics can shed light on how these animals might adapt to changing environments. Their physiological potential to adapt will be influenced by extrinsic factors, such as temperature, and by intrinsic factors, such as sex and reproduction. We measured the standard metabolic rate (SMR) of males and females of three Australian otariid species (two Australian fur seals, three New Zealand fur seals and seven Australian sea lions). Mean SMR ranged from 0.47 to 1.05 l O2 min−1, which when adjusted for mass was from 5.33 to 7.44 ml O2 min−1 kg−1. We found that Australian sea lion mass-specific SMR (sSMR; in millilitres of oxygen per minute per kilogram) varied little in response to time of year or moult, but was significantly influenced by sex and water temperature. Likewise, sSMR of Australian and New Zealand fur seals was also influenced by sex and water temperature, but also by time of year (pre-moult, moult or post-moult). During the moult, fur seals had significantly higher sSMR than at other times of the year, whereas there was no discernible effect of moult for sea lions. For both groups, females had higher sSMR than males, but sea lions and fur seals showed different responses to changes in water temperature. The sSMR of fur seals increased with increasing water temperature, whereas sSMR of sea lions decreased with increasing water temperature. There were no species differences when comparing animals of the same sex. Our study suggests that fur seals have more flexibility in their physiology than sea lions, perhaps implying that they will be more resilient in a changing environment. PMID:28852504

  5. Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice.

    PubMed

    Makarova, Elena N; Chepeleva, Elena V; Panchenko, Polina E; Bazhan, Nadezhda M

    2013-12-01

    Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A(y) mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL-A(y) and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A(y) mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A(y) mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.

  6. Metabolic State Alters Economic Decision Making under Risk in Humans

    PubMed Central

    Drew, Megan E.; Batterham, Rachel L.; Dolan, Raymond J.

    2010-01-01

    Background Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity

  7. Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood-stabilizers.

    PubMed

    Tournier, Marie; Bégaud, Bernard; Cougnard, Audrey; Auleley, Guy-Robert; Deligne, Jean; Blum-Boisgard, Claudine; Thiébaut, Anne C M; Verdoux, Hélène

    2012-07-01

    Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in

  8. Microbial contributions to chronic inflammation and metabolic disease.

    PubMed

    Shanahan, Fergus; Sheehan, Donal

    2016-07-01

    It is long known that immune and metabolic cascades intersect at various cross-points. More recently, the regulatory influence of the microbiota on both of these cascades has emerged. Advances with therapeutic implications for chronic immunologic and metabolic disorders are examined. Disturbances of the microbiota, particularly in early life, may be the proximate environmental risk factor in socioeconomically developed societies for development of chronic immune-allergic and metabolic disorders, including obesity. Antibiotics and dietary factors contribute to this risk. Multiple microbial signalling molecules mediate host-microbe interactions including bacterial metabolites such as short-chain fatty acids, bile salts and others. New strategies for manipulating the composition and metabolic activity of the gut microbiota have emerged and offer a realistic prospect of personalized therapeutic options in immune and metabolic diseases.

  9. The role of leptin in regulating bone metabolism

    PubMed Central

    Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.

    2015-01-01

    Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature on indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk – benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. PMID:25497343

  10. The role of leptin in regulating bone metabolism.

    PubMed

    Upadhyay, Jagriti; Farr, Olivia M; Mantzoros, Christos S

    2015-01-01

    Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature the indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk-benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. Copyright © 2015. Published by Elsevier Inc.

  11. Possible stimuli for strength and power adaptation : acute metabolic responses.

    PubMed

    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

    The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

  12. Flavanol plasma bioavailability is affected by metabolic syndrome in rats.

    PubMed

    Margalef, Maria; Pons, Zara; Iglesias-Carres, Lisard; Bravo, Francisca Isabel; Muguerza, Begoña; Arola-Arnal, Anna

    2017-09-15

    Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state influenced flavanol plasma bioavailability. Standard and cafeteria (CAF) diet fed rats, a robust model of metabolic syndrome (MeS), were administered 1000mg/kg of flavanol enriched grape seed polyphenol extract (GSPE). Flavanols and their metabolites were quantified by HPLC-MS/MS in plasma before and at 2, 4, 7, 24, and 48h after GSPE ingestion. Results showed that in CAF administered rats the maximum time of plasma flavanol concentration was delayed and these animals presented higher levels of plasma phase-II metabolites as well as altered microbial metabolites. In conclusion, this study demonstrated that MeS pathological state modified flavanol bioavailability, supporting the hypothesis that flavanol metabolism, and therefore flavanol functionality, depend on the organism's state of health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Developmental programming of the metabolic syndrome - critical windows for intervention

    PubMed Central

    Vickers, Mark H

    2011-01-01

    Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment. PMID:21954418

  14. Trehalose metabolism in plants.

    PubMed

    Lunn, John Edward; Delorge, Ines; Figueroa, Carlos María; Van Dijck, Patrick; Stitt, Mark

    2014-08-01

    Trehalose is a quantitatively important compatible solute and stress protectant in many organisms, including green algae and primitive plants. These functions have largely been replaced by sucrose in vascular plants, and trehalose metabolism has taken on new roles. Trehalose is a potential signal metabolite in plant interactions with pathogenic or symbiotic micro-organisms and herbivorous insects. It is also implicated in responses to cold and salinity, and in regulation of stomatal conductance and water-use efficiency. In plants, as in other eukaryotes and many prokaryotes, trehalose is synthesized via a phosphorylated intermediate, trehalose 6-phosphate (Tre6P). A meta-analysis revealed that the levels of Tre6P change in parallel with sucrose, which is the major product of photosynthesis and the main transport sugar in plants. We propose the existence of a bi-directional network, in which Tre6P is a signal of sucrose availability and acts to maintain sucrose concentrations within an appropriate range. Tre6P influences the relative amounts of sucrose and starch that accumulate in leaves during the day, and regulates the rate of starch degradation at night to match the demand for sucrose. Mutants in Tre6P metabolism have highly pleiotropic phenotypes, showing defects in embryogenesis, leaf growth, flowering, inflorescence branching and seed set. It has been proposed that Tre6P influences plant growth and development via inhibition of the SNF1-related protein kinase (SnRK1). However, current models conflict with some experimental data, and do not completely explain the pleiotropic phenotypes exhibited by mutants in Tre6P metabolism. Additional explanations for the diverse effects of alterations in Tre6P metabolism are discussed. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  15. Seasonal influence over serum and urine metabolic markers in submariners during prolonged patrols

    PubMed Central

    Holy, Xavier; Bégot, Laurent; Renault, Sylvie; Butigieg, Xavier; André, Catherine; Bonneau, Dominique; Savourey, Gustave; Collombet, Jean-Marc

    2015-01-01

    Within the framework of earlier publications, we have consistently dedicated our investigations to eliciting the effects of both seasonal vitamin D deficiency and submarine-induced hypercapnia on serum parameters for acid–base balance and bone metabolism in submariners over a 2-month winter (WP) or summer (SP) patrols. The latest findings reported herein, contribute further evidence with regard to overall physiological regulations in the same submariner populations that underwent past scrutiny. Hence, urine and blood samples were collected in WP and SP submariners at control prepatrol time as well as on submarine patrol days 20, 41, and 58. Several urine and serum metabolic markers were quantified, namely, deoxypyridinoline (DPD), lactate, albumin, creatinine, nonesterified fatty acids (NEFA), and ionized sodium (Na+) or potassium (K+), with a view to assessing bone, muscle, liver, or kidney metabolisms. We evidenced bone metabolism alteration (urine DPD, calcium, and phosphorus) previously recorded in submarine crewmembers under prolonged patrols. We also highlighted transitory modifications in liver metabolism (serum albumin) occurring within the first 20 days of submersion. We further evidenced changes in submariners’ renal physiology (serum creatinine) throughout the entire patrol time span. Measurements of ionic homeostasis (serum Na+ and K+) displayed potential seasonal impact over active ionic pumps in submariners. Finally, there is some evidence that submersion provides beneficial conditions prone to fend off seasonal lactic acidosis (serum lactate) detected in WP submariners. PMID:26265754

  16. Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin".

    PubMed

    Pruimboom, Leo; Ruiz-Núñez, Begoña; Raison, Charles L; Muskiet, Frits A J

    2016-01-01

    Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders.

  17. Direct antioxidant properties of methotrexate: Inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging.

    PubMed

    Zimmerman, Matthew C; Clemens, Dahn L; Duryee, Michael J; Sarmiento, Cleofes; Chiou, Andrew; Hunter, Carlos D; Tian, Jun; Klassen, Lynell W; O'Dell, James R; Thiele, Geoffrey M; Mikuls, Ted R; Anderson, Daniel R

    2017-10-01

    Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, supporting the concept that MAA-adducts not only serve as markers of oxidative stress but may have a direct role in the pathogenesis of inflammatory diseases. Because MAA-adducts are commonly detected in diseased tissues and are proposed to mitigate disease progression in both RA and CVD, we tested the hypothesis that MTX inhibits the generation of MAA-protein adducts by scavenging reactive oxygen species. Using a cell free system, we found that MTX reduces MAA-adduct formation by approximately 6-fold, and scavenges free radicals produced during MAA-adduct formation. Further investigation revealed that MTX directly scavenges superoxide, but not hydrogen peroxide. Additionally, using the Nrf2/ARE luciferase reporter cell line, which responds to intracellular redox changes, we observed that MTX inhibits the activation of Nrf2 in cells treated with MDA and AA. These studies define previously unrecognized mechanisms by which MTX can reduce inflammation and subsequent tissue damage, namely, scavenging free radicals, reducing oxidative stress, and inhibiting MAA-adduct formation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

    PubMed

    Yin, Jinbao; Liu, Su; Yu, Jing; Wu, Bing

    2017-07-01

    Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

  19. Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions.

    PubMed

    He, Tianliang; Li, Hongyun; Zhang, Xiaobo

    2017-07-11

    Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. IMPORTANCE Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found

  20. Influence of Sulforaphane Metabolites on Activities of Human Drug-Metabolizing Cytochrome P450 and Determination of Sulforaphane in Human Liver Cells.

    PubMed

    Vanduchova, Alena; Tomankova, Veronika; Anzenbacher, Pavel; Anzenbacherova, Eva

    2016-12-01

    The influence of metabolites of sulforaphane, natural compounds present in broccoli (Brassica oleracea var. botrytis italica) and in other cruciferous vegetables, on drug-metabolizing cytochrome P450 (CYP) enzymes in human liver microsomes and possible entry of sulforaphane into human hepatic cells were investigated. Metabolites studied are compounds derived from sulforaphane by the mercapturic acid pathway (conjugation with glutathione and by following reactions), namely sulforaphane glutathione and sulforaphane cysteine conjugates and sulforaphane-N-acetylcysteine. Their possible effect on four drug-metabolizing CYP enzymes, CYP3A4 (midazolam 1'-hydroxylation), CYP2D6 (bufuralol 1'-hydroxylation), CYP1A2 (7-ethoxyresorufin O-deethylation), and CYP2B6 (7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation), was tested. Inhibition of four prototypical CYP activities by sulforaphane metabolites was studied in pooled human liver microsomes. Sulforaphane metabolites did not considerably affect biological function of drug-metabolizing CYPs in human liver microsomes except for CYP2D6, which was found to be inhibited down to 73-78% of the original activity. Analysis of the entry of sulforaphane into human hepatocytes was done by cell disruption by sonication, methylene chloride extraction, and modified high-performance liquid chromatography method. The results have shown penetration of sulforaphane into the human hepatic cells.

  1. Revising the Representation of Fatty Acid, Glycerolipid, and Glycerophospholipid Metabolism in the Consensus Model of Yeast Metabolism

    PubMed Central

    Aung, Hnin W.; Henry, Susan A.

    2013-01-01

    Abstract Genome-scale metabolic models are built using information from an organism's annotated genome and, correspondingly, information on reactions catalyzed by the set of metabolic enzymes encoded by the genome. These models have been successfully applied to guide metabolic engineering to increase production of metabolites of industrial interest. Congruity between simulated and experimental metabolic behavior is influenced by the accuracy of the representation of the metabolic network in the model. In the interest of applying the consensus model of Saccharomyces cerevisiae metabolism for increased productivity of triglycerides, we manually evaluated the representation of fatty acid, glycerophospholipid, and glycerolipid metabolism in the consensus model (Yeast v6.0). These areas of metabolism were chosen due to their tightly interconnected nature to triglyceride synthesis. Manual curation was facilitated by custom MATLAB functions that return information contained in the model for reactions associated with genes and metabolites within the stated areas of metabolism. Through manual curation, we have identified inconsistencies between information contained in the model and literature knowledge. These inconsistencies include incorrect gene-reaction associations, improper definition of substrates/products in reactions, inappropriate assignments of reaction directionality, nonfunctional β-oxidation pathways, and missing reactions relevant to the synthesis and degradation of triglycerides. Suggestions to amend these inconsistencies in the Yeast v6.0 model can be implemented through a MATLAB script provided in the Supplementary Materials, Supplementary Data S1 (Supplementary Data are available online at www.liebertpub.com/ind). PMID:24678285

  2. Insights into glycogen metabolism in Lactobacillus acidophilus: impact on carbohydrate metabolism, stress tolerance and gut retention.

    PubMed

    Goh, Yong Jun; Klaenhammer, Todd R

    2014-11-20

    In prokaryotic species equipped with glycogen metabolism machinery, the co-regulation of glycogen biosynthesis and degradation has been associated with the synthesis of energy storage compounds and various crucial physiological functions, including global cellular processes such as carbon and nitrogen metabolism, energy sensing and production, stress response and cell-cell communication. In addition, the glycogen metabolic pathway was proposed to serve as a carbon capacitor that regulates downstream carbon fluxes, and in some microorganisms the ability to synthesize intracellular glycogen has been implicated in host persistence. Among lactobacilli, complete glycogen metabolic pathway genes are present only in select species predominantly associated with mammalian hosts or natural environments. This observation highlights the potential involvement of glycogen biosynthesis in probiotic activities and persistence of intestinal lactobacilli in the human gastrointestinal tract. In this review, we summarize recent findings on (i) the presence and potential ecological distribution of glycogen metabolic pathways among lactobacilli, (ii) influence of carbon substrates and growth phases on glycogen metabolic gene expression and glycogen accumulation in L. acidophilus, and (iii) the involvement of glycogen metabolism on growth, sugar utilization and bile tolerance. Our present in vivo studies established the significance of glycogen biosynthesis on the competitive retention of L. acidophilus in the mouse intestinal tract, demonstrating for the first time that the ability to synthesize intracellular glycogen contributes to gut fitness and retention among probiotic microorganisms.

  3. Starmerella bombicola influences the metabolism of Saccharomyces cerevisiae at pyruvate decarboxylase and alcohol dehydrogenase level during mixed wine fermentation

    PubMed Central

    2012-01-01

    Background The use of a multistarter fermentation process with Saccharomyces cerevisiae and non-Saccharomyces wine yeasts has been proposed to simulate natural must fermentation and to confer greater complexity and specificity to wine. In this context, the combined use of S. cerevisiae and immobilized Starmerella bombicola cells (formerly Candida stellata) was assayed to enhance glycerol concentration, reduce ethanol content and to improve the analytical composition of wine. In order to investigate yeast metabolic interaction during controlled mixed fermentation and to evaluate the influence of S. bombicola on S. cerevisiae, the gene expression and enzymatic activity of two key enzymes of the alcoholic fermentation pathway such as pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) were studied. Results The presence of S. bombicola immobilized cells in a mixed fermentation trial confirmed an increase in fermentation rate, a combined consumption of glucose and fructose, an increase in glycerol and a reduction in the production of ethanol as well as a modification in the fermentation of by products. The alcoholic fermentation of S. cerevisiae was also influenced by S. bombicola immobilized cells. Indeed, Pdc1 activity in mixed fermentation was lower than that exhibited in pure culture while Adh1 activity showed an opposite behavior. The expression of both PDC1 and ADH1 genes was highly induced at the initial phase of fermentation. The expression level of PDC1 at the end of fermentation was much higher in pure culture while ADH1 level was similar in both pure and mixed fermentations. Conclusion In mixed fermentation, S. bombicola immobilized cells greatly affected the fermentation behavior of S. cerevisiae and the analytical composition of wine. The influence of S. bombicola on S. cerevisiae was not limited to a simple additive contribution. Indeed, its presence caused metabolic modifications during S. cerevisiae fermentation causing variation in the gene

  4. Establishment of a Quick and Highly Accurate Breath Test for ALDH2 Genotyping

    PubMed Central

    Aoyama, Ikuo; Ohashi, Shinya; Amanuma, Yusuke; Hirohashi, Kenshiro; Mizumoto, Ayaka; Funakoshi, Makiko; Tsurumaki, Mihoko; Nakai, Yukie; Tanaka, Katsuyuki; Hanada, Mariko; Uesaka, Aki; Chiba, Tsutomu; Muto, Manabu

    2017-01-01

    Objectives: Acetaldehyde, the first metabolite of ethanol, is a definite carcinogen for the esophagus, head, and neck; and aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that catalyzes the metabolism of acetaldehyde. The ALDH2 genotype exists as ALDH2*1/*1 (active ALDH2), ALDH2*1/*2 (heterozygous inactive ALDH2), and ALDH2*2/*2 (homozygous inactive ALDH2). Many epidemiological studies have reported that ALDH2*2 carriers are at high risk for esophageal or head and neck squamous cell carcinomas by habitual drinking. Therefore, identification of ALDH2*2 carriers would be helpful for the prevention of those cancers, but there have been no methods suitable for mass screening to identify these individuals. Methods: One hundred and eleven healthy volunteers (ALDH2*1/*1 carriers: 53; ALDH2*1/*2 carriers: 48; and ALDH2*2/*2 carriers: 10) were recruited. Breath samples were collected after drinking 100 ml of 0.5% ethanol using specially designed gas bags, and breath ethanol and acetaldehyde levels were measured by semiconductor gas chromatography. Results: The median (range) breath acetaldehyde levels at 1 min after alcohol ingestion were 96.1 (18.1–399.0) parts per billion (p.p.b.) for the ALDH2*1/*1 genotype, 333.5 (78.4–1218.4) p.p.b. for the ALDH2*1/*2 genotype, and 537.1 (213.2–1353.8) p.p.b. for the ALDH2*2/*2 genotype. The breath acetaldehyde levels in ALDH2*2 carriers were significantly higher than for the ALDH2*1/*1 genotype. Notably, the ratio of breath acetaldehyde level-to-breath ethanol level could identify carriers of the ALDH2*2 allele very accurately (whole accuracy; 96.4%). Conclusions: Our novel breath test is a useful tool for identifying ALDH2*2 carriers, who are at high risk for esophageal and head and neck cancers. PMID:28594397

  5. AAV Gene Therapy for Alcoholism: Inhibition of Mitochondrial Aldehyde Dehydrogenase Enzyme Expression in Hepatoma Cells.

    PubMed

    Sanchez, Anamaria C; Li, Chengwen; Andrews, Barbara; Asenjo, Juan A; Samulski, R Jude

    2017-09-01

    Most ethanol is broken down in the liver in two steps by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) enzymes, which metabolize down ethanol into acetaldehyde and then acetate. Some individuals from the Asian population who carry a mutation in the aldehyde dehydrogenase gene (ALDH2*2) cannot metabolize acetaldehyde as efficiently, producing strong effects, including facial flushing, dizziness, hypotension, and palpitations. This results in an aversion to alcohol intake and protection against alcoholism. The large prevalence of this mutation in the human population strongly suggests that modulation of ALDH2 expression by genetic technologies could result in a similar phenotype. scAAV2 vectors encoding ALDH2 small hairpin RNA (shRNA) were utilized to validate this hypothesis by silencing ALDH2 gene expression in human cell lines. Human cell lines HEK-293 and HepG2 were transduced with scAAV2/shRNA, showing a reduction in ALDH2 RNA and protein expression with the two viral concentration assayed (1 × 10 4 and 1 × 10 5 vg/cell) at two different time points. In both cell lines, ALDH2 RNA levels were reduced by 90% and protein expression was inhibited by 90% and 52%, respectively, 5 days post infection. Transduced HepG2 VL17A cells (ADH+) exposed to ethanol resulted in a 50% increase in acetaldehyde levels. These results suggest that gene therapy could be a useful tool for the treatment of alcoholism by knocking down ALDH2 expression using shRNA technology delivered by AAV vectors.

  6. The Metabolic Status Drives Acclimation of Iron Deficiency Responses in Chlamydomonas reinhardtii as Revealed by Proteomics Based Hierarchical Clustering and Reverse Genetics*

    PubMed Central

    Höhner, Ricarda; Barth, Johannes; Magneschi, Leonardo; Jaeger, Daniel; Niehues, Anna; Bald, Till; Grossman, Arthur; Fufezan, Christian; Hippler, Michael

    2013-01-01

    Iron is a crucial cofactor in numerous redox-active proteins operating in bioenergetic pathways including respiration and photosynthesis. Cellular iron management is essential to sustain sufficient energy production and minimize oxidative stress. To produce energy for cell growth, the green alga Chlamydomonas reinhardtii possesses the metabolic flexibility to use light and/or carbon sources such as acetate. To investigate the interplay between the iron-deficiency response and growth requirements under distinct trophic conditions, we took a quantitative proteomics approach coupled to innovative hierarchical clustering using different “distance-linkage combinations” and random noise injection. Protein co-expression analyses of the combined data sets revealed insights into cellular responses governing acclimation to iron deprivation and regulation associated with photosynthesis dependent growth. Photoautotrophic growth requirements as well as the iron deficiency induced specific metabolic enzymes and stress related proteins, and yet differences in the set of induced enzymes, proteases, and redox-related polypeptides were evident, implying the establishment of distinct response networks under the different conditions. Moreover, our data clearly support the notion that the iron deficiency response includes a hierarchy for iron allocation within organelles in C. reinhardtii. Importantly, deletion of a bifunctional alcohol and acetaldehyde dehydrogenase (ADH1), which is induced under low iron based on the proteomic data, attenuates the remodeling of the photosynthetic machinery in response to iron deficiency, and at the same time stimulates expression of stress-related proteins such as NDA2, LHCSR3, and PGRL1. This finding provides evidence that the coordinated regulation of bioenergetics pathways and iron deficiency response is sensitive to the cellular and chloroplast metabolic and/or redox status, consistent with systems approach data. PMID:23820728

  7. Evidence of Circadian Rhythm, Oxygen Regulation Capacity, Metabolic Repeatability and Positive Correlations between Forced and Spontaneous Maximal Metabolic Rates in Lake Sturgeon Acipenser fulvescens

    PubMed Central

    Svendsen, Jon C.; Genz, Janet; Anderson, W. Gary; Stol, Jennifer A.; Watkinson, Douglas A.; Enders, Eva C.

    2014-01-01

    Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons). Using juvenile lake sturgeon (Acipenser fulvescens), the objective of this study was to test four hypotheses: 1) A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2) A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3) measurements of forced maximum metabolic rate (MMRF) are repeatable in individual fish; and 4) MMRF correlates positively with spontaneous maximum metabolic rate (MMRS). Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMRF. Trials lasting 24 h were used to measure standard metabolic rate (SMR) and MMRS. Repeatability and correlations between MMRF and MMRS were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O2sat)), demonstrating oxygen regulation. In contrast, MMRF was affected by hypoxia and decreased across the range from 100% O2sat to 70% O2sat. MMRF was repeatable in individual fish, and MMRF correlated positively with MMRS, but the relationships between MMRF and MMRS were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor). Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMRF and MMRS support the conjecture that MMRF represents a measure of organism performance that could be a target of natural selection. PMID:24718688

  8. Periphyton metabolism: A chamber approach

    NASA Astrophysics Data System (ADS)

    Brock, James T.; Royer, Todd V.; Snyder, Eric B.; Thomas, Steven A.

    In lotic ecosystems, the metabolism of periphyton is influenced strongly by natural and anthropogenic disturbances such as floods. Using recirculating metabolism chambers, we measured the metabolic activity of the Cladophora glomerata-dominated periphyton community in the Glen Canyon Dam tailwater, in relation to the 1996 controlled flood. Because scouring removes senescent plant material and detritus from periphyton, we hypothesized that productivity rates and the gross productivity/respiration (P/R) ratio of the periphyton community would be greater after the flood. Gross and net primary production (as chlorophyll-a) increased significantly after the flood and an approximately 2-fold increase was observed in net daily metabolism. Mean P/R ratio increased significantly from 1.3 in the pre-flood community to 2.6 in the post-flood community. Following the flood, periphyton on the rocks exhibited increased photosynthetic efficiency relative to measurements made before the flood. Given the importance of primary producers in desert rivers, such changes have implications for ecologically sound management of the Colorado and other rivers.

  9. Waterborne Zn influenced Zn uptake and lipid metabolism in two intestinal regions of juvenile goby Synechogobius hasta.

    PubMed

    Ling, Shi-Cheng; Luo, Zhi; Chen, Guang-Hui; Zhang, Dian-Guang; Liu, Xu

    2018-02-01

    The present study explored the influence of Zn addition in the water on Zn transport and lipid metabolism of two intestinal regions in goby Synechogobius hasta. Zn contents in water were 0.004 (control), 0.181 and 0.361mg Zn L -1 , respectively. The experiment lasted for 28 days. TG and Zn contents, mRNA contents of genes of Zn transport and lipid metabolism, and enzyme activity from anterior and mid-intestine tissues were analyzed. In anterior intestine, Zn addition in the water increased Zn contents, and mRNA concentrations of ZIP4, ZIP5, ATGL, PPARα, ZNF202 and KLF7, decreased TG contents, 6PGD and G6PD activities, and mRNA contents of 6PGD, G6PD, FAS, PPARγ, ICDH and KLF4. In mid-intestine tissue, the highest Zn and TG contents were observed for 0.18mg Zn/l group, in parallel with the highest expressions of ZnT1, ZIP4, ZIP5, 6PGD, FAS, ICDH, PPARγ, PPARα, ZNF202, KLF4 and KLF7, and with the highest FAS, 6PGD and G6PD activities. Thus, in the anterior intestine, Zn addition increased lipolysis and decreased lipogenesis, and accordingly reduced TG content. However, the highest mid-intestinal TG content in 0.18mg Zn/l group was due to the up-regulated lipogenesis. Although lipolysis was also increased, the incremental lipid synthesis was enough to compensate for lipid degradation, which led TG accumulation. Our results, for the first time, show an anterior/mid functional regionalization of the intestine in lipid metabolism and Zn transport of S. hasta following Zn exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Maternal Exercise Improves the Metabolic Health of Adult Offspring.

    PubMed

    Harris, Johan E; Baer, Lisa A; Stanford, Kristin I

    2018-03-01

    The intrauterine environment can modulate the course of development and confer an enduring effect on offspring health. The effects of maternal diet to impair offspring metabolic health are well established, but the effects of maternal exercise on offspring metabolic health have been less defined. Because physical exercise is a treatment for obesity and type 2 diabetes (T2D), maternal exercise is an appealing intervention to positively influence the intrauterine environment and improve the metabolic health of offspring. Recent research has provided insights into the effects of maternal exercise on the metabolic health of adult offspring, which is the focus of this review. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Permeability and toxicity characteristics of L-cysteine and 2-methyl-thiazolidine-4-carboxylic acid in Caco-2 cells.

    PubMed

    Kartal-Hodzic, Alma; Marvola, Tuuli; Schmitt, Mechthild; Harju, Kirsi; Peltoniemi, Marikki; Sivén, Mia

    2013-01-01

    Acetaldehyde is a known mutagenic substance and has been classified as a group-one carcinogen by the WHO. It is possible to bind acetaldehyde locally in the gastrointestinal (GI) tract with the semi-essential amino acid l-cysteine, which reacts covalently with acetaldehyde and forms compound 2-methyl-thiozolidine-4-carboxylic acid (MTCA). The Caco-2 cell line was used to determine the permeation of l-cysteine and MTCA, as well as the possible cell toxicity of both substances. Neither of the substances permeated through the Caco-2 cells at the concentrations used in this study, and only the highest concentration of MTCA affected the viability of the cells in the MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) test. These results showed that when l-cysteine is administered in formulations releasing it locally in the lower parts of GI tract, it is not absorbed but can react with acetaldehyde, and that neither l-cysteine nor MTCA is harmful to the cells when present locally in the upper parts of GI tract. This study also shows that MTCA is sensitive at a lower pH of 5.5. Since stable MTCA is desired in different parts of the GI tract, this observation raises concern over the influence of lower pH on l-cysteine-containing product ability to bind and eliminate carcinogenic acetaldehyde.

  12. Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions

    PubMed Central

    He, Tianliang; Li, Hongyun

    2017-01-01

    ABSTRACT Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. PMID:28698277

  13. Influences of thermal environment on fish growth.

    PubMed

    Boltaña, Sebastián; Sanhueza, Nataly; Aguilar, Andrea; Gallardo-Escarate, Cristian; Arriagada, Gabriel; Valdes, Juan Antonio; Soto, Doris; Quiñones, Renato A

    2017-09-01

    Thermoregulation in ectothermic animals is influenced by the ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown whether physiological and/or metabolic traits are impacted by modifications to the thermal environment. Our research provides key evidence that fish ectotherms are highly influenced by thermal variability during development, which leads to important modifications at several metabolic levels (e.g., growth trajectories, microstructural alterations, muscle injuries, and molecular mechanisms). In Atlantic salmon ( Salmo salar ), a wide thermal range (Δ T 6.4°C) during development (posthatch larvae to juveniles) was associated with increases in key thermal performance measures for survival and growth trajectory. Other metabolic traits were also significantly influenced, such as size, muscle cellularity, and molecular growth regulators possibly affected by adaptive processes. In contrast, a restricted thermal range (Δ T 1.4°C) was detrimental to growth, survival, and cellular microstructure as muscle growth could not keep pace with increased metabolic demands. These findings provide a possible basic explanation for the effects of thermal environment during growth. In conclusion, our results highlight the key role of thermal range amplitude on survival and on interactions with major metabolism-regulating processes that have positive adaptive effects for organisms.

  14. Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.

    PubMed

    Altuna, María Eugenia; Lelli, Sandra Marcela; San Martín de Viale, Leonor C; Damasco, María Cristina

    2006-10-01

    Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.

  15. Carbon metabolism of peach fruit after harvest: changes in enzymes involved in organic acid and sugar level modifications.

    PubMed

    Borsani, Julia; Budde, Claudio O; Porrini, Lucía; Lauxmann, Martin A; Lombardo, Verónica A; Murray, Ricardo; Andreo, Carlos S; Drincovich, María F; Lara, María V

    2009-01-01

    Peach (Prunus persica L. Batsch) is a climacteric fruit that ripens after harvest, prior to human consumption. Organic acids and soluble sugars contribute to the overall organoleptic quality of fresh peach; thus, the integrated study of the metabolic pathways controlling the levels of these compounds is of great relevance. Therefore, in this work, several metabolites and enzymes involved in carbon metabolism were analysed during the post-harvest ripening of peach fruit cv 'Dixiland'. Depending on the enzyme studied, activity, protein level by western blot, or transcript level by quantitative real time-PCR were analysed. Even though sorbitol did not accumulate at a high level in relation to sucrose at harvest, it was rapidly consumed once the fruit was separated from the tree. During the ripening process, sucrose degradation was accompanied by an increase of glucose and fructose. Specific transcripts encoding neutral invertases (NIs) were up-regulated or down-regulated, indicating differential functions for each putative NI isoform. Phosphoenolpyruvate carboxylase was markedly induced, and may participate as a glycolytic shunt, since the malate level did not increase during post-harvest ripening. The fermentative pathway was highly induced, with increases in both the acetaldehyde level and the enzymes involved in this process. In addition, proteins differentially expressed during the post-harvest ripening process were also analysed. Overall, the present study identified enzymes and pathways operating during the post-harvest ripening of peach fruit, which may contribute to further identification of varieties with altered levels of enzymes/metabolites or in the evaluation of post-harvest treatments to produce fruit of better organoleptic attributes.

  16. Kynurenine pathway metabolism and the microbiota-gut-brain axis.

    PubMed

    Kennedy, P J; Cryan, J F; Dinan, T G; Clarke, G

    2017-01-01

    It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Inter-regional comparison of land-use effects on stream metabolism

    Treesearch

    Melody J. Bernot; Daniel J. Sobota; Robert O. Hall; Patrick J. Mulholland; Walter K. Dodds; Jackson R. Webster; Jennifer L. Tank; Linda R. Ashkenas; Lee W. Cooper; Clifford N. Dahm; Stanley V. Gregory; Nancy B. Grimm; Stephen K. Hamilton; Sherri L. Johnson; William H. McDowell; Judith L. Meyer; Bruce Peterson; Geoffrey C. Poole; H. Maurice Valett; Clay Arango; Jake J. Beaulieu; Amy J. Burgin; Chelsea Crenshaw; Ashley M. Helton; Laura Johnson; Jeff Merriam; B.R. Niederlehner; Jonathan M. O' Brien; Jody D. Potter; Richard W. Sheibley; Suzanne M. Thomas; Kym Wilson

    2010-01-01

    Rates of whole-system metabolism (production and respiration) are fundamental indicators of ecosystem structure and function. Although first-order, proximal controls are well understood, assessments of the interactions between proximal controls and distal controls, such as land use and geographic region, are lacking. Thus, the influence of land use on stream metabolism...

  18. Influence of the 48867A>C (Asp358Ala) IL6R polymorphism on response to a lifestyle modification intervention in individuals with metabolic syndrome.

    PubMed

    Vargas, V R A; Bonatto, S L; Macagnan, F E; Feoli, A M P; Alho, C S; Santos, N D V; Schmitt, V M

    2013-02-28

    We evaluated the response of individuals with metabolic syndrome to lifestyle modification intervention and examined the influence of the 48867A>C (Asp358Ala) IL6R (rs2228145) polymorphism on this response. Participants were randomly divided into two groups: NI, nutritional intervention; NIE, nutritional intervention and exercise practice. Intervention lasted three months and participants completed a comprehensive evaluation and had blood collected for biochemical measurements. Eighty-two sedentary individuals with at least three criteria for metabolic syndrome were included. Comparing metabolic syndrome parameters before and after intervention, a reduction of waist circumference was observed, although significant only for AA and AC genotypes. Also, a decrease in triglyceride levels was observed (significant for AA genotype individuals; for the AC genotype, only in the NIE group). Significant reduction of fasting glucose level was observed in all AA genotype individuals; for the AC genotype, only in the NI group. Systolic blood pressure showed significant reduction in AA and AC genotype individuals. After three months of lifestyle modification intervention, improvement in some of the metabolic syndrome parameters was observed, some associated with the IL6R genotype. At enrollment, participants with genotypes AA and AC showed more severe conditions regarding metabolic syndrome inclusion criteria, supporting previous reports that the A allele is a genetic risk factor. These individuals, however, had a better response to intervention compared to individuals with the CC genotype, suggesting that nutritional control and exercise practice could prevent risks associated with metabolic syndrome more efficiently in individuals bearing the A allele.

  19. Weight classification does not influence the short-term endocrine or metabolic effects of high-fructose corn syrup-sweetened beverages.

    PubMed

    Heden, Timothy D; Liu, Ying; Kearney, Monica L; Kanaley, Jill A

    2014-05-01

    Obesity and high-fructose corn syrup (HFCS)-sweetened beverages are associated with an increased risk of chronic disease, but it is not clear whether obese (Ob) individuals are more susceptible to the detrimental effects of HFCS-sweetened beverages. The purpose of this study was to examine the endocrine and metabolic effects of consuming HFCS-sweetened beverages, and whether weight classification (normal weight (NW) vs. Ob) influences these effects. Ten NW and 10 Ob men and women who habitually consumed ≤355 mL per day of sugar-sweetened beverages were included in this study. Initially, the participants underwent a 4-h mixed-meal test after a 12-h overnight fast to assess insulin sensitivity, pancreatic and gut endocrine responses, insulin secretion and clearance, and glucose, triacylglycerol, and cholesterol responses. Next, the participants consumed their normal diet ad libitum, with 1065 mL per day (117 g·day(-1)) of HFCS-sweetened beverages added for 2 weeks. After the intervention, the participants repeated the mixed-meal test. HFCS-sweetened beverages did not significantly alter body weight, insulin sensitivity, insulin secretion or clearance, or endocrine, glucose, lipid, or cholesterol responses in either NW or Ob individuals. Regardless of previous diet, Ob individuals, compared with NW individuals, had ∼28% lower physical activity levels, 6%-9% lower insulin sensitivity, 12%-16% lower fasting high-density-lipoprotein cholesterol concentrations, 84%-144% greater postprandial triacylglycerol concentrations, and 46%-79% greater postprandial insulin concentrations. Greater insulin responses were associated with reduced insulin clearance, and there were no differences in insulin secretion. These findings suggest that weight classification does not influence the short-term endocrine and metabolic effects of HFCS-sweetened beverages.

  20. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    NASA Technical Reports Server (NTRS)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  1. Tracking Polymicrobial Metabolism in Cystic Fibrosis Airways: Pseudomonas aeruginosa Metabolism and Physiology Are Influenced by Rothia mucilaginosa-Derived Metabolites.

    PubMed

    Gao, Bei; Gallagher, Tara; Zhang, Ying; Elbadawi-Sidhu, Mona; Lai, Zijuan; Fiehn, Oliver; Whiteson, Katrine L

    2018-04-25

    Due to a lack of effective immune clearance, the airways of cystic fibrosis patients are colonized by polymicrobial communities. One of the most widespread and destructive opportunistic pathogens is Pseudomonas aeruginosa ; however, P. aeruginosa does not colonize the airways alone. Microbes that are common in the oral cavity, such as Rothia mucilaginosa , are also present in cystic fibrosis patient sputum and have metabolic capacities different from those of P. aeruginosa Here we examine the metabolic interactions of P. aeruginosa and R. mucilaginosa using stable-isotope-assisted metabolomics. Glucose-derived 13 C was incorporated into glycolysis metabolites, namely, lactate and acetate, and some amino acids in R. mucilaginosa grown aerobically and anaerobically. The amino acid glutamate was unlabeled in the R. mucilaginosa supernatant but incorporated the 13 C label after P. aeruginosa was cross-fed the R. mucilaginosa supernatant in minimal medium and artificial-sputum medium. We provide evidence that P. aeruginosa utilizes R. mucilaginosa -produced metabolites as precursors for generation of primary metabolites, including glutamate. IMPORTANCE Pseudomonas aeruginosa is a dominant and persistent cystic fibrosis pathogen. Although P. aeruginosa is accompanied by other microbes in the airways of cystic fibrosis patients, few cystic fibrosis studies show how P. aeruginosa is affected by the metabolism of other bacteria. Here, we demonstrate that P. aeruginosa generates primary metabolites using substrates produced by another microbe that is prevalent in the airways of cystic fibrosis patients, Rothia mucilaginosa These results indicate that P. aeruginosa may get a metabolic boost from its microbial neighbor, which might contribute to its pathogenesis in the airways of cystic fibrosis patients.

  2. Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial.

    PubMed

    Gomez-Delgado, Francisco; Alcala-Diaz, Juan Francisco; Garcia-Rios, Antonio; Delgado-Lista, Javier; Ortiz-Morales, Ana; Rangel-Zuñiga, Oriol; Tinahones, Francisco Jose; Gonzalez-Guardia, Lorena; Malagon, Maria M; Bellido-Muñoz, Enrique; Ordovas, Jose M; Perez-Jimenez, Francisco; Lopez-Miranda, Jose; Perez-Martinez, Pablo

    2014-07-01

    To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene-diet interactions were observed in either diet. These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Glutamine Metabolism in Cancer: Understanding the Heterogeneity

    PubMed Central

    Cluntun, Ahmad A; Lukey, Michael J; Cerione, Richard A; Locasale, Jason W

    2017-01-01

    Reliance on glutamine has long been considered a hallmark of cancer cell metabolism. However, some recent studies have challenged this notion in vivo, prompting a need for further clarifications on the role of glutamine metabolism in cancer. We find that there is ample evidence of an essential role for glutamine in tumors and that a variety of factors, including tissue type, the underlying cancer genetics, the tumor microenvironment and other variables such as diet and host physiology collectively influence the role of glutamine in cancer. Thus the requirements for glutamine in cancer are overall highly heterogeneous. In this review, we discuss the implications both for basic science and for targeting glutamine metabolism in cancer therapy. PMID:28393116

  4. Metabolic syndrome and cardiometabolic risk in PCOS.

    PubMed

    Cussons, Andrea J; Stuckey, Bronwyn G A; Watts, Gerald F

    2007-02-01

    The cardiovascular risk associated with the polycystic ovary syndrome (PCOS) has recently attracted much interest. Women with PCOS are more likely to fulfill the diagnosis of the metabolic syndrome, a cluster of related cardiometabolic factors known to predict long-term risk of cardiovascular disease and type 2 diabetes. We review the literature pertaining to the link between the metabolic syndrome, cardiovascular disease, and PCOS. We focus on the influence of obesity and hyperandrogenemia, and on strategies for identifying cardiovascular risk in PCOS.

  5. [The influence of alcohol on the oral cavity, salivary glands and saliva].

    PubMed

    Waszkiewicz, Napoleon; Zalewska, Anna; Szulc, Agata; Kepka, Alina; Konarzewska, Beata; Zalewska-Szajda, Beata; Chojnowska, Sylwia; Waszkiel, Danuta; Zwierz, Krzysztof

    2011-01-01

    Ethanol diffuses rapidly into saliva during the drinking, and immediately after its salivary concentration is temporarily much higher than in plasma. Within 30 minutes, salivary ethanol concentration equilibrates with the plasma level, thus suggesting that ethanol easily penetrates the whole body, including oral cavity tissues and salivary glands. After alcohol intake, the level of acetaldehyde in saliva strikingly exceeds the level in systemic blood. From saliva, acetaldehyde and ethanol easily reach all local tissues. Damage to the oral tissues seems to be ascribed mostly to the action of acetaldehyde, although some acute effects depend on a direct action of ethanol and formation of reactive oxygen species (ROS) and fatty acid ethyl esters (FAEEs). It is known that the oral mucosal surface is the home of numerous normal flora microorganisms and is the portal of entry for the majority of pathogens. The oral cavity and salivary antimicrobial immune defense systems eliminate pathogens and prevent massive overgrowth of microorganisms. An oral defense system participate in the protection of not only oral tissues, but also in the protection of upper digestive and respiratory tracts, against a number of microbial pathogens. Saliva plays the role in the oral cavity lubrication, maintenance of mucosal and tooth integrity, esophageal physiology, digestion and gastric cytoprotection. As alcohol abuse affects the structure and function of oral cavity mucosa, salivary glands and saliva, the maintenance of oral and general health under normal conditions is seriously impaired during the drinking. The severe tissue damage occurs in particular when alcohol abuse coincides with smoking.

  6. Acute nutritional ketosis: implications for exercise performance and metabolism

    PubMed Central

    2014-01-01

    Ketone bodies acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB) may provide an alternative carbon source to fuel exercise when delivered acutely in nutritional form. The metabolic actions of ketone bodies are based on sound evolutionary principles to prolong survival during caloric deprivation. By harnessing the potential of these metabolic actions during exercise, athletic performance could be influenced, providing a useful model for the application of ketosis in therapeutic conditions. This article examines the energetic implications of ketone body utilisation with particular reference to exercise metabolism and substrate energetics. PMID:25379174

  7. Leptin influences estrogen metabolism and accelerates prostate cell proliferation.

    PubMed

    Habib, Christine N; Al-Abd, Ahmed M; Tolba, Mai F; Khalifa, Amani E; Khedr, Alaa; Mosli, Hisham A; Abdel-Naim, Ashraf B

    2015-01-15

    The present study was designed to investigate the effect of leptin on estrogen metabolism in prostatic cells. Malignant (PC-3) and benign (BPH-1) human prostate cells were treated with 17-β-hydroxyestradiol (1 μM) alone or in combination with leptin (0.4, 4, 40 ng/ml) for 72 h. Cell proliferation assay, immunocytochemical staining of estrogen receptor (ER), liquid chromatography-tandem mass spectrometry method (LC-MS) and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were used. Cell proliferation assay demonstrated that leptin caused significant growth potentiation in both cells. Immunocytochemical staining showed that leptin significantly increased the expression of ER-α and decreased that of ER-β in PC-3 cells. LC-MS method revealed that leptin increased the concentration 4-hydroxyestrone and/or decreased that of 2-methoxyestradiol, 4-methoxyestradiol and 2-methoxyestrone. Interestingly, RT-PCR showed that leptin significantly up-regulated the expression of aromatase and cytochrome P450 1B1 (CYP1B1) enzymes; however down-regulated the expression of catechol-o-methyltransferase (COMT) enzyme. These data indicate that leptin-induced proliferative effect in prostate cells might be partly attributed to estrogen metabolism. Thus, leptin might be a novel target for therapeutic intervention in prostatic disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Influence of cimetidine and diethyldithiocarbamate on the metabolism of halothane and methoxyflurane in vitro.

    PubMed

    Loesch, J; Siegers, C P; Younes, M

    1987-06-01

    The metabolism of halothane and methoxyflurane was measured in vitro by the vial equilibration method using the S-9-fraction from rat liver as source of enzymes. Kinetic values were measured for halothane: Vmax = 11.6 nmol/g.min, KM = 19.6 mumol/l and methoxyflurane: Vmax = 12.0 nmol/g.min, KM = 17.5 mumol/l. Dithiocarb showed strong inhibitory activity on halothane and methoxyflurane metabolism; inhibition constants were calculated as Ki = 0.051 mmol/l and Ki = 0.004 mmol/l, respectively. Cimetidine inhibited the metabolism of both anesthetics to a lesser extent. Inhibition constants were calculated as Ki = 16.2 mmol/l and Ki = 8.2 mmol/l for halothane and methoxyflurane, respectively. The observed inhibitory properties of dithiocarb and cimetidine on the metabolism of halothane and methoxyflurane may be of interest in connection with the problem of toxic liver and kidney injury after anesthesia with these agents.

  9. Role and mechanism of the AMPK pathway in waterborne Zn exposure influencing the hepatic energy metabolism of Synechogobius hasta

    NASA Astrophysics Data System (ADS)

    Wu, Kun; Huang, Chao; Shi, Xi; Chen, Feng; Xu, Yi-Huan; Pan, Ya-Xiong; Luo, Zhi; Liu, Xu

    2016-12-01

    Previous studies have investigated the physiological responses in the liver of Synechogobius hasta exposed to waterborne zinc (Zn). However, at present, very little is known about the underlying molecular mechanisms of these responses. In this study, RNA sequencing (RNA-seq) was performed to analyse the differences in the hepatic transcriptomes between control and Zn-exposed S. hasta. A total of 36,339 unigenes and 1,615 bp of unigene N50 were detected. These genes were further annotated to the Nonredundant protein (NR), Nonredundant nucleotide (Nt), Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG) and Gene Ontology (GO) databases. After 60 days of Zn exposure, 708 and 237 genes were significantly up- and down-regulated, respectively. Many differentially expressed genes (DEGs) involved in energy metabolic pathways were identified, and their expression profiles suggested increased catabolic processes and reduced biosynthetic processes. These changes indicated that waterborne Zn exposure increased the energy production and requirement, which was related to the activation of the AMPK signalling pathway. Furthermore, using the primary hepatocytes of S. hasta, we identified the role of the AMPK signalling pathway in Zn-influenced energy metabolism.

  10. Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The “Study of Origin”

    PubMed Central

    Ruiz-Núñez, Begoña; Raison, Charles L.; Muskiet, Frits A. J.

    2016-01-01

    Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with “ancient mild stress factors,” including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders. PMID:27366752

  11. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influence metabolic responses in post-weaned Holstein calves challenged with bovine herpesvirus-1 and Mannheimia haemolytica

    USDA-ARS?s Scientific Manuscript database

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences metabolic responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose of M...

  12. The scaling and temperature dependence of vertebrate metabolism

    PubMed Central

    White, Craig R; Phillips, Nicole F; Seymour, Roger S

    2005-01-01

    Body size and temperature are primary determinants of metabolic rate, and the standard metabolic rate (SMR) of animals ranging in size from unicells to mammals has been thought to be proportional to body mass (M) raised to the power of three-quarters for over 40 years. However, recent evidence from rigorously selected datasets suggests that this is not the case for birds and mammals. To determine whether the influence of body mass on the metabolic rate of vertebrates is indeed universal, we compiled SMR measurements for 938 species spanning six orders of magnitude variation in mass. When normalized to a common temperature of 38 °C, the SMR scaling exponents of fish, amphibians, reptiles, birds and mammals are significantly heterogeneous. This suggests both that there is no universal metabolic allometry and that models that attempt to explain only quarter-power scaling of metabolic rate are unlikely to succeed. PMID:17148344

  13. Omics Approaches To Probe Microbiota and Drug Metabolism Interactions.

    PubMed

    Nichols, Robert G; Hume, Nicole E; Smith, Philip B; Peters, Jeffrey M; Patterson, Andrew D

    2016-12-19

    The drug metabolism field has long recognized the beneficial and sometimes deleterious influence of microbiota in the absorption, distribution, metabolism, and excretion of drugs. Early pioneering work with the sulfanilamide precursor prontosil pointed toward the necessity not only to better understand the metabolic capabilities of the microbiota but also, importantly, to identify the specific microbiota involved in the generation and metabolism of drugs. However, technological limitations important for cataloging the microbiota community as well as for understanding and/or predicting their metabolic capabilities hindered progress. Current advances including mass spectrometry-based metabolite profiling as well as culture-independent sequence-based identification and functional analysis of microbiota have begun to shed light on microbial metabolism. In this review, case studies will be presented to highlight key aspects (e.g., microbiota identification, metabolic function and prediction, metabolite identification, and profiling) that have helped to clarify how the microbiota might impact or be impacted by drug metabolism. Lastly, a perspective of the future of this field is presented that takes into account what important knowledge is lacking and how to tackle these problems.

  14. The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol.

    PubMed

    Grønhøj Larsen, F; Jakobsen, P; Grønhøj Larsen, C; Heidenheim, M; Held, E; Nielsen-Kudsk, F

    2009-09-01

    Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life. To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined. Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography. Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies. The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing

  15. Influence of a flooding dose of valine on key indicators of metabolic status in the growing pig.

    PubMed

    Libao-Mercado, A J; Columbus, D; de Lange, C F M

    2015-02-01

    A key concern with the flooding dose technique for measuring protein synthesis is that a large dose of amino acid (AA) can potentially change the animals' hormonal and nutritional status, which in turn can influence protein synthesis. Among stable isotope tracers, 1-[(13)C]-valine is the preferred AA for measuring protein synthesis in gut tissue and mucins. A study was conducted to determine the impact of a flooding dose of valine on the metabolic status of pigs. Six barrows [16.5 kg body weight (BW)] were randomly assigned to intravenous infusions of either 150 mM valine (1.5 mmol/kg BW) or physiological saline, following a crossover design. Blood samples were taken 10 min prior to infusion, at the end of infusion, at 10-min intervals for 60 min post-infusion, and at 90 and 120 min post-infusion. Plasma concentrations of insulin, glucose, AA, urea nitrogen and packed cell volume (PCV) were measured. Infusion of valine increased plasma valine concentrations (4129 vs. 582 μM; P < 0.05) but had no influence on PCV (26.4% vs. 27.2%) and plasma concentrations of glucose (6.0 vs. 5.8 mM) and insulin (8.2 vs. 8.5 μU/ml; P > 0.10). Plasma urea nitrogen concentration was reduced with valine infusion (8.5 vs. 7.8 mg/dl; P < 0.05). A flooding dose of valine had no impact on plasma concentrations of AA, and specifically branched-chain AA such as leucine (240 vs. 231 μM) and isoleucine (310 vs. 331 μM; P > 0.10). There was, however, a slight increase in the plasma concentrations of threonine (224 vs. 263 μM; P < 0.05) and a tendency towards reduced glycine (1387 vs. 1313 μM; P < 0.10). The results indicate that a flooding dose of valine does not cause a substantial change in the metabolic status of growing pigs and is therefore suitable for measuring protein synthesis rates. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  16. Metabolic syndrome and its characteristics among obese patients attending an obesity clinic.

    PubMed

    Termizy, H M; Mafauzy, M

    2009-04-01

    The increased prevalence of metabolic syndrome worldwide is closely related to the rising obesity epidemic. The objectives of the study were to determine the prevalence and identify the associated and prognostic factors that influence the risk of metabolic syndrome among obese patients attending the Obesity Clinic at Hospital Universiti Sains Malaysia. A study was conducted involving 102 obese persons who attended the Obesity Clinic from January 1 to December 31, 2005. Metabolic syndrome was defined according to the International Diabetes Federation criteria. The overall prevalence of metabolic syndrome among obese patients was 40.2 percent. The prevalence was higher in females (43.7 percent) than in males (32.3 percent). The prevalence of metabolic syndrome was noted to increase with increasing body mass index class, from class 1 to class 2. However, the prevalence was lower in obesity class 3. The prevalence of metabolic comorbidities of raised blood pressure, reduced high density lipoprotein, high triglyceride and raised fasting blood glucose was 42, 40, 36 and 17 percent, respectively. A quarter of obese patients in this study had no other comorbidity. Based on logistic regression multivariable analysis, age was the only significant associated factor that influenced the risk of having metabolic syndrome. The prevalence of metabolic syndrome was high and the highest comorbidity was high blood pressure. Age was the only significant risk factor of having this syndrome.

  17. Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

    PubMed

    Sharma, Vineeta; Forte, Trudy M; Ryan, Robert O

    2013-04-01

    Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.

  18. Ovine placental steroid synthesis and metabolism in late gestation.

    PubMed

    Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

    2018-04-14

    Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

  19. The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

    PubMed Central

    Jahan-Mihan, Alireza; Rodriguez, Judith; Christie, Catherine; Sadeghi, Marjan; Zerbe, Tara

    2015-01-01

    The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring. PMID:26561832

  20. Comparing the impact of ultrafine particles from petrodiesel and biodiesel combustion to bacterial metabolism by targeted HPLC-MS/MS metabolic profiling.

    PubMed

    Zhong, Fanyi; Xu, Mengyang; Schelli, Katie; Rutowski, Joshua; Holmén, Britt A; Zhu, Jiangjiang

    2017-08-01

    Alterations of gut bacterial metabolism play an important role in their host metabolism, and can result in diseases such as obesity and diabetes. While many factors were discovered influencing the gut bacterial metabolism, exposure to ultrafine particles (UFPs) from engine combustions were recently proposed to be a potential risk factor for the perturbation of gut bacterial metabolism, and consequentially to obesity and diabetes development. This study focused on evaluation of how UFPs from diesel engine combustions impact gut bacterial metabolism. We hypothesize that UFPs from different type of diesel (petrodiesel vs. biodiesel) will both impact bacterial metabolism, and the degree of impact is also diesel type-dependent. Targeted metabolic profiling of 221 metabolites were applied to three model gut bacteria in vitro, Streptococcus salivarius, Lactobacillus acidophilus and Lactobacillus fermentum. UFPs from two types of fuels, petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume), were exposed to the bacteria and their metabolic changes were compared. For each bacterial strain, metabolites with significantly changed abundance were observed in both perturbations, and all three strains have increased number of altered metabolites detected from B20 UFPs perturbation in comparison to B0 UFPs. Multivariate statistical analysis further confirmed that the metabolic profiles were clearly different between testing groups. Metabolic pathway analyses also demonstrated several important metabolic pathways, including pathways involves amino acids biosynthesis and sugar metabolism, were significantly impacted by UFPs exposure. Copyright © 2017 Elsevier Inc. All rights reserved.