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Sample records for acid metabolism conclusions

  1. Amino Acid Metabolism Disorders

    MedlinePlus

    ... breaks the food parts down into sugars and acids, your body's fuel. Your body can use this ... process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple ...

  2. Ten-year study on acid precipitation nears conclusion

    SciTech Connect

    Olem, H. )

    1990-04-01

    Results from the National Acid Precipitation Assessment Program (NAPAP) are discussed. Final results are contained in 26 state of the science reports. Seven of the reports provide information on acid rain and aquatic ecosystems. They describe the current state of acidic surface waters, watershed processes affecting surface water chemistry, historical evidence for surface water acidification, methods for forecasting future changes, and the response of acidic surface water to liming. Six areas of the country were found to be of special interest: southwest Adirondacks, New England, forested areas of the mid-Atlantic highlands, the Atlantic coastal plain, the northern Florida highlands, parts of northeastern Wisconsin and the Upper Peninsula of Michigan. Environmental effects, mitigation efforts and possible legislation are briefly discussed.

  3. Amino Acid Metabolism Disorders

    MedlinePlus

    ... acidemia? In ASA, the body can’t remove ammonia or a substance called argininosuccinic acid from the ... and children include: Breathing problems High levels of ammonia in the bloodIntense headache, especially after a high- ...

  4. Treatment of Amino Acid Metabolism Disorders

    MedlinePlus

    ... amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please fill ... This is an amino acid that helps remove ammonia from the blood. Babies with HCY may need ...

  5. CACODYLIC ACID (DMAV): METABOLISM AND ...

    EPA Pesticide Factsheets

    The cacodylic acid (DMAV) issue paper discusses the metabolism and pharmacokinetics of the various arsenical chemicals; evaluates the appropriate dataset to quantify the potential cancer risk to the organic arsenical herbicides; provides an evaluation of the mode of carcinogenic action (MOA) for DMAV including a consideration of the key events for bladder tumor formation in rats, other potential modes of action; and also considers the human relevance of the proposed animal MOA. As part of tolerance reassessment under the Food Quality Protection Act for the August 3, 2006 deadline, the hazard of cacodylic acid is being reassessed.

  6. 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

  7. Intestinal metabolism of sulfur amino acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gastrointestinal tract (GIT) is a metabolically significant site of sulfur amino acid (SAA) metabolism in the body and metabolizes approx. 20% of the dietary methionine intake that is mainly transmethylated to homocysteine and transsulfurated to cysteine. The GIT accounts for approx. 25% of the ...

  8. Biosynthesis and metabolism of salicylic acid.

    PubMed Central

    Lee, H I; León, J; Raskin, I

    1995-01-01

    Pathways of salicylic acid (SA) biosynthesis and metabolism in tobacco have been recently identified. SA, an endogenous regulator of disease resistance, is a product of phenylpropanoid metabolism formed via decarboxylation of trans-cinnamic acid to benzoic acid and its subsequent 2-hydroxylation to SA. In tobacco mosaic virus-inoculated tobacco leaves, newly synthesized SA is rapidly metabolized to SA O-beta-D-glucoside and methyl salicylate. Two key enzymes involved in SA biosynthesis and metabolism: benzoic acid 2-hydroxylase, which converts benzoic acid to SA, and UDPglucose:SA glucosyltransferase (EC 2.4.1.35), which catalyzes conversion of SA to SA glucoside have been partially purified and characterized. Progress in enzymology and molecular biology of SA biosynthesis and metabolism will provide a better understanding of signal transduction pathway involved in plant disease resistance. PMID:11607533

  9. Biosynthesis and metabolism of salicylic acid

    SciTech Connect

    Lee, H.; Leon, J.; Raskin, I.

    1995-05-09

    Pathways of salicylic acid (SA) biosynthesis and metabolism in tobacco have been recently identified. SA, an endogenous regulator of disease resistance, is a product of phenylpropanoid metabolism formed via decarboxylation of trans-cinnamic acid to benzoic acid and its subsequent 2-hydroxylation to SA. In tobacco mosaic virus-inoculated tobacco leaves, newly synthesized SA is rapidly metabolized to SA O-{beta}-D-glucoside and methyl salicylate. Two key enzymes involved in SA biosynthesis and metabolism: benzoic acid 2-hydroxylase, which converts benzoic acid to SA, and UDPglucose:SA glucosyltransferase (EC 2.4.1.35), which catalyzes conversion of SA to SA glucoside have been partially purified and characterized. Progress in enzymology and molecular biology of SA biosynthesis and metabolism will provide a better understanding of signal transduction pathway involved in plant disease resistance. 62 refs., 1 fig.

  10. Citric Acid Metabolism in the Bovine Rumen

    PubMed Central

    Wright, D. E.

    1971-01-01

    Rumen microorganisms rapidly metabolize citric acid to carbon dioxide and acetic acid. The rate of metabolism varied between 0.00008 and 0.76 μmoles per g per min, the rate becoming higher as the citric acid concentration increased. The addition of potassium chloride to rumen contents decreased the rate of utilization. The results indicate that dietary citric acid is unlikely to accumulate in the rumen to a sufficiently high level to be an important factor in hypomagnesemia, except where other factors such as very high potassium levels in the food influence its metabolism. PMID:5549696

  11. Intestinal transport and metabolism of bile acids

    PubMed Central

    Dawson, Paul A.; Karpen, Saul J.

    2015-01-01

    In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

  12. Bile Acids, Obesity, and the Metabolic Syndrome

    PubMed Central

    Ma, Huijuan; Patti, Mary Elizabeth

    2014-01-01

    Bile acids are increasingly recognized as key regulators of systemic metabolism. While bile acids have long been known to play important and direct roles in nutrient absorption, bile acids also serve as signaling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycemic control. Thus, modulation of bile acid levels and signaling, using bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans. PMID:25194176

  13. Metabolism of hop-derived bitter acids.

    PubMed

    Cattoor, Ko; Dresel, Michael; De Bock, Lies; Boussery, Koen; Van Bocxlaer, Jan; Remon, Jean-Paul; De Keukeleire, Denis; Deforce, Dieter; Hofmann, Thomas; Heyerick, Arne

    2013-08-21

    In this study, in vitro metabolism of hop-derived bitter acids was investigated. Besides their well-known use as bitter compounds in beer, in several studies, bioactive properties have been related to these types of molecules. However, scientific data on the absorption, distribution, metabolism, and excretion aspects of these compounds are limited. More specific, in this study, α-acids, β-acids, and iso-α-acids were incubated with rabbit microsomes, and fractions were subjected to LC-MS/MS analysis for identification of oxidative biotransformation products. Metabolism of β-acids was mainly characterized by conversion into hulupones and the formation of a series of tricyclic oxygenated products. The most important metabolites of α-acids were identified as humulinones and hulupones. Iso-α-acids were found to be primarly metabolized into cis- and trans-humulinic acids, next to oxidized alloiso-α-acids. Interestingly, the phase I metabolites were highly similar to the oxidative degradation products in beer. These findings show a first insight into the metabolites of hop-derived bitter acids and could have important practical implications in the bioavailability aspects of these compounds, following ingestion of hop-based food products and nutraceuticals.

  14. 2-Hydroxy Acids in Plant Metabolism

    PubMed Central

    Maurino, Veronica G.; Engqvist, Martin K. M.

    2015-01-01

    Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in plant metabolism and physiology. In this chapter, we summarize the current knowledge about the metabolic pathways and cellular processes in which they are involved, focusing on the proteins that participate in their metabolism and cellular/intracellular transport in Arabidopsis. PMID:26380567

  15. Lipoic Acid Metabolism in Microbial Pathogens

    PubMed Central

    Spalding, Maroya D.; Prigge, Sean T.

    2010-01-01

    Summary: Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments. PMID:20508247

  16. Cellular Metabolism of Unnatural Sialic Acid Precursors

    PubMed Central

    Pham, Nam D.; Fermaintt, Charles S.; Rodriguez, Andrea C.; McCombs, Janet E.; Nischan, Nicole; Kohler, Jennifer J.

    2015-01-01

    Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight into carbohydrate biology and mechanisms has been aided by metabolic oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with novel functional groups are incorporated into cellular glycoconjugates and used to probe biological systems. While MOE has expanded knowledge of carbohydrate biology, limited metabolism of unnatural carbohydrate analogs restricts its use. Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid, and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that different cell lines can have different metabolic roadblocks in the synthesis of cell surface SiaDAz. These findings point to roles for promiscuous intracellular esterases, kinases, and phosphatases during unnatural sugar metabolism and provide guidance for ways to improve MOE. PMID:25957566

  17. Conclusions and recommendations from the symposium, Heart Healthy Omega-3s for Food: Stearidonic Acid (SDA) as a Sustainable Choice.

    PubMed

    Deckelbaum, Richard J; Calder, Philip C; Harris, William S; Akoh, Casimir C; Maki, Kevin C; Whelan, Jay; Banz, William J; Kennedy, Eileen

    2012-03-01

    Faculty who had presented at the symposium "Heart Healthy Omega-3s (n-3 fatty acids) for Food: Stearidonic Acid (SDA) as a Sustainable Choice" met and agreed upon conclusions and recommendations that could be made on the basis of evidence provided at the symposium. The participants also submitted manuscripts relating to their topics and these are presented in this supplement. These manuscripts were reviewed and also contributed to the conclusions and recommendations presented herein. The three major objectives of the symposium were to: 1) increase understanding of the current and emerging knowledge regarding the health benefits of (n-3) fatty acids (FA) including a focus on stearidonic acid (SDA) and EPA; 2) evaluate the importance of increasing (n-3) FA consumption in the US and the current challenge of doing so via mainstream foods; and 3) consider the health and food application benefits of SDA as a precursor to EPA and a plant-based sustainable source of highly unsaturated (n-3) FA for mainstream foods. Specific areas for future research were defined and included in the summary and conclusions herein. Overall evidence-based conclusions included: the current evidence provides a strong rationale for increasing (n-3) FA intakes in the US and other populations; current consumption of (n-3) FA in most populations is either insufficient or not efficient at providing adequate tissue levels of the long-chain (n-3) FA EPA and DHA; SDA in soybean oil appears to be a cost-effective and sustainable plant-based source that could contribute to reaching recommended levels of (n-3) FA intake, but more research and surveillance is needed; and adding SDA-enriched soybean oil to foods should be considered as a natural fortification approach to improving (n-3) FA status in the US and other populations. References for these conclusions and recommendations can be found in the articles included in the supplement.

  18. Sweet Conclusion

    ERIC Educational Resources Information Center

    Shirley, Britt M.; Wooldridge, Barbara Ross; Camp, Kerri M.

    2012-01-01

    Jen Harrington is the owner and pastry chef of Sweet Conclusion, a bakery in Tampa, Florida. Most of Harrington's business comes from baking wedding cakes, but she has been attempting to attract customers to her retail bakery, where she sells cupcakes, pies, ice cream, and coffee. Nearly four years she opened Sweet Conclusion, the retail part of…

  19. The metabolism of "surplus" amino acids.

    PubMed

    Bender, David A

    2012-08-01

    For an adult in N balance, apart from small amounts of amino acids required for the synthesis of neurotransmitters, hormones, etc, an amount of amino acids almost equal to that absorbed from the diet can be considered to be "surplus" in that it will be catabolized. The higher diet-induced thermogenesis from protein than from carbohydrate or fat has generally been assumed to be due to increased protein synthesis, which is ATP expensive. To this must be added the ATP cost of protein catabolism through the ubiquitin-proteasome pathway. Amino acid catabolism will add to thermogenesis. Deamination results in net ATP formation except when serine and threonine deaminases are used, but there is the energy cost of synthesizing glutamine in extra-hepatic tissues. The synthesis of urea has a net cost of only 1·5 × ATP when the ATP yield from fumarate metabolism is offset against the ATP cost of the urea cycle, but this offset is thermogenic. In fasting and on a low carbohydrate diet as much of the amino acid carbon as possible will be used for gluconeogenesis - an ATP-expensive, and hence thermogenic, process. Complete oxidation of most amino acid carbon skeletons also involves a number of thermogenic steps in which ATP (or GTP) or reduced coenzymes are utilized. There are no such thermogenic steps in the metabolism of pyruvate, acetyl CoA or acetoacetate, but for amino acids that are metabolized by way of the citric acid cycle intermediates there is thermogenesis ranging from 1 up to 7 × ATP equivalent per mol.

  20. Metabolic glycoengineering: sialic acid and beyond.

    PubMed

    Du, Jian; Meledeo, M Adam; Wang, Zhiyun; Khanna, Hargun S; Paruchuri, Venkata D P; Yarema, Kevin J

    2009-12-01

    This report provides a perspective on metabolic glycoengineering methodology developed over the past two decades that allows natural sialic acids to be replaced with chemical variants in living cells and animals. Examples are given demonstrating how this technology provides the glycoscientist with chemical tools that are beginning to reproduce Mother Nature's control over complex biological systems - such as the human brain - through subtle modifications in sialic acid chemistry. Several metabolic substrates (e.g., ManNAc, Neu5Ac, and CMP-Neu5Ac analogs) can be used to feed flux into the sialic acid biosynthetic pathway resulting in numerous - and sometime quite unexpected - biological repercussions upon nonnatural sialoside display in cellular glycans. Once on the cell surface, ketone-, azide-, thiol-, or alkyne-modified glycans can be transformed with numerous ligands via bioorthogonal chemoselective ligation reactions, greatly increasing the versatility and potential application of this technology. Recently, sialic acid glycoengineering methodology has been extended to other pathways with analog incorporation now possible in surface-displayed GalNAc and fucose residues as well as nucleocytoplasmic O-GlcNAc-modified proteins. Finally, recent efforts to increase the "druggability" of sugar analogs used in metabolic glycoengineering, which have resulted in unanticipated "scaffold-dependent" activities, are summarized.

  1. Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder

    PubMed Central

    Moe, Orson W.

    2014-01-01

    Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form. PMID:25045326

  2. Evaluation of endogenous acidic metabolic products associated with carbohydrate metabolism in tumor cells

    PubMed Central

    Mazzio, Elizabeth A.; Smith, Bruce

    2010-01-01

    Tumor cells have a high tolerance for acidic and hypoxic microenvironments, also producing abundant lactic acid through accelerated glycolysis in the presence or absence of O2. While the accumulation of lactate is thought to be a major contributor to the reduction of pH-circumscribing aggressive tumors, it is not known if other endogenous metabolic products contribute this acidity. Furthermore, anaerobic metabolism in cancer cells bears similarity to homo-fermentative lactic acid bacteria, however very little is known about an alternative pathway that may drive adenosine triphosphate (ATP) production independent of glycolysis. In this study, we quantify over 40 end-products (amines, acids, alcohols, aldehydes, or ketones) produced by malignant neuroblastoma under accelerated glycolysis (+glucose (GLU) supply 1–10 mM) ± mitochondrial toxin; 1-methyl-4-phenyl-pyridinium (MPP+) to abate aerobic respiration to delineate differences between anaerobic vs. aerobic cell required metabolic pathways. The data show that an acceleration of anaerobic glycolysis prompts an expected reduction in extracellular pH (pHex) from neutral to 6.7±0.006. Diverse metabolic acids associated with this drop in acidity were quantified by ionic exchange liquid chromatography (LC), showing concomitant rise in lactate (Ctrls 7.5±0.5 mM; +GLU 12.35±1.3 mM; +GLU + MPP 18.1±1.8 mM), acetate (Ctrl 0.84±0.13 mM: +GLU 1.3±0.15 mM; +GLU + MPP 2.7±0.4 mM), fumarate, and a-ketoglutarate (<10μM) while a range of other metabolic organic acids remained undetected. Amino acids quantified by o-phthalaldehyde precolumn derivatization/electrochemical detection–LC show accumulation of L-alanine (1.6±.052 mM), L-glutamate (285±9.7μM), L-asparagine (202±2.1μM), and L-aspartate (84.2±4.9μM) produced during routine metabolism, while other amino acids remain undetected. In contrast, the data show no evidence for accumulation of acetaldehyde, aldehydes, or ketones (Purpald/2

  3. Retinoic acid: its biosynthesis and metabolism.

    PubMed

    Napoli, J L

    1999-01-01

    This article presents a model that integrates the functions of retinoid-binding proteins with retinoid metabolism. One of these proteins, the widely expressed (throughout retinoid target tissues and in all vertebrates) and highly conserved cellular retinol-binding protein (CRBP), sequesters retinol in an internal binding pocket that segregates it from the intracellular milieu. The CRBP-retinol complex appears to be the quantitatively major form of retinol in vivo, and may protect the promiscuous substrate from nonenzymatic degradation and/or non-specific enzymes. For example, at least seven types of dehydrogenases catalyze retinal synthesis from unbound retinol in vitro (NAD+ vs. NADP+ dependent, cytosolic vs. microsomal, short-chain dehydrogenases/reductases vs. medium-chain alcohol dehydrogenases). But only a fraction of these (some of the short-chain de-hydrogenases/reductases) have the fascinating additional ability of catalyzing retinal synthesis from CRBP-bound retinol as well. Similarly, CRBP and/or other retinoid-binding proteins function in the synthesis of retinal esters, the reduction of retinal generated from intestinal beta-carotene metabolism, and retinoic acid metabolism. The discussion details the evidence supporting an integrated model of retinoid-binding protein/metabolism. Also addressed are retinoid-androgen interactions and evidence incompatible with ethanol causing fetal alcohol syndrome by competing directly with retinol dehydrogenation to impair retinoic acid biosynthesis.

  4. Ecophysiology of Crassulacean Acid Metabolism (CAM)

    PubMed Central

    LÜTTGE, ULRICH

    2004-01-01

    • Background and Scope Crassulacean Acid Metabolism (CAM) as an ecophysiological modification of photosynthetic carbon acquisition has been reviewed extensively before. Cell biology, enzymology and the flow of carbon along various pathways and through various cellular compartments have been well documented and discussed. The present attempt at reviewing CAM once again tries to use a different approach, considering a wide range of inputs, receivers and outputs. • Input Input is given by a network of environmental parameters. Six major ones, CO2, H2O, light, temperature, nutrients and salinity, are considered in detail, which allows discussion of the effects of these factors, and combinations thereof, at the individual plant level (‘physiological aut‐ecology’). • Receivers Receivers of the environmental cues are the plant types genotypes and phenotypes, the latter including morphotypes and physiotypes. CAM genotypes largely remain ‘black boxes’, and research endeavours of genomics, producing mutants and following molecular phylogeny, are just beginning. There is no special development of CAM morphotypes except for a strong tendency for leaf or stem succulence with large cells with big vacuoles and often, but not always, special water storage tissues. Various CAM physiotypes with differing degrees of CAM expression are well characterized. • Output Output is the shaping of habitats, ecosystems and communities by CAM. A number of systems are briefly surveyed, namely aquatic systems, deserts, salinas, savannas, restingas, various types of forests, inselbergs and paramós. • Conclusions While quantitative census data for CAM diversity and biomass are largely missing, intuition suggests that the larger CAM domains are those systems which are governed by a network of interacting stress factors requiring versatile responses and not systems where a single stress factor strongly prevails. CAM is noted to be a strategy for variable, flexible and plastic

  5. Articulation of three core metabolic processes in Arabidopsis: Fatty acid biosynthesis, leucine catabolism and starch metabolism

    PubMed Central

    Mentzen, Wieslawa I; Peng, Jianling; Ransom, Nick; Nikolau, Basil J; Wurtele, Eve Syrkin

    2008-01-01

    Background Elucidating metabolic network structures and functions in multicellular organisms is an emerging goal of functional genomics. We describe the co-expression network of three core metabolic processes in the genetic model plant Arabidopsis thaliana: fatty acid biosynthesis, starch metabolism and amino acid (leucine) catabolism. Results These co-expression networks form modules populated by genes coding for enzymes that represent the reactions generally considered to define each pathway. However, the modules also incorporate a wider set of genes that encode transporters, cofactor biosynthetic enzymes, precursor-producing enzymes, and regulatory molecules. We tested experimentally the hypothesis that one of the genes tightly co-expressed with starch metabolism module, a putative kinase AtPERK10, will have a role in this process. Indeed, knockout lines of AtPERK10 have an altered starch accumulation. In addition, the co-expression data define a novel hierarchical transcript-level structure associated with catabolism, in which genes performing smaller, more specific tasks appear to be recruited into higher-order modules with a broader catabolic function. Conclusion Each of these core metabolic pathways is structured as a module of co-expressed transcripts that co-accumulate over a wide range of environmental and genetic perturbations and developmental stages, and represent an expanded set of macromolecules associated with the common task of supporting the functionality of each metabolic pathway. As experimentally demonstrated, co-expression analysis can provide a rich approach towards understanding gene function. PMID:18616834

  6. Ferritin couples iron and fatty acid metabolism.

    PubMed

    Bu, Weiming; Liu, Renyu; Cheung-Lau, Jasmina C; Dmochowski, Ivan J; Loll, Patrick J; Eckenhoff, Roderic G

    2012-06-01

    A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 μM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 Å and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.

  7. Brain amino acid metabolism and ketosis.

    PubMed

    Yudkoff, M; Daikhin, Y; Nissim, I; Lazarow, A; Nissim, I

    2001-10-15

    The relationship between ketosis and brain amino acid metabolism was studied in mice that consumed a ketogenic diet (>90% of calories as lipid). After 3 days on the diet the blood concentration of 3-OH-butyrate was approximately 5 mmol/l (control = 0.06-0.1 mmol/l). In forebrain and cerebellum the concentration of 3-OH-butyrate was approximately 10-fold higher than control. Brain [citrate] and [lactate] were greater in the ketotic animals. The concentration of whole brain free coenzyme A was lower in ketotic mice. Brain [aspartate] was reduced in forebrain and cerebellum, but [glutamate] and [glutamine] were unchanged. When [(15)N]leucine was administered to follow N metabolism, this labeled amino acid accumulated to a greater extent in the blood and brain of ketotic mice. Total brain aspartate ((14)N + (15)N) was reduced in the ketotic group. The [(15)N]aspartate/[(15)N]glutamate ratio was lower in ketotic animals, consistent with a shift in the equilibrium of the aspartate aminotransferase reaction away from aspartate. Label in [(15)N]GABA and total [(15)N]GABA was increased in ketotic animals. When the ketotic animals were injected with glucose, there was a partial blunting of ketoacidemia within 40 min as well as an increase of brain [aspartate], which was similar to control. When [U-(13)C(6)]glucose was injected, the (13)C label appeared rapidly in brain lactate and in amino acids. Label in brain [U-(13)C(3)]lactate was greater in the ketotic group. The ratio of brain (13)C-amino acid/(13)C-lactate, which reflects the fraction of amino acid carbon that is derived from glucose, was much lower in ketosis, indicating that another carbon source, i.e., ketone bodies, were precursor to aspartate, glutamate, glutamine and GABA.

  8. Amino acids: metabolism, functions, and nutrition.

    PubMed

    Wu, Guoyao

    2009-05-01

    Recent years have witnessed the discovery that amino acids (AA) are not only cell signaling molecules but are also regulators of gene expression and the protein phosphorylation cascade. Additionally, AA are key precursors for syntheses of hormones and low-molecular weight nitrogenous substances with each having enormous biological importance. Physiological concentrations of AA and their metabolites (e.g., nitric oxide, polyamines, glutathione, taurine, thyroid hormones, and serotonin) are required for the functions. However, elevated levels of AA and their products (e.g., ammonia, homocysteine, and asymmetric dimethylarginine) are pathogenic factors for neurological disorders, oxidative stress, and cardiovascular disease. Thus, an optimal balance among AA in the diet and circulation is crucial for whole body homeostasis. There is growing recognition that besides their role as building blocks of proteins and polypeptides, some AA regulate key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. They are called functional AA, which include arginine, cysteine, glutamine, leucine, proline, and tryptophan. Dietary supplementation with one or a mixture of these AA may be beneficial for (1) ameliorating health problems at various stages of the life cycle (e.g., fetal growth restriction, neonatal morbidity and mortality, weaning-associated intestinal dysfunction and wasting syndrome, obesity, diabetes, cardiovascular disease, the metabolic syndrome, and infertility); (2) optimizing efficiency of metabolic transformations to enhance muscle growth, milk production, egg and meat quality and athletic performance, while preventing excess fat deposition and reducing adiposity. Thus, AA have important functions in both nutrition and health.

  9. Bile acid signaling in metabolic disease and drug therapy.

    PubMed

    Li, Tiangang; Chiang, John Y L

    2014-10-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.

  10. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    PubMed

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  11. Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.

    PubMed

    Rubio-Guerra, Alberto F; Morales-López, Herlinda; Garro-Almendaro, Ana K; Vargas-Ayala, German; Durán-Salgado, Montserrat B; Huerta-Ramírez, Saul; Lozano-Nuevo, Jose J

    2017-01-01

    Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia.

  12. Bile Acid Signaling in Metabolic Disease and Drug Therapy

    PubMed Central

    Li, Tiangang

    2014-01-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

  13. Metabolic engineering as a tool for enhanced lactic acid production.

    PubMed

    Upadhyaya, Bikram P; DeVeaux, Linda C; Christopher, Lew P

    2014-12-01

    Metabolic engineering is a powerful biotechnological tool that finds, among others, increased use in constructing microbial strains for higher lactic acid productivity, lower costs and reduced pollution. Engineering the metabolic pathways has concentrated on improving the lactic acid fermentation parameters, enhancing the acid tolerance of production organisms and their abilities to utilize a broad range of substrates, including fermentable biomass-derived sugars. Recent efforts have focused on metabolic engineering of lactic acid bacteria as they produce high yields and have a small genome size that facilitates their genetic manipulation. We summarize here the current trends in metabolic engineering techniques and strategies for manipulating lactic acid producing organisms developed to address and overcome major challenges in the lactic acid production process.

  14. Obesity diabetes and the role of bile acids in metabolism

    PubMed Central

    Owens, Daphne

    2016-01-01

    Abstract Bile acids have many activities over and above their primary function in aiding absorption of fat and fat soluble vitamins. Bile acids are synthesized from cholesterol, and thus are involved in cholesterol homeostasis. Bile acids stimulate glucagon-like peptide 1 (GLP1) production in the distal small bowel and colon, stimulating insulin secretion, and therefore, are involved in carbohydrate and fat metabolism. Bile acids through their insulin sensitising effect play a part in insulin resistance and type 2 diabetes. Bile acid metabolism is altered in obesity and diabetes. Both dietary restriction and weight loss due to bariatric surgery, alter the lipid carbohydrate and bile acid metabolism. Recent research suggests that the forkhead transcription factor FOXO is a central regulator of bile, lipid, and carbohydrate metabolism, but conflicting studies mean that our understanding of the complexity is not yet complete. PMID:28191525

  15. The function of oxalic acid in the human metabolism.

    PubMed

    Robertson, Daniel Stewart

    2011-09-01

    Biochemical reactions in cells which involve oxalic acid are described. It is shown that this compound is required for the formation of uracil and orotic acid. The former is a component of RNA which is common to all cells in the human metabolism. On the basis of the biochemical reactions described a possible treatment to relieve the effects of calcium oxalate renal calculi whose origin is related to the metabolic concentration of oxalic acid is proposed.

  16. Beyond intestinal soap--bile acids in metabolic control.

    PubMed

    Kuipers, Folkert; Bloks, Vincent W; Groen, Albert K

    2014-08-01

    Over the past decade, it has become apparent that bile acids are involved in a host of activities beyond their classic functions in bile formation and fat absorption. The identification of the farnesoid X receptor (FXR) as a nuclear receptor directly activated by bile acids and the discovery that bile acids are also ligands for the membrane-bound, G-protein coupled bile acid receptor 1 (also known as TGR5) have opened new avenues of research. Both FXR and TGR5 regulate various elements of glucose, lipid and energy metabolism. Consequently, a picture has emerged of bile acids acting as modulators of (postprandial) metabolism. Therefore, strategies that interfere with either bile acid metabolism or signalling cascades mediated by bile acids may represent novel therapeutic approaches for metabolic diseases. Synthetic modulators of FXR have been designed and tested, primarily in animal models. Furthermore, the use of bile acid sequestrants to reduce plasma cholesterol levels has unexpected benefits. For example, treatment of patients with type 2 diabetes mellitus (T2DM) with sequestrants causes substantial reductions in plasma levels of glucose and HbA1c. This Review aims to provide an overview of the molecular mechanisms by which bile acids modulate glucose and energy metabolism, particularly focusing on the glucose-lowering actions of bile acid sequestrants in insulin resistant states and T2DM.

  17. Amino Acid Flux from Metabolic Network Benefits Protein Translation: the Role of Resource Availability.

    PubMed

    Hu, Xiao-Pan; Yang, Yi; Ma, Bin-Guang

    2015-06-09

    Protein translation is a central step in gene expression and affected by many factors such as codon usage bias, mRNA folding energy and tRNA abundance. Despite intensive previous studies, how metabolic amino acid supply correlates with protein translation efficiency remains unknown. In this work, we estimated the amino acid flux from metabolic network for each protein in Escherichia coli and Saccharomyces cerevisiae by using Flux Balance Analysis. Integrated with the mRNA expression level, protein abundance and ribosome profiling data, we provided a detailed description of the role of amino acid supply in protein translation. Our results showed that amino acid supply positively correlates with translation efficiency and ribosome density. Moreover, with the rank-based regression model, we found that metabolic amino acid supply facilitates ribosome utilization. Based on the fact that the ribosome density change of well-amino-acid-supplied genes is smaller than poorly-amino-acid-supply genes under amino acid starvation, we reached the conclusion that amino acid supply may buffer ribosome density change against amino acid starvation and benefit maintaining a relatively stable translation environment. Our work provided new insights into the connection between metabolic amino acid supply and protein translation process by revealing a new regulation strategy that is dependent on resource availability.

  18. Metabolic strategies of beer spoilage lactic acid bacteria in beer.

    PubMed

    Geissler, Andreas J; Behr, Jürgen; von Kamp, Kristina; Vogel, Rudi F

    2016-01-04

    Beer contains only limited amounts of readily fermentable carbohydrates and amino acids. Beer spoilage lactic acid bacteria (LAB) have to come up with metabolic strategies in order to deal with selective nutrient content, high energy demand of hop tolerance mechanisms and a low pH. The metabolism of 26 LAB strains of 6 species and varying spoilage potentialwas investigated in order to define and compare their metabolic capabilities using multivariate statistics and outline possible metabolic strategies. Metabolic capabilities of beer spoilage LAB regarding carbohydrate and amino acids did not correlate with spoilage potential, but with fermentation type (heterofermentative/homofermentative) and species. A shift to mixed acid fermentation by homofermentative (hof) Pediococcus claussenii and Lactobacillus backii was observed as a specific feature of their growth in beer. For heterofermentative (hef) LAB a mostly versatile carbohydrate metabolism could be demonstrated, supplementing the known relevance of organic acids for their growth in beer. For hef LAB a distinct amino acid metabolism, resulting in biogenic amine production, was observed, presumably contributing to energy supply and pH homeostasis.

  19. EFFECTS OF HYDRAZINES ON THE METABOLISM OF CERTAIN AMINES AND AMINO ACIDS.

    DTIC Science & Technology

    AMINES, * AMINO ACIDS , *DIAMINE OXIDASE, TOXICITY, METABOLISM, METABOLISM, DIMETHYLHYDRAZINES, GLUTAMIC ACID, ENZYMES, PHARMACOLOGY, TRACER STUDIES, LABELED SUBSTANCES, RESPIRATION, GASTROINTESTINAL SYSTEM, RATS.

  20. Differential diagnosis of (inherited) amino acid metabolism or transport disorders.

    PubMed

    Blom, W; Huijmans, J G

    1992-02-01

    Disorders of amino acid metabolism or transport are most clearly expressed in urine. Nevertheless the interpretation of abnormalities in urinary amino acid excretion remains difficult. An increase or decrease of almost every amino acid in urine can be due to various etiology. To differentiate between primary and secondary aminoacido-pathies systematic laboratory investigation is necessary. Early diagnosis of disorders of amino acid metabolism or transport is very important, because most of them can be treated, leading to the prevention of (further) clinical abnormalities. In those disorders, which cannot be treated, early diagnosis in an index-patient may prevent the birth of other siblings by means of genetic counseling and prenatal diagnosis.Primary aminoacidopathies can be due to genetically determined transport disorders and enzyme deficiencies in amino acid metabolism or degradation. Secondary aminoacidopathies are the result of abnormal or deficient nutrition, intestinal dysfunction, organ pathology or other metabolic diseases like organic acidurias.A survey of amino acid metabolism and transport abnormalities will be given, illustrated with metabolic pathways and characteristic abnormal amino acid chromatograms.

  1. Amino acid composition and amino acid-metabolic network in supragingival plaque.

    PubMed

    Washio, Jumpei; Ogawa, Tamaki; Suzuki, Keisuke; Tsukiboshi, Yosuke; Watanabe, Motohiro; Takahashi, Nobuhiro

    2016-01-01

    Dental plaque metabolizes both carbohydrates and amino acids. The former can be degraded to acids mainly, while the latter can be degraded to various metabolites, including ammonia, acids and amines, and associated with acid-neutralization, oral malodor and tissue inflammation. However, amino acid metabolism in dental plaque is still unclear. This study aimed to elucidate what kinds of amino acids are available as metabolic substrates and how the amino acids are metabolized in supragingival plaque, by a metabolome analysis. Amino acids and the related metabolites in supragingival plaque were extracted and quantified comprehensively by CE-TOFMS. Plaque samples were also incubated with amino acids, and the amounts of ammonia and amino acid-related metabolites were measured. The concentration of glutamate was the highest in supragingival plaque, while the ammonia-production was the highest from glutamine. The obtained metabolome profile revealed that amino acids are degraded through various metabolic pathways, including deamination, decarboxylation and transamination and that these metabolic systems may link each other, as well as with carbohydrate metabolic pathways in dental plaque ecosystem. Moreover, glutamine and glutamate might be the main source of ammonia production, as well as arginine, and contribute to pH-homeostasis and counteraction to acid-induced demineralization in supragingival plaque.

  2. Metabolism of berry anthocyanins to phenolic acids in humans.

    PubMed

    Nurmi, Tarja; Mursu, Jaakko; Heinonen, Marina; Nurmi, Anna; Hiltunen, Raimo; Voutilainen, Sari

    2009-03-25

    We studied the metabolism of berry anthocyanins to phenolic acids in six human subjects by giving them bilberry-lingonberry puree with and without oat cereals. Puree + cereals contained 1435 micromol of anthocyanins and 339 micromol of phenolic acids. The urinary excretion of measured 18 phenolic acids increased 241 micromol during the 48 h follow-up after the puree + cereals supplementation. The excretion peak of dietary phenolic acids was observed at 4-6 h after the puree + cereals supplementation and 2 h earlier after the supplementation of the puree alone. Homovanillic and vanillic acids were the most abundant metabolites, and they were partly produced from anthocyanins. No gallic acid, a fragmentation product of delphinidin glycosides, was detected, and only a very low amount of malvidin glycosides was possibly metabolized to syringic acid. Although anthocyanins were partly fragmented to phenolic acids, still a large part of metabolites remained unknown.

  3. Citric acid cycle and role of its intermediates in metabolism.

    PubMed

    Akram, Muhammad

    2014-04-01

    The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It is the most important metabolic pathway for the energy supply to the body. TCA is the most important central pathway connecting almost all the individual metabolic pathways. In this review article, introduction, regulation and energetics of TCA cycle have been discussed. The present study was carried out to review literature on TCA cycle.

  4. Phosphatidic acid metabolism in rat liver cell nuclei.

    PubMed

    Gaveglio, Virginia L; Pasquaré, Susana J; Giusto, Norma M

    2013-04-02

    The aim of the present research was to analyze the pathways for phosphatidic acid metabolism in purified nuclei from liver. Lipid phosphate phosphatase, diacylglycerol lipase, monoacylglycerol lipase and PA-phospholipase type A activities were detected. The presence of lysophosphatidic acid significantly reduced DAG production while sphingosine 1-phoshate and ceramide 1-phosphate reduced MAG formation from PA. Using different enzymatic modulators (detergents and ions) an increase in the PA metabolism by phospholipase type A was observed. Our findings evidence an active PA metabolism in purified liver nuclei which generates important lipid second messengers, and which could thus be involved in nuclear processes such as gene transcription.

  5. Metabolic engineering strategies to bio-adipic acid production.

    PubMed

    Kruyer, Nicholas S; Peralta-Yahya, Pamela

    2017-03-30

    Adipic acid is the most industrially important dicarboxylic acid as it is a key monomer in the synthesis of nylon. Today, adipic acid is obtained via a chemical process that relies on petrochemical precursors and releases large quantities of greenhouse gases. In the last two years, significant progress has been made in engineering microbes for the production of adipic acid and its immediate precursors, muconic acid and glucaric acid. Not only have the microbial substrates expanded beyond glucose and glycerol to include lignin monomers and hemicellulose components, but the number of microbial chassis now goes further than Escherichia coli and Saccharomyces cerevisiae to include microbes proficient in aromatic degradation, cellulose secretion and degradation of multiple carbon sources. Here, we review the metabolic engineering and nascent protein engineering strategies undertaken in each of these chassis to convert different feedstocks to adipic, muconic and glucaric acid. We also highlight near term prospects and challenges for each of the metabolic routes discussed.

  6. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation.

    PubMed

    Kreft, Marko; Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2012-04-27

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation.

  7. Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

    PubMed Central

    Kreft, Marko; Bak, Lasse K; Waagepetersen, Helle S; Schousboe, Arne

    2012-01-01

    Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation. PMID:22435484

  8. Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome

    PubMed Central

    2012-01-01

    Background In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2) enzymes that regulate arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-6) acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases), DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases), brain-derived neurotrophic factor (BDNF), and synaptic integrity (drebrin and synaptophysin). Lipid concentrations were measured in brains subjected to high-energy microwave fixation. Results The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4) did not change. Conclusion These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome. PMID:23110484

  9. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    PubMed

    Lassandro, Carlotta; Banderali, Giuseppe; Radaelli, Giovanni; Borghi, Elisa; Moretti, Francesca; Verduci, Elvira

    2015-08-21

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  10. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    PubMed Central

    Lassandro, Carlotta; Banderali, Giuseppe; Radaelli, Giovanni; Borghi, Elisa; Moretti, Francesca; Verduci, Elvira

    2015-01-01

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome. PMID:26307979

  11. Regulation of hormone metabolism in Arabidopsis seeds: phytochrome regulation of abscisic acid metabolism and abscisic acid regulation of gibberellin metabolism.

    PubMed

    Seo, Mitsunori; Hanada, Atsushi; Kuwahara, Ayuko; Endo, Akira; Okamoto, Masanori; Yamauchi, Yukika; North, Helen; Marion-Poll, Annie; Sun, Tai-Ping; Koshiba, Tomokazu; Kamiya, Yuji; Yamaguchi, Shinjiro; Nambara, Eiji

    2006-11-01

    In a wide range of plant species, seed germination is regulated antagonistically by two plant hormones, abscisic acid (ABA) and gibberellin (GA). In the present study, we have revealed that ABA metabolism (both biosynthesis and inactivation) was phytochrome-regulated in an opposite fashion to GA metabolism during photoreversible seed germination in Arabidopsis. Endogenous ABA levels were decreased by irradiation with a red (R) light pulse in dark-imbibed seeds pre-treated with a far-red (FR) light pulse, and the reduction in ABA levels in response to R light was inhibited in a phytochrome B (PHYB)-deficient mutant. Expression of an ABA biosynthesis gene, AtNCED6, and the inactivation gene, CYP707A2, was regulated in a photoreversible manner, suggesting a key role for the genes in PHYB-mediated regulation of ABA metabolism. Abscisic acid-deficient mutants such as nced6-1, aba2-2 and aao3-4 exhibited an enhanced ability to germinate relative to wild type when imbibed in the dark after irradiation with an FR light pulse. In addition, the ability to synthesize GA was improved in the aba2-2 mutant compared with wild type during dark-imbibition after an FR light pulse. Activation of GA biosynthesis in the aba2-2 mutant was also observed during seed development. These data indicate that ABA is involved in the suppression of GA biosynthesis in both imbibed and developing seeds. Spatial expression patterns of the AtABA2 and AAO3 genes, responsible for last two steps of ABA biosynthesis, were distinct from that of the GA biosynthesis gene, AtGA3ox2, in both imbibed and developing seeds, suggesting that biosynthesis of ABA and GA in seeds occurs in different cell types.

  12. Decreased consumption of branched chain amino acids improves metabolic health

    PubMed Central

    Arriola Apelo, Sebastian I.; Neuman, Joshua C.; Kasza, Ildiko; Schmidt, Brian A.; Cava, Edda; Spelta, Francesco; Tosti, Valeria; Syed, Faizan A.; Baar, Emma L.; Veronese, Nicola; Cottrell, Sara E.; Fenske, Rachel J.; Bertozzi, Beatrice; Brar, Harpreet K.; Pietka, Terri; Bullock, Arnold D.; Figenshau, Robert S.; Andriole, Gerald L.; Merrins, Matthew J.; Alexander, Caroline M.; Kimple, Michelle E.; Lamming, Dudley W.

    2016-01-01

    Protein restricted, high carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Further, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderately protein restricted (PR) diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet, via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health, and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet. PMID:27346343

  13. Natural toxins that affect plant amino acid metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A diverse range of natural compounds interfere with the synthesis and other aspects of amino acid metabolism. Some are amino acid analogues, but most are not. This review covers a number of specific natural phytotoxic compounds by molecular target site. Inhibition of glutamine synthetase is of part...

  14. Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution.

    PubMed

    Liu, Jianguo; Wang, Qunhui; Zou, Hui; Liu, Yingying; Wang, Juan; Gan, Kemin; Xiang, Juan

    2013-11-01

    The (13) C isotope tracer method was used to investigate the glucose metabolic flux distribution and regulation in Lactobacillus amylophilus to improve lactic acid production using kitchen waste saccharified solution (KWSS). The results demonstrate that L. amylophilus is a homofermentative bacterium. In synthetic medium, 60.6% of the glucose entered the Embden-Meyerhof-Parnas (EMP) to produce lactic acid, whereas 36.4% of the glucose entered the pentose phosphate metabolic pathway (HMP). After solid-liquid separation of the KWSS, the addition of Fe(3+) during fermentation enhanced the NADPH production efficiency and increased the NADH content. The flux to the EMP was also effectively increased. Compared with the control (60.6% flux to EMP without Fe(3+) addition), the flux to the EMP with the addition of Fe(3+) (74.3%) increased by 23.8%. In the subsequent pyruvate metabolism, Fe(3+) also increased lactate dehydrogenase activity, and inhibited alcohol dehydrogenase, pyruvate dehydrogenase and pyruvate carboxylase, thereby increasing the lactic acid production to 9.03 g l(-1) , an increase of 8% compared with the control. All other organic acid by-products were lower than in the control. However, the addition of Zn(2+) showed an opposite effect, decreasing the lactic acid production. In conclusion it is feasible and effective means using GC-MS, isotope experiment and MATLAB software to integrate research the metabolic flux distribution of lactic acid bacteria, and the results provide the theoretical foundation for similar metabolic flux distribution.

  15. Metabolism of amino acids, dipeptides and tetrapeptides by Lactobacillus sakei.

    PubMed

    Sinz, Quirin; Schwab, Wilfried

    2012-04-01

    The microbial degradation of proteins, peptides and amino acids generates volatiles involved in the typical flavor of dry fermented sausage. The ability of three Lactobacillus sakei strains to form aroma compounds was investigated. Whole resting cells were fermented in phosphate buffer with equimolar amounts of substrates consisting of dipeptides, tetrapeptides and free amino acids, respectively. Dipeptides disappeared quickly from the solutions whereas tetrapeptides were only partially degraded. In both approaches the concentration of free amino acids increased in the reaction mixture but did not reach the equimolar amount of the initial substrates. When free amino acids were fed to the bacteria their levels decreased only slightly. Although peptides were more rapidly degraded and/or transported into the cells, free amino acids produced higher amounts of volatiles. It is suggested, that after transport into the cell peptides are only partially hydrolyzed to their amino acids, while the rest is metabolized via alternative metabolic pathways. The three L. sakei strains differed to some extend in their ability to metabolize the substrates to volatile compounds. In a few cases this was due to the position of the amino acids within the peptides. Compared to other starter cultures used for the production of dry fermented sausages, the metabolic impact of the L. sakei strains on the formation of volatiles was very low.

  16. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    PubMed Central

    2010-01-01

    Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary

  17. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    PubMed

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.

  18. IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

    PubMed Central

    Grassian, Alexandra R.; Parker, Seth J.; Davidson, Shawn M.; Divakarun, Ajit S.; Green, Courtney R.; Zhang, Xiamei; Slocum, Kelly L.; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D.; Straub, Christopher; Growney, Joseph D.; Vander Heiden, Matthew G.; Murphy, Anne N.; Pagliarini, Raymond; Metallo, Christian M.

    2016-01-01

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. PMID:24755473

  19. Can valproic acid be an inducer of clozapine metabolism?

    PubMed Central

    Diaz, Francisco J.; Eap, Chin B.; Ansermot, Nicolas; Crettol, Severine; Spina, Edoardo; de Leon, Jose

    2014-01-01

    Introduction Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that 1) VPA is a net inducer of clozapine metabolism, and 2) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. Methods After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. Results VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14% to 39%) after controlling for confounding variables including smoking (35% lower, 28% to 56%). Discussion Prospective studies are needed to definitively establish that VPA may 1) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and 2) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism. PMID:24764199

  20. Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism.

    PubMed

    Kim, Yoo; Kim, Jonggun; Whang, Kwang-Youn; Park, Yeonhwa

    2016-02-01

    Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.

  1. Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity

    PubMed Central

    Van heusden, J; Van Ginckel, R; Bruwiere, H; Moelans, P; Janssen, B; Floren, W; van der Leede, B J; van Dun, J; Sanz, G; Venet, M; Dillen, L; Van Hove, C; Willemsens, G; Janicot, M; Wouters, W

    2002-01-01

    All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg−1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action. British Journal of Cancer (2002) 86, 605–611. DOI: 10.1038/sj/bjc/6600056 www.bjcancer.com © 2002 Cancer Research UK PMID:11870544

  2. Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity.

    PubMed

    Van Heusden, J; Van Ginckel, R; Bruwiere, H; Moelans, P; Janssen, B; Floren, W; van der Leede, B J; van Dun, J; Sanz, G; Venet, M; Dillen, L; Van Hove, C; Willemsens, G; Janicot, M; Wouters, W

    2002-02-12

    All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC(50)-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg(-1). In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action.

  3. Metabolism of hydroxycinnamic acids and their tartaric acid esters by Brettanomyces and Pediococcus in red wines.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Caffeic, p-coumaric, and ferulic acids and their corresponding tartaric acid esters (caftaric, coutaric, and fertaric, respectively) are found in wines in varying concentrations. While Brettanomyces and Pediococcus can utilize the free acids, it is not known whether they can metabolize the correspon...

  4. Bile acid metabolism and signaling in cholestasis, inflammation and cancer

    PubMed Central

    Apte, Udayan

    2015-01-01

    Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid soluble vitamins. Bile acid synthesis, transport and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration and carcinogenesis. PMID:26233910

  5. Bile Acid Metabolism and Signaling in Cholestasis, Inflammation, and Cancer.

    PubMed

    Li, Tiangang; Apte, Udayan

    2015-01-01

    Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles in bile acid synthesis. Bile acids are physiological detergent molecules, so are highly cytotoxic. They undergo enterohepatic circulation and play important roles in generating bile flow and facilitating biliary secretion of endogenous metabolites and xenobiotics and intestinal absorption of dietary fats and lipid-soluble vitamins. Bile acid synthesis, transport, and pool size are therefore tightly regulated under physiological conditions. In cholestasis, impaired bile flow leads to accumulation of bile acids in the liver, causing hepatocyte and biliary injury and inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis, and eventually liver failure. Chronic cholestasis also increases the risk of developing hepatocellular or cholangiocellular carcinomas. Extensive research in the last two decades has shown that bile acids act as signaling molecules that regulate various cellular processes. The bile acid-activated nuclear receptors are ligand-activated transcriptional factors that play critical roles in the regulation of bile acid, drug, and xenobiotic metabolism. In cholestasis, these bile acid-activated receptors regulate a network of genes involved in bile acid synthesis, conjugation, transport, and metabolism to alleviate bile acid-induced inflammation and injury. Additionally, bile acids are known to regulate cell growth and proliferation, and altered bile acid levels in diseased conditions have been implicated in liver injury/regeneration and tumorigenesis. We will cover the mechanisms that regulate bile acid homeostasis and detoxification during cholestasis, and the roles of bile acids in the initiation and regulation of hepatic inflammation, regeneration, and carcinogenesis.

  6. Higher plant metabolism and energetics in hypogravity: Amino acid metabolism in higher plants

    NASA Technical Reports Server (NTRS)

    Mazelis, M.

    1976-01-01

    Laboratory's investigation into the amino acid metabolism of dwarf marigolds exposed to an environment of simulated hypogravity is summarized. Using both in vivo, and/or in vitro studies, the following effects of hypogravitational stress have been shown: (1) increased proline incorporation into cell wall protein, (2) inhibition of amino acid decarboxylation, (3) decrease in glutamic acid decarboxylase activity; and (4) decrease in the relative amount of a number of soluble amino acids present in deproteinized extracts of marigold leaves. It is concluded from these data there are several rapid, major alterations in amino acid metabolism associated with hypogravitational stress in marigolds. The mechanism(s) and generality of these effects with regard to other species is still unknown.

  7. Fatty acid metabolism in lambs fed citrus pulp.

    PubMed

    Lanza, M; Scerra, M; Bognanno, M; Buccioni, A; Cilione, C; Biondi, L; Priolo, A; Luciano, G

    2015-06-01

    (P = 0.09) with increasing level of citrus pulp in the diets. Furthermore, the SA/(SA + VA) ratio tended to be lower (P = 0.10) in the ruminal fluid from lambs fed the CIT35 diet compared with that of the CON group. In conclusion, our results support the hypothesis that replacing barley with citrus pulp in the diet of growing lambs improves intramuscular fatty acid composition and underline the need for specific studies to clarify the mechanisms by which feeding citrus pulp affects the fatty acid metabolism in ruminants.

  8. Amino acid metabolism in tumour-bearing mice.

    PubMed Central

    Rivera, S; Azcón-Bieto, J; López-Soriano, F J; Miralpeix, M; Argilés, J M

    1988-01-01

    Mice bearing the Lewis lung carcinoma showed a high tumour glutaminase activity and significantly higher concentrations of most amino acids than in both the liver and the skeletal muscle of the host. Tumour tissue slices showed a marked preference for glutamine, especially for oxidation of its skeleton to CO2. It is proposed that the metabolism of this particular carcinoma is focused on amino acid degradation, glutamine being its preferred substrate. PMID:3342022

  9. Ganoderic Acid A Metabolites and Their Metabolic Kinetics.

    PubMed

    Cao, Fang-Rui; Feng, Li; Ye, Lin-Hu; Wang, Li-Sha; Xiao, Bing-Xin; Tao, Xue; Chang, Qi

    2017-01-01

    Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and urine after intravenous administration to rats (20 mg/kg), and in vitro by incubating with rat liver microsomes (RLMs) and human liver microsomes (HLMs); (2) to investigate the metabolic kinetics of main GAA metabolites. Using HPLC-DAD-MS/MS techniques, a total of 37 metabolites were tentatively characterized from in vivo samples based on their fragmentation behaviors. The metabolites detected in in vitro samples were similar to those found in vivo. GAA underwent extensive phase I and II metabolism. The main metabolic soft spots of GAA were 3, 7, 11, 15, 23-carbonyl groups (or hydroxyl groups) and 12, 20, 28 (29)-carbon atoms. Ganoderic acid C2 (GAC2) and 7β,15-dihydroxy-3,11,23-trioxo-lanost-26-oic acid were two main reduction metabolites of GAA, and their kinetics followed classical hyperbolic kinetics. The specific isoenzyme responsible for the biotransformation of the two metabolites in RLMs and HLMs was CYP3A. This is the first report on the comprehensive metabolism of GAA, as well as the metabolic kinetics of its main metabolites.

  10. Dynamic modeling of lactic acid fermentation metabolism with Lactococcus lactis.

    PubMed

    Oh, Euhlim; Lu, Mingshou; Park, Changhun; Park, Changhun; Oh, Han Bin; Lee, Sang Yup; Lee, Jinwon

    2011-02-01

    A dynamic model of lactic acid fermentation using Lactococcus lactis was constructed, and a metabolic flux analysis (MFA) and metabolic control analysis (MCA) were performed to reveal an intensive metabolic understanding of lactic acid bacteria (LAB). The parameter estimation was conducted with COPASI software to construct a more accurate metabolic model. The experimental data used in the parameter estimation were obtained from an LC-MS/ MS analysis and time-course simulation study. The MFA results were a reasonable explanation of the experimental data. Through the parameter estimation, the metabolic system of lactic acid bacteria can be thoroughly understood through comparisons with the original parameters. The coefficients derived from the MCA indicated that the reaction rate of L-lactate dehydrogenase was activated by fructose 1,6-bisphosphate and pyruvate, and pyruvate appeared to be a stronger activator of L-lactate dehydrogenase than fructose 1,6-bisphosphate. Additionally, pyruvate acted as an inhibitor to pyruvate kinase and the phosphotransferase system. Glucose 6-phosphate and phosphoenolpyruvate showed activation effects on pyruvate kinase. Hexose transporter was the strongest effector on the flux through L-lactate dehydrogenase. The concentration control coefficient (CCC) showed similar results to the flux control coefficient (FCC).

  11. Ganoderic Acid A Metabolites and Their Metabolic Kinetics

    PubMed Central

    Cao, Fang-Rui; Feng, Li; Ye, Lin-Hu; Wang, Li-Sha; Xiao, Bing-Xin; Tao, Xue; Chang, Qi

    2017-01-01

    Ganoderic acid A (GAA), a representative active triterpenoid from Ganoderma lucidum, has been reported to exhibit antinociceptive, antioxidative, cytotoxic, hepatoprotective and anticancer activities. The present study aims (1) to identify GAA metabolites, in vivo by analyzing the bile, plasma and urine after intravenous administration to rats (20 mg/kg), and in vitro by incubating with rat liver microsomes (RLMs) and human liver microsomes (HLMs); (2) to investigate the metabolic kinetics of main GAA metabolites. Using HPLC-DAD-MS/MS techniques, a total of 37 metabolites were tentatively characterized from in vivo samples based on their fragmentation behaviors. The metabolites detected in in vitro samples were similar to those found in vivo. GAA underwent extensive phase I and II metabolism. The main metabolic soft spots of GAA were 3, 7, 11, 15, 23-carbonyl groups (or hydroxyl groups) and 12, 20, 28 (29)-carbon atoms. Ganoderic acid C2 (GAC2) and 7β,15-dihydroxy-3,11,23-trioxo-lanost-26-oic acid were two main reduction metabolites of GAA, and their kinetics followed classical hyperbolic kinetics. The specific isoenzyme responsible for the biotransformation of the two metabolites in RLMs and HLMs was CYP3A. This is the first report on the comprehensive metabolism of GAA, as well as the metabolic kinetics of its main metabolites. PMID:28326038

  12. Sialic acid metabolism and sialyltransferases: natural functions and applications

    PubMed Central

    Li, Yanhong

    2012-01-01

    Sialic acids are a family of negatively charged monosaccharides which are commonly presented as the terminal residues in glycans of the glycoconjugates on eukaryotic cell surface or as components of capsular polysaccharides or lipooligosaccharides of some pathogenic bacteria. Due to their important biological and pathological functions, the biosynthesis, activation, transfer, breaking down, and recycle of sialic acids are attracting increasing attention. The understanding of the sialic acid metabolism in eukaryotes and bacteria leads to the development of metabolic engineering approaches for elucidating the important functions of sialic acid in mammalian systems and for large-scale production of sialosides using engineered bacterial cells. As the key enzymes in biosynthesis of sialylated structures, sialyltransferases have been continuously identified from various sources and characterized. Protein crystal structures of seven sialyltransferases have been reported. Wild-type sialyltransferases and their mutants have been applied with or without other sialoside biosynthetic enzymes for producing complex sialic acid-containing oligosaccharides and glycoconjugates. This mini-review focuses on current understanding and applications of sialic acid metabolism and sialyltransferases. PMID:22526796

  13. Amino acid metabolism and protein synthesis in malarial parasites*

    PubMed Central

    Sherman, I. W.

    1977-01-01

    Malaria-infected red cells and free parasites have limited capabilities for the biosynthesis of amino acids. Therefore, the principal amino acid sources for parasite protein synthesis are the plasma free amino acids and host cell haemoglobin. Infected cells and plasmodia incorporate exogenously supplied amino acids into protein. However, the hypothesis that amino acid utilization (from an external source) is related to availability of that amino acid in haemoglobin is without universal support: it is true for isoleucine and for Plasmodium knowlesi and P. falciparum, but not for methionine, cysteine, and other amino acids, and it does not apply to P. lophurae. More by default than by direct evidence, haemoglobin is believed to be the main amino acid reservoir available to the intraerythrocytic plasmodium. Haemoglobin, ingested via the cytostome, is held in food vacuoles where auto-oxidation takes place. As a consequence, haem is released and accumulates in the vacuole as particulate haemozoin (= malaria pigment). Current evidence favours the view that haemozoin is mainly haematin. Acid and alkaline proteases (identified in crude extracts from mammalian and avian malarias) are presumably secreted directly into the food vacuole. They then digest the denatured globin and the resulting amino acids are incorporated into parasite protein. Cell-free protein synthesizing systems have been developed using P. knowlesi and P. lophurae ribosomes. In the main these systems are typically eukaryotic. Studies of amino acid metabolism are exceedingly limited. Arginine, lysine, methionine, and proline are incorporated into protein, whereas glutamic acid is metabolized via an NADP-specific glutamic dehydrogenase. Glutamate oxidation generates NADPH and auxiliary energy (in the form of α-ketoglutarate). The role of red cell glutathione in the economy of the parasite remains obscure. Important goals for future research should be: quantitative assessment of the relative importance of

  14. Carnitine is associated with fatty acid metabolism in plants.

    PubMed

    Bourdin, Benoîte; Adenier, Hervé; Perrin, Yolande

    2007-12-01

    The finding of acylcarnitines alongside free carnitine in Arabidopsis thaliana and other plant species, using tandem mass spectrometry coupled to liquid chromatography shows a link between carnitine and plant fatty acid metabolism. Moreover the occurrence of both medium- and long-chain acylcarnitines suggests that carnitine is connected to diverse fatty acid metabolic pathways in plant tissues. The carnitine and acylcarnitine contents in plant tissues are respectively a hundred and a thousand times lower than in animal tissues, and acylcarnitines represent less than 2% of the total carnitine pool whereas this percentage reaches 30% in animal tissues. These results suggest that carnitine plays a lesser role in lipid metabolism in plants than it does in animals.

  15. Analysis of the aspartic acid metabolic pathway using mutant genes.

    PubMed

    Azevedo, R A

    2002-01-01

    Amino acid metabolism is a fundamental process for plant growth and development. Although a considerable amount of information is available, little is known about the genetic control of enzymatic steps or regulation of several pathways. Much of the information about biochemical pathways has arisen from the use of mutants lacking key enzymes. Although mutants were largely used already in the 60's, by bacterial and fungal geneticists, it took plant research a long time to catch up. The advance in this area was rapid in the 80's, which was followed in the 90's by the development of techniques of plant transformation. In this review we present an overview of the aspartic acid metabolic pathway, the key regulatory enzymes and the mutants and transgenic plants produced for lysine and threonine metabolism. We also discuss and propose a new study of high-lysine mutants.

  16. Nicotinamide metabolism in ferns: formation of nicotinic acid glucoside.

    PubMed

    Ashihara, Hiroshi; Yin, Yuling; Watanabe, Shin

    2011-03-01

    The metabolic fate of [carbonyl-(14)C]nicotinamide was investigated in 9 fern species, Psilotum nudum, Angiopteris evecta, Lygodium japonicum, Acrostichum aureum, Asplenium antiquum, Diplazium subsinuatum, Thelypteris acuminate, Blechnum orientale and Crytomium fortune. All fern species produce a large quantity of nicotinic acid glucoside from [(14)C]nicotinamide, but trigonelline formation is very low. Increases in the release of (14)CO(2) with incubation time was accompanied by decreases in [carboxyl-(14)C]nicotinic acid glucoside. There was slight stimulation of nicotinic acid glucoside formation by 250 mM NaCl in mature leaves of the mangrove fern, Acrostichum aureum, but it is unlikely that this compound acts as a compatible solute. Nicotinamide and nicotinic acid salvage for pyridine nucleotide synthesis was detected in all fern species, although this activity was always less than nicotinic acid glucoside synthesis. Predominant formation of nicotinic acid glucoside is characteristic of nicotinic acid metabolism in ferns. This reaction appears to act as a detoxication mechanism, removing excess nicotinic acid.

  17. Arachidonic acid metabolism in cultured mouse keratinocytes

    SciTech Connect

    Kondoh, H.; Sato, Y.; Kanoh, H.

    1985-07-01

    The authors attempted to characterize the general features of arachidonate metabolism in cultured mouse keratinocytes. The cells labeled with (/sup 3/H)arachidonate were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), ionophore A23187, and fetal bovine serum (FBS). Common to the three substances, phosphatidylinositol, phosphatidylethanolamine, and phosphatidylcholine almost equally served as sources of arachidonate liberated by the action of phospholipase A2. The stimulation of phospholipase A2 action was observed in the order of A23187 greater than FBS greater than TPA. When stimulated by TPA or A23187, the radioactivity released into the extracellular medium was mostly found in prostaglandin (PG) E2. Formation of other PGs and hydroxyeicosatetraenoate (HETE) was extremely limited. In the case of stimulation by FBS, however, the released radioactivity was mainly associated with non-converted arachidonate. FBS also inhibited the TPA- and A23187-induced conversion of arachidonate to PGE2. Phospholipid degradation induced by the three stimulators was similarly dependent on extracellular Ca/sup 2 +/. The stimulation by FBS and A23187 was suppressed by calmodulin antagonists, though the effect of A23187 was much more sensitive to the antagonists when compared to that of FBS. The authors observed more than additive effects of the three stimulators when tested together.

  18. Fatty acid metabolism in pulmonary arterial hypertension: role in right ventricular dysfunction and hypertrophy

    PubMed Central

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a complex, multifactorial disease in which an increase in pulmonary vascular resistance leads to increased afterload on the right ventricle (RV), causing right heart failure and death. Our understanding of the pathophysiology of RV dysfunction in PAH is limited but is constantly improving. Increasing evidence suggests that in PAH RV dysfunction is associated with various components of metabolic syndrome, such as insulin resistance, hyperglycemia, and dyslipidemia. The relationship between RV dysfunction and fatty acid/glucose metabolites is multifaceted, and in PAH it is characterized by a shift in utilization of energy sources toward increased glucose utilization and reduced fatty acid consumption. RV dysfunction may be caused by maladaptive fatty acid metabolism resulting from an increase in fatty acid uptake by fatty acid transporter molecule CD36 and an imbalance between glucose and fatty acid oxidation in mitochondria. This leads to lipid accumulation in the form of triglycerides, diacylglycerol, and ceramides in the cytoplasm, hallmarks of lipotoxicity. Current interventions in animal models focus on improving RV dysfunction through altering fatty acid oxidation rates and limiting lipid accumulation, but more specific and effective therapies may be available in the coming years based on current research. In conclusion, a deeper understanding of the complex mechanisms of the metabolic remodeling of the RV will aid in the development of targeted treatments for RV failure in PAH. PMID:26064451

  19. Regulation of amino acid metabolic enzymes and transporters in plants.

    PubMed

    Pratelli, Réjane; Pilot, Guillaume

    2014-10-01

    Amino acids play several critical roles in plants, from providing the building blocks of proteins to being essential metabolites interacting with many branches of metabolism. They are also important molecules that shuttle organic nitrogen through the plant. Because of this central role in nitrogen metabolism, amino acid biosynthesis, degradation, and transport are tightly regulated to meet demand in response to nitrogen and carbon availability. While much is known about the feedback regulation of the branched biosynthesis pathways by the amino acids themselves, the regulation mechanisms at the transcriptional, post-transcriptional, and protein levels remain to be identified. This review focuses mainly on the current state of our understanding of the regulation of the enzymes and transporters at the transcript level. Current results describing the effect of transcription factors and protein modifications lead to a fragmental picture that hints at multiple, complex levels of regulation that control and coordinate transport and enzyme activities. It also appears that amino acid metabolism, amino acid transport, and stress signal integration can influence each other in a so-far unpredictable fashion.

  20. Relation between uric acid and metabolic syndrome in subjects with cardiometabolic risk

    PubMed Central

    da Silva, Hellen Abreu; Carraro, Júlia Cristina Cardoso; Bressan, Josefina; Hermsdorff, Helen Hermana Miranda

    2015-01-01

    Objective To identify possible relations between serum uric acid levels and metabolic syndrome and its components in a population with cardiometabolic risk. Methods This cross-sectional study included 80 subjects (46 women), with mean age of 48±16 years, seen at the Cardiovascular Health Program. Results The prevalence of hyperuricemia and metabolic syndrome was 6.3% and 47.1%, respectively. Uric acid level was significantly higher in individuals with metabolic syndrome (5.1±1.6mg/dL), as compared to those with no syndrome or with pre-syndrome (3.9±1.2 and 4.1±1.3mg/dL, respectively; p<0.05). The uric acid levels were significantly higher in men presenting abdominal obesity, and among women with abdominal obesity, lower HDL-c levels and higher blood pressure (p<0.05). Conclusion Uric acid concentrations were positively related to the occurrence of metabolic syndrome and its components, and there were differences between genders. Our results indicate serum uric acid as a potential biomarker for patients with cardiometabolic risk. PMID:26018145

  1. Metabolism of Sialic Acid by Bifidobacterium breve UCC2003

    PubMed Central

    Egan, Muireann; O'Connell Motherway, Mary; Ventura, Marco

    2014-01-01

    Bifidobacteria constitute a specific group of commensal bacteria that inhabit the gastrointestinal tracts of humans and other mammals. Bifidobacterium breve UCC2003 has previously been shown to utilize several plant-derived carbohydrates that include cellodextrins, starch, and galactan. In the present study, we investigated the ability of this strain to utilize the mucin- and human milk oligosaccharide (HMO)-derived carbohydrate sialic acid. Using a combination of transcriptomic and functional genomic approaches, we identified a gene cluster dedicated to the uptake and metabolism of sialic acid. Furthermore, we demonstrate that B. breve UCC2003 can cross feed on sialic acid derived from the metabolism of 3′-sialyllactose, an abundant HMO, by another infant gut bifidobacterial strain, Bifidobacterium bifidum PRL2010. PMID:24814790

  2. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    SciTech Connect

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-09-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.

  3. Metabolic evolution of Escherichia coli strains that produce organic acids

    DOEpatents

    Grabar, Tammy; Gong, Wei; Yocum, R Rogers

    2014-10-28

    This invention relates to the metabolic evolution of a microbial organism previously optimized for producing an organic acid in commercially significant quantities under fermentative conditions using a hexose sugar as sole source of carbon in a minimal mineral medium. As a result of this metabolic evolution, the microbial organism acquires the ability to use pentose sugars derived from cellulosic materials for its growth while retaining the original growth kinetics, the rate of organic acid production and the ability to use hexose sugars as a source of carbon. This invention also discloses the genetic change in the microorganism that confers the ability to use both the hexose and pentose sugars simultaneously in the production of commercially significant quantities of organic acids.

  4. Nickel deficiency disrupts metabolism of ureides, amino acids, and organic acids of young pecan foliage.

    PubMed

    Bai, Cheng; Reilly, Charles C; Wood, Bruce W

    2006-02-01

    The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan.

  5. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

  6. Arachidonic acid metabolism in human prostate cancer

    PubMed Central

    YANG, PEIYING; CARTWRIGHT, CARRIE A.; LI, JIN; WEN, SIJIN; PROKHOROVA, INA N.; SHUREIQI, IMAD; TRONCOSO, PATRICIA; NAVONE, NORA M.; NEWMAN, ROBERT A.; KIM, JERI

    2012-01-01

    The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. PMID:22895552

  7. Citric acid metabolism in hetero- and homofermentative lactic acid bacteria.

    PubMed Central

    Drinan, D F; Robin, S; Cogan, T M

    1976-01-01

    The effect of citrate on production of diacetyl and acetoin by four strains each of heterofermentative and homofermentative lactic acid bacteria capable of utilizing citrate was studied. Acetoin was quantitatively the more important compound. The heterofermentative bacteria produced no acetoin or diacetyl in the absence of citrate, and two strains produced traces of acetoin in its presence. Citrate stimulated the growth rate of the heterofermentative lactobacilli. Acidification of all heterofermentative cultures with citric acid resulted in acetoin production. Destruction of accumulated acetoin appeared to coincide with the disappearance of citrate. All homofermentative bacteria produced more acetoin and diacetyl in the presence of citrate than in its absence. Citrate utilization was begun immediately by the streptococci but was delayed until at least the middle of the exponential phase in the case of the lactobacilli. PMID:5054

  8. The Contributing Role of Bile Acids to Metabolic Improvements After Obesity and Metabolic Surgery.

    PubMed

    Fouladi, Farnaz; Mitchell, James E; Wonderlich, Joseph A; Steffen, Kristine J

    2016-10-01

    Obesity and metabolic surgery (OMS) leads to several metabolic improvements, which often occur prior to substantial weight loss. Therefore, other factors in addition to weight loss contribute to the metabolic benefits. This literature review offers an overview of studies investigating bile acids (BAs) and their metabolic effects after OMS. Rearrangement of enterohepatic circulation, changes in BA synthesis, BA conjugation, intestinal reabsorption, and alterations in the gut microbiota are potential mechanisms for altered BA profiles after surgery. Increased BA levels are associated with improved glucose homeostasis and lipid profiles, which are mediated by two major receptors: the Transmembrane G-protein Coupled Receptor and the Farnesoid X Receptor. Therefore, pharmacological manipulation of BAs and their receptors may be viable targets for less invasive obesity treatment.

  9. Glutaric acid moderately compromises energy metabolism in rat brain.

    PubMed

    da C Ferreira, Gustavo; Viegas, Carolina M; Schuck, Patrícia F; Latini, Alexandra; Dutra-Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Vargas, Carmen R; Wajner, Moacir

    2005-12-01

    Glutaric acidemia type I is an inherited metabolic disorder biochemically characterized by tissue accumulation of predominantly glutaric acid (GA). Affected patients present frontotemporal hypotrophy, as well as caudate and putamen injury following acute encephalopathic crises. Considering that the underlying mechanisms of basal ganglia damage in this disorder are poorly known, in the present study we tested the effects of glutaric acid (0.2-5mM) on critical enzyme activities of energy metabolism, namely the respiratory chain complexes I-IV, succinate dehydrogenase and creatine kinase in midbrain of developing rats. Glutaric acid significantly inhibited creatine kinase activity (up to 26%) even at the lowest dose used in the assays (0.2mM). We also observed that CK inhibition was prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of GA was possibly mediated by oxidation of essential thiol groups of the enzyme. In addition, the activities of the respiratory chain complex I-III and of succinate dehydrogenase were also significantly inhibited by 20 and 30%, respectively, at the highest glutaric acid concentration tested (5mM). In contrast, complexes II-III and IV activities of the electron transport chain were not affected by the acid. The effect of glutaric acid on the rate of oxygen consumption in intact mitochondria from the rat cerebrum was also investigated. Glutaric acid (1mM) significantly lowered the respiratory control ratio (state III/state IV) up to 40% in the presence of the respiratory substrates glutamate/malate or succinate. Moreover, state IV respiration linked to NAD and FAD substrates was significantly increased in GA-treated mitochondria while state III was significantly diminished. The results indicate that the major metabolite accumulating in glutaric acidemia type I moderately compromises brain energy metabolism in vitro.

  10. Acid-base metabolism: implications for kidney stones formation.

    PubMed

    Hess, Bernhard

    2006-04-01

    The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ <--> NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization.

  11. Oxalic acid alleviates chilling injury in peach fruit by regulating energy metabolism and fatty acid contents.

    PubMed

    Jin, Peng; Zhu, Hong; Wang, Lei; Shan, Timin; Zheng, Yonghua

    2014-10-15

    The effects of postharvest oxalic acid (OA) treatment on chilling injury, energy metabolism and membrane fatty acid content in 'Baifeng' peach fruit stored at 0°C were investigated. Internal browning was significantly reduced by OA treatment in peaches. OA treatment markedly inhibited the increase of ion leakage and the accumulation of malondialdehyde. Meanwhile, OA significantly increased the contents of adenosine triphosphate and energy charge in peach fruit. Enzyme activities of energy metabolism including H(+)-adenosine triphosphatase, Ca(2+)-adenosine triphosphatase, succinic dehydrogenase and cytochrome C oxidase were markedly enhanced by OA treatment. The ratio of unsaturated/saturated fatty acid in OA-treated fruit was significantly higher than that in control fruit. These results suggest that the alleviation in chilling injury by OA may be due to enhanced enzyme activities related to energy metabolism and higher levels of energy status and unsaturated/saturated fatty acid ratio.

  12. Serum fatty acid binding protein 4, free fatty acids and metabolic risk markers

    PubMed Central

    Karakas, Sidika E.; Almario, Rogelio U.; Kim, Kyoungmi

    2009-01-01

    Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFA) in the adipocytes during lipolysis. Serum FFA relates to Metabolic Syndrome (METS) and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test (OGTT). Insulin resistance was determined using frequently sampled intravenous GTT (FS-IVGTT). Serum lipids and inflammation markers were measured at fasting. During OGTT, serum FABP4 decreased by 40%, reaching its nadir at 3h (from 45.3±3.1 to 31.9±1.6 ng/mL) and stayed below the baseline at 5 h (35.9±2.2 ng/mL) (p < 0.0001 for both, compared to the baseline). Serum FFA decreased by 10 fold, reaching a nadir at 2h (from 0.611±0.033 to 0.067±0.004 mmol/L), then rebounded to 0.816±0.035 mmol/ L at 5h (p < 0.001 for both, compared to baseline). Both fasting-FABP4 and nadir-FABP4 correlated with obesity. Nadir-FABP4 correlated also with insulin resistance parameters from FS-IVGTT and with inflammation. Nadir-FFA, but not fasting-FFA, correlated with the METS-parameters. In conclusion, fasting-FABP4 related to metabolic risk markers more strongly than fasting-FFA. Nadir-FABP4 and nadir-FFA measured after glucose loading may provide better risk assessment than the fasting values. PMID:19394980

  13. Cell organelles from crassulacean acid metabolism (CAM) plants : II. Compartmentation of enzymes of the crassulacean acid metabolism.

    PubMed

    Schnarrenberger, C; Groß, D; Burkhard, C; Herbert, M

    1980-02-01

    The intracellular distribution of enzymes involved in the Crassulacean acid metabolism (CAM) has been studied in Bryophyllum calycinum Salisb. and Crassula lycopodioides Lam. After separation of cell organelles by isopycnic centrifugation, enzymes of the Crassulacean acid metabolism were found in the following cell fractions: Phosphoenolpyruvate carboxylase in the chloroplasts; NAD-dependent malate dehydrogenase in the mitochondria and in the supernatant; NADP-dependent malate dehydrogenase and phosphoenolpyruvate carboxykinase in the chloroplasts; NADP-dependent malic enzyme in the supernatant and to a minor extent in the chloroplasts; NAD-dependent malic enzyme in the supernatant and to some degree in the mitochondria; and pyruvate; orthophosphate dikinase in the chloroplasts. The activity of the NAD-dependent malate dehydrogenase was due to three isoenzymes separated by (NH4)2SO4 gradient solubilization. These isoenzymes represented 17, 78, and 5% of the activity recovered, respectively, in the order of elution. The isoenzyme eluting first was associated with the mitochondria and the second isoenzyme was of cytosolic origin, while the intracellular location of the third isoenzyme was probably the peroxisome. Based on these findings, the metabolic path of Crassulacean acid metabolism within cells of CAM plants is discussed.

  14. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    PubMed Central

    Noel, Olivier F.; Still, Christopher D.; Argyropoulos, George; Edwards, Michael; Gerhard, Glenn S.

    2016-01-01

    Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes. PMID:27006824

  15. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants.

    PubMed

    Yang, J C; Loewus, F A

    1975-08-01

    l-Ascorbic acid-1-(14)C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants.

  16. Metabolic Conversion of l-Ascorbic Acid to Oxalic Acid in Oxalate-accumulating Plants 1

    PubMed Central

    Yang, Joan C.; Loewus, Frank A.

    1975-01-01

    l-Ascorbic acid-1-14C and its oxidation product, dehydro-l-ascorbic acid, produced labeled oxalic acid in oxalate-accumulating plants such as spinach seedlings (Spinacia oleracea) and the detached leaves of woodsorrel (Oxalis stricta and O. oregana), shamrock (Oxalis adenopylla), and begonia (Begonia evansiana). In O. oregana, conversion occurred equally well in the presence or absence of light. This relationship between l-ascorbic acid metabolism and oxalic acid formation must be given careful consideration in attempts to explain oxalic accumulation in plants. PMID:16659288

  17. Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance.

    PubMed

    Meesapyodsuk, Dauenpen; Chen, Yan; Ng, Siew Hon; Chen, Jianan; Qiu, Xiao

    2015-11-01

    Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a "push" (synthesis) and "pull" (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fatty acid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses.

  18. Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism

    PubMed Central

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

    2017-01-01

    p,p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p’-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p’-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism.

  19. Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

    PubMed

    Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

    2017-01-01

    Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg(-1) SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

  20. Control of immune response by amino acid metabolism.

    PubMed

    Grohmann, Ursula; Bronte, Vincenzo

    2010-07-01

    The interaction between pathogenic microorganisms and their hosts is regulated by reciprocal survival strategies, including competition for essential nutrients. Though paradoxical, mammalian hosts have learned to take advantage of amino acid catabolism for controlling pathogen invasion and, at the same time, regulating their own immune responses. In this way, ancient catabolic enzymes have acquired novel functions and evolved into new structures with highly specialized functions, which go beyond the struggle for survival. In this review, we analyze the evidence supporting a critical role for the metabolism of various amino acids in regulating different steps of both innate and adaptive immunity.

  1. Metabolism of Cholesterol and Bile Acids by the Gut Microbiota

    PubMed Central

    Gérard, Philippe

    2013-01-01

    The human gastro-intestinal tract hosts a complex and diverse microbial community, whose collective genetic coding capacity vastly exceeds that of the human genome. As a consequence, the gut microbiota produces metabolites from a large range of molecules that host's enzymes are not able to convert. Among these molecules, two main classes of steroids, cholesterol and bile acids, denote two different examples of bacterial metabolism in the gut. Therefore, cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Moreover, this conversion occurs in a part of the human population only. Conversely, the primary bile acids (cholic and chenodeoxycholic acids) are converted to over twenty different secondary bile acid metabolites by the gut microbiota. The main bile salt conversions, which appear in the gut of the whole human population, include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation. If the metabolisms of cholesterol and bile acids by the gut microbiota are known for decades, their consequences on human health and disease are poorly understood and only start to be considered. PMID:25437605

  2. Metabolism of cholesterol and bile acids by the gut microbiota.

    PubMed

    Gérard, Philippe

    2013-12-30

    The human gastro-intestinal tract hosts a complex and diverse microbial community, whose collective genetic coding capacity vastly exceeds that of the human genome. As a consequence, the gut microbiota produces metabolites from a large range of molecules that host's enzymes are not able to convert. Among these molecules, two main classes of steroids, cholesterol and bile acids, denote two different examples of bacterial metabolism in the gut. Therefore, cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Moreover, this conversion occurs in a part of the human population only. Conversely, the primary bile acids (cholic and chenodeoxycholic acids) are converted to over twenty different secondary bile acid metabolites by the gut microbiota. The main bile salt conversions, which appear in the gut of the whole human population, include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation. If the metabolisms of cholesterol and bile acids by the gut microbiota are known for decades, their consequences on human health and disease are poorly understood and only start to be considered.

  3. D-lactic acid production by metabolically engineered Saccharomyces cerevisiae.

    PubMed

    Ishida, Nobuhiro; Suzuki, Tomiko; Tokuhiro, Kenro; Nagamori, Eiji; Onishi, Toru; Saitoh, Satoshi; Kitamoto, Katsuhiko; Takahashi, Haruo

    2006-02-01

    Poly D-lactic acid is an important polymer because it improves the thermostability of poly L-lactic acid by the stereo complex formation. We constructed a metabolically engineered Saccharomyces cerevisiae that produces D-lactic acid efficiently. In this recombinant, the coding region of pyruvate decarboxylase 1 (PDC1) was completely deleted, and two copies of the D-lactate dehydrogenase (D-LDH) gene from Leuconostoc mesenteroides subsp. mesenteroides strain NBRC3426 were introduced into the genome. The D-lactate production reached 61.5 g/l, the amount of glucose being transformed into D-lactic acid being 61.2% under neutralizing conditions. Additionally, the yield of free D-lactic acid was also shown to be 53.0% under non-neutralizing conditions. It was confirmed that D-lactic acid of extremely high optical purity of 99.9% or higher. Our finding obtained the possibility of a new approach for pure d-lactic acid production without a neutralizing process compared with other techniques involving lactic acid bacteria and transgenic Escherichia coli.

  4. Metabolic reprogramming by the pyruvate dehydrogenase kinase-lactic acid axis: Linking metabolism and diverse neuropathophysiologies.

    PubMed

    Jha, Mithilesh Kumar; Lee, In-Kyu; Suk, Kyoungho

    2016-09-01

    Emerging evidence indicates that there is a complex interplay between metabolism and chronic disorders in the nervous system. In particular, the pyruvate dehydrogenase (PDH) kinase (PDK)-lactic acid axis is a critical link that connects metabolic reprogramming and the pathophysiology of neurological disorders. PDKs, via regulation of PDH complex activity, orchestrate the conversion of pyruvate either aerobically to acetyl-CoA, or anaerobically to lactate. The kinases are also involved in neurometabolic dysregulation under pathological conditions. Lactate, an energy substrate for neurons, is also a recently acknowledged signaling molecule involved in neuronal plasticity, neuron-glia interactions, neuroimmune communication, and nociception. More recently, the PDK-lactic acid axis has been recognized to modulate neuronal and glial phenotypes and activities, contributing to the pathophysiologies of diverse neurological disorders. This review covers the recent advances that implicate the PDK-lactic acid axis as a novel linker of metabolism and diverse neuropathophysiologies. We finally explore the possibilities of employing the PDK-lactic acid axis and its downstream mediators as putative future therapeutic strategies aimed at prevention or treatment of neurological disorders.

  5. Maintenance Carbon Cycle in Crassulacean Acid Metabolism Plant Leaves 1

    PubMed Central

    Kenyon, William H.; Severson, Ray F.; Black, Clanton C.

    1985-01-01

    The reciprocal relationship between diurnal changes in organic acid and storage carbohydrate was examined in the leaves of three Crassulacean acid metabolism plants. It was found that depletion of leaf hexoses at night was sufficient to account quantitatively for increase in malate in Ananas comosus but not in Sedum telephium or Kalanchoë daigremontiana. Fructose and to a lesser extent glucose underwent the largest changes. Glucose levels in S. telephium leaves oscillated diurnally but were not reciprocally related to malate fluctuations. Analysis of isolated protoplasts and vacuoles from leaves of A. comosus and S. telephium revealed that vacuoles contain a large percentage (>50%) of the protoplast glucose, fructose and malate, citrate, isocitrate, ascorbate and succinate. Sucrose, a major constituent of intact leaves, was not detectable or was at extremely low levels in protoplasts and vacuoles from both plants. In isolated vacuoles from both A. comosus and S. telephium, hexose levels decreased at night at the same time malate increased. Only in A. comosus, however, could hexose metabolism account for a significant amount of the nocturnal increase in malate. We conclude that, in A. comosus, soluble sugars are part of the daily maintenance carbon cycle and that the vacuole plays a dynamic role in the diurnal carbon assimilation cycle of this Crassulacean acid metabolism plant. PMID:16664005

  6. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

    PubMed Central

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-01-01

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

  7. Ancestral genetic complexity of arachidonic acid metabolism in Metazoa.

    PubMed

    Yuan, Dongjuan; Zou, Qiuqiong; Yu, Ting; Song, Cuikai; Huang, Shengfeng; Chen, Shangwu; Ren, Zhenghua; Xu, Anlong

    2014-09-01

    Eicosanoids play an important role in inducing complex and crucial physiological processes in animals. Eicosanoid biosynthesis in animals is widely reported; however, eicosanoid production in invertebrate tissue is remarkably different to vertebrates and in certain respects remains elusive. We, for the first time, compared the orthologs involved in arachidonic acid (AA) metabolism in 14 species of invertebrates and 3 species of vertebrates. Based on parsimony, a complex AA-metabolic system may have existed in the common ancestor of the Metazoa, and then expanded and diversified through invertebrate lineages. A primary vertebrate-like AA-metabolic system via cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways was further identified in the basal chordate, amphioxus. The expression profiling of AA-metabolic enzymes and lipidomic analysis of eicosanoid production in the tissues of amphioxus supported our supposition. Thus, we proposed that the ancestral complexity of AA-metabolic network diversified with the different lineages of invertebrates, adapting with the diversity of body plans and ecological opportunity, and arriving at the vertebrate-like pattern in the basal chordate, amphioxus.

  8. Light quality modulates metabolic synchronization over the diel phases of crassulacean acid metabolism

    PubMed Central

    Ceusters, Johan; Borland, Anne M.; Taybi, Tahar; Frans, Mario; Godts, Christof; De Proft, Maurice P.

    2014-01-01

    Temporal compartmentation of carboxylation processes is a defining feature of crassulacean acid metabolism and involves circadian control of key metabolic and transport steps that regulate the supply and demand for carbon over a 24h cycle. Recent insights on the molecular workings of the circadian clock and its connection with environmental inputs raise new questions on the importance of light quality and, by analogy, certain photoreceptors for synchronizing the metabolic components of CAM. The present work tested the hypothesis that optimal coupling of stomatal conductance, net CO2 uptake, and the reciprocal turnover of carbohydrates and organic acids over the diel CAM cycle requires both blue and red light input signals. Contrasting monochromatic wavelengths of blue, green, and red light (i.e. 475, 530, 630nm) with low fluence rates (10 μmol m–2 s–1) were administered for 16 hours each diel cycle for a total treatment time of 48 hours to the obligate CAM bromeliad, Aechmea ‘Maya’. Of the light treatments imposed, low-fluence blue light was a key determinant in regulating stomatal responses, organic acid mobilization from the vacuole, and daytime decarboxylation. However, the reciprocal relationship between starch and organic acid turnover that is typical for CAM was uncoupled under low-fluence blue light. Under low-fluence red or green light, the diel turnover of storage carbohydrates was orchestrated in line with the requirements of CAM, but a consistent delay in acid consumption at dawn compared with plants under white or low-fluence blue light was noted. Consistent with the acknowledged influences of both red and blue light as input signals for the circadian clock, the data stress the importance of both red and blue-light signalling pathways for synchronizing the metabolic and physiological components of CAM over the day/night cycle. PMID:24803500

  9. Metabolic engineering of biocatalysts for carboxylic acids production

    PubMed Central

    Liu, Ping; Jarboe, Laura R.

    2012-01-01

    Fermentation of renewable feedstocks by microbes to produce sustainable fuels and chemicals has the potential to replace petrochemical-based production. For example, carboxylic acids produced by microbial fermentation can be used to generate primary building blocks of industrial chemicals by either enzymatic or chemical catalysis. In order to achieve the titer, yield and productivity values required for economically viable processes, the carboxylic acid-producing microbes need to be robust and well-performing. Traditional strain development methods based on mutagenesis have proven useful in the selection of desirable microbial behavior, such as robustness and carboxylic acid production. On the other hand, rationally-based metabolic engineering, like genetic manipulation for pathway design, has becoming increasingly important to this field and has been used for the production of several organic acids, such as succinic acid, malic acid and lactic acid. This review investigates recent works on Saccharomyces cerevisiae and Escherichia coli, as well as the strategies to improve tolerance towards these chemicals. PMID:24688671

  10. Acylation and metabolism of (n-6) fatty acids in hepatocytes

    SciTech Connect

    Voss, A.C.; Sprecher, H.

    1986-05-01

    Isolated hepatocytes (5 x 10/sup 6/ in 2ml) from chow fed rats were incubated from 20 to 60 min. with increasing concentrations of (1-/sup 14/C) labeled 18:2 (n-6), 18:3 (n-6) or 20:3 (n-6) to define optimum conditions for measuring acylation and metabolism to other (n-6) acids with subsequent incorporation into lipids. The triglycerides (TG) and phospholipids (PL) contained 157 and 80 nmols of 18:2 (n-6) and 6.0 and 6.1 nmols of other (n-6) acids, respectively, when cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) for 40 min. When cells were incubated with 0.3mM (1-/sup 14/C) 18:2 (n-6) plus 0.15 to 0.45mM 18:3 (n-6) or 20:3 (n-6), the metabolism of 18:2 (n-6) to other (n-6) acids was inhibited but not totally abolished. These results may suggest that (n-6) acid made from linoleate do not totally equilibrate with exogenous 18:3 (n-6) or 20:3 (n-6).

  11. Jacaric acid is rapidly metabolized to conjugated linoleic acid in rats.

    PubMed

    Kijima, Ryo; Honma, Taro; Ito, Junya; Yamasaki, Masao; Ikezaki, Aya; Motonaga, Chihiro; Nishiyama, Kazuo; Tsuduki, Tsuyoshi

    2013-01-01

    We have shown previously that jacaric acid (JA; 8c,10t,12c-18:3), which has a conjugated triene system, has a strong anti-tumor effect. However, the characteristics of absorption and metabolism of JA have yet to be determined in vivo, and the details of absorption and metabolism of JA in the small intestine are particularly unclear. This information is required for effective use of JA in humans. Therefore, in this study we examined absorption and metabolism of JA using cannulation of the thoracic duct in rats. Emulsions of two test oils, jacaranda seed oil and tung oil, which contain JA and α-eleostearic acid (α-ESA; 9c,11t,13t-18:3), respectively, were administered to rats and lymph from the thoracic duct was collected over 24 h. We examined the rate of absorption of JA and possible conversion to a conjugated linoleic acid (CLA)containing a conjugated diene system. The positional isomerism of the CLA produced by JA metabolism was determined using gas chromatography-electron impact/mass spectrometry. The rate of absorption and percentage conversion of JA were compared with those of α-ESA. We found that JA is rapidly absorbed and converted to a CLA in rats and that the percentage conversion of JA was lower than that of α-ESA. This is the first report on the absorption and metabolism of JA and this information may be important for application of JA as a functional food.

  12. The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

    PubMed Central

    Liang, Shuang; Zhou, Yuanpeng; Wang, Huijun; Qian, Yanyan; Ma, Duan; Tian, Weidong; Persaud-Sharma, Vishwani; Yu, Chen; Ren, Yunyun; Zhou, Shufeng; Li, Xiaotian

    2014-01-01

    Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid. PMID:24524080

  13. Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development

    PubMed Central

    Ni, Zhiyou; Lin, Lijin; Tang, Yi; Wang, Zhihui; Wang, Xun; Wang, Jin; Lv, Xiulan; Xia, Hui

    2017-01-01

    To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium ‘Hongdeng’), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit. PMID:28245268

  14. Altered Cholesterol and Fatty Acid Metabolism in Huntington Disease

    PubMed Central

    Block, Robert C.; Dorsey, E. Ray; Beck, Christopher A.; Brenna, J. Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease. PMID:20802793

  15. Altered cholesterol and fatty acid metabolism in Huntington disease.

    PubMed

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  16. Metabolic Relations between Methylxanthines and Methyluric Acids in Coffea L.

    PubMed

    Petermann, J B; Baumann, T W

    1983-12-01

    Metabolism of purine alkaloids in the leaves of Coffea dewevrei De Wild et Durand var excelsa Chev, Coffea liberica Bull ex Hiern and Coffea abeokutae Cramer was studied by analyzing leaf discs collected during vegetative development and by feeding the following radioactive tracers: [(14)C]theobromine, [(14)C]caffeine, and [(14)C]theacrine (1,3,7,9-tetramethyluric acid). Their principal metabolites were quantitatively and qualitatively determined. All three species convert the precursors to the same radioactive products, and proceed through the same four maturity stages characterized by the alkaloid accumulation pattern and by a particular transformation potency: (stage 1) young plant accumulating caffeine, transforms theobromine to caffeine; (stage 2) caffeine is gradually replaced by theacrine, theobromine and caffeine are converted to theacrine; (stage 3) theacrine disappears whereas liberine (O(2), 1,9-thrimethyluric acid) accumulates, theacrine is metabolized to liberine; (stage 4) branched-out plant containing liberine but no theacrine, caffeine is converted rapidly to liberine via theacrine. Methylliberine (O(2),1,7,9-tetramethyluric acid), presumably the direct precursor of liberine, is occasionally found in low concentrations at stage 3 and 4.The collective term ;liberio-excelsoid' introduced by geneticists for the numerous races or species of Pachycoffea is in accordance with the phytochemical equality found in this work.

  17. Ascorbic acid metabolism during sweet cherry (Prunus avium) fruit development.

    PubMed

    Liang, Dong; Zhu, Tingting; Ni, Zhiyou; Lin, Lijin; Tang, Yi; Wang, Zhihui; Wang, Xun; Wang, Jin; Lv, Xiulan; Xia, Hui

    2017-01-01

    To elucidate metabolism of ascorbic acid (AsA) in sweet cherry fruit (Prunus avium 'Hongdeng'), we quantified AsA concentration, cloned sequences involved in AsA metabolism and investigated their mRNA expression levels, and determined the activity levels of selected enzymes during fruit development and maturation. We found that AsA concentration was highest at the petal-fall period (0 days after anthesis) and decreased progressively during ripening, but with a slight increase at maturity. AsA did nevertheless continue to accumulate over time because of the increase in fruit fresh weight. Full-length cDNAs of 10 genes involved in the L-galactose pathway of AsA biosynthesis and 10 involved in recycling were obtained. Gene expression patterns of GDP-L-galactose phosphorylase (GGP2), L-galactono-1, 4-lactone dehydrogenase (GalLDH), ascorbate peroxidase (APX3), ascorbate oxidase (AO2), glutathione reductase (GR1), and dehydroascorbate reductase (DHAR1) were in accordance with the AsA concentration pattern during fruit development, indicating that genes involved in ascorbic acid biosynthesis, degradation, and recycling worked in concert to regulate ascorbic acid accumulation in sweet cherry fruit.

  18. [Dependence of metabolic fecal amino acids on the amino acid content of the feed. 1. Metabolic fecal amino acids of rats fed with maize].

    PubMed

    Krawielitzki, K; Schadereit, R; Völker, T; Reichel, K

    1981-07-01

    The amount of metabolic fecal amino acids (MFAA) in dependence on the amino acid intake was determined for graded maize rations with 15N-labelled rats and the quota of labelled endogenous amino acids in faeces was calculated according to the isotope dilution method. The excretion of amino acids and MFAA in faeces are described as functions of the amino acid intake for 17 amino acids and regressively calculated. For all 17 amino acids investigated, there was a more or less steep increase of MFAA according to an increasing amino acid intake. In contrast to MFAA in N-free feeding, MFAA in feeding with pure maize (16.5% crude protein) increase to the 2- to 4.5-fold value. The thesis of the constancy of the excretion of MFAA can consequently be no longer maintained. The true digestibility according to the conventional method is, on an average of all amino acids, 7.3 units below the one ascertained according to the 15N-isotope method. For the limiting amino acids lysine and threonine the difference is biggest (23 resp. 17 units). Tryptophane as first limiting amino acid could not be determined. The true digestibility of nearly all amino acids ascertained for maize according to the isotope method is above 90%. For the limiting amino acids the expenditure resp. the loss of endogenous amino acids is biggest.

  19. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment.

    PubMed

    Billi de Catabbi, Silvia C; Faletti, Alicia; Fuentes, Federico; San Martín de Viale, Leonor C; Cochón, Adriana C

    2005-04-15

    Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg(-1) body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porphyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and omega-OH/omega-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA2

  20. Study of nucleic acid metabolism in two astronauts

    NASA Astrophysics Data System (ADS)

    Szabó, L. D.; Keresztes, P.; Pallos, J. P.; Csató, E.; Predmerszky, T.

    During the last years data have evidenced that alteration in nucleic acid metabolism, expecially increased urinary excretion of modified nucleosides reflects physiological changes in living organism. In relation with the Soyuz-36-Salyut-6-Soyuz-35 mission in 1980 urinary nucleoside excretion of two astronauts /B.F., V.K./ were traced. Individual daily urine samples were collected for 4 days before starting and 6 days after landing and were analysed with improved analytical procedures /affinity chromatography, high performance liquid chromatography/. Levels of 1-methylinosine, 1-methylguanosine and N,2,2-dimethylguanosine in urine were determined. Thus recorded changes differ considerably at two astronauts. One of the /V.K./ excreted nucleosides normally, another /B.F./ showed increase to 200-400 % levels excretion of above nucleosides on the second day after landing. The peak values disappeared on the 3-6 days after. To interpret this phenomenon extreme factors of space-flight /weightlessness, stress, radiations, etc./ have to be taken into consideration. However, we attach importance to training of astronauts. During the last decade data have evidenced that alterations in the metabolism of nucleic acids especial increased urinary excretion of modified nucleosides reflects physiological and in some cases pathological changes in living organism /1, 2, 3/. In relation with the Soyuz-36-Salyut-6-Soyuz-35 mission urinary excretion of certain modified nucleosides of two astronauts /B.F. and V.K./ were measured. The aim of the measurements was: how the metabolism of transfer ribonucleic acids /tRNAs/ refering to cosmic flight, how it is reflected in urinary excretions of modified nucleosides. For these purposes we studied the excretion of methylguanosine, dimethylguanosine and methylinosine. These nucleosides are the normal minor components of tRNA.

  1. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

    SciTech Connect

    Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

    2011-08-15

    Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to {approx} 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research Highlights: > MCF-7/Adr cells showed decreases in cellular GSH

  2. Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: Advances and prospects.

    PubMed

    Yin, Xian; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian

    2015-11-01

    Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketoglutaric acid, succinic acid, fumaric acid, l-malic acid, and oxaloacetate, which are building-block chemicals with wide applications and huge markets. In this review, we summarize the synthesis pathways of these organic acids and review recent advances in metabolic engineering strategies that enhance organic acid production. We also propose further improvements for the production of organic acids with systems and synthetic biology-guided metabolic engineering strategies.

  3. Amino acid supplementation alters bone metabolism during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

    2005-01-01

    High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

  4. Metabolic interactions between vitamin A and conjugated linoleic acid.

    PubMed

    Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Ortiz, Berenice; Giordano, Elena; Belury, Martha A; Quadro, Loredana; Banni, Sebastiano

    2014-03-24

    Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

  5. Glycerol metabolism and bitterness producing lactic acid bacteria in cidermaking.

    PubMed

    Garai-Ibabe, G; Ibarburu, I; Berregi, I; Claisse, O; Lonvaud-Funel, A; Irastorza, A; Dueñas, M T

    2008-02-10

    Several lactic acid bacteria were isolated from bitter tasting ciders in which glycerol was partially removed. The degradation of glycerol via glycerol dehydratase pathway was found in 22 out of 67 isolates. The confirmation of glycerol degradation by this pathway was twofold: showing their glycerol dehydratase activity and detecting the presence of the corresponding gene by a PCR method. 1,3-propanediol (1,3-PDL) and 3-hydroxypropionic acid (3-HP) were the metabolic end-products of glycerol utilization, and the accumulation of the acrolein precursor 3-hydroxypropionaldehyde (3-HPA) was also detected in most of them. The strain identification by PCR-DGGE rpoB showed that Lactobacillus collinoides was the predominant species and only 2 belonged to Lactobacillus diolivorans. Environmental conditions conducting to 3-HPA accumulation in cidermaking were studied by varying the fructose concentration, pH and incubation temperature in L. collinoides 17. This strain failed to grow with glycerol as sole carbon source and the addition of fructose enhanced both growth and glycerol degradation. Regarding end-products of glycerol metabolism, 1,3-PDL was always the main end-product in all environmental conditions assayed, the only exception being the culture with 5.55 mM fructose, where equimolar amounts of 1,3-PDL and 3-HP were found. The 3-HPA was transitorily accumulated in the culture medium under almost all culture conditions, the degradation rate being notably slower at 15 degrees C. However, no disappearance of 3-HPA was found at pH 3.6, a usual value in cider making. After sugar exhaustion, L. collinoides 17 oxidated lactic acid and/or mannitol to obtain energy and these oxidations were accompanied by the removal of the toxic 3-HPA increasing the 1,3-PDL, 3-HP and acetic acid contents.

  6. Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence.

    PubMed

    Paczkowski, M; Schoolcraft, W B; Krisher, R L

    2014-10-01

    Fatty acid β-oxidation (FAO) is essential for oocyte maturation in mice. The objective of this study was to determine the effect of etomoxir (a FAO inhibitor; 100 μM), carnitine (1 mM), and palmitic acid (1 or 100 μM) during maturation on metabolism and gene expression of the oocyte and cumulus cells, and subsequent embryo development in the mouse. Carnitine significantly increased embryo development, while there was a decrease in development following maturation with 100 μM palmitic acid or etomoxir (P<0.05) treatment. Glucose consumption per cumulus-oocyte complex (COC) was decreased after treatment with carnitine and increased following etomoxir treatment (P<0.05). Intracellular oocyte lipid content was decreased after carnitine or etomoxir exposure (P<0.05). Abundance of Slc2a1 (Glut1) was increased after etomoxir treatment in the oocyte and cumulus cells (P<0.05), suggesting stimulation of glucose transport and potentially the glycolytic pathway for energy production when FAO is inhibited. Abundance of carnitine palmitoyltransferase 2 (Cpt2) tended to increase in oocytes (P=0.1) after treatment with 100 μM palmitic acid and in cumulus cells after exposure to 1 μM palmitic acid (P=0.07). Combined with carnitine, 1 μM palmitic acid increased the abundance of Acsl3 (P<0.05) and Cpt2 tended to increase (P=0.07) in cumulus cells, suggesting FAO was increased during maturation in response to stimulators and fatty acids. In conclusion, fatty acid and glucose metabolism are related to the mouse COC, as inhibition of FAO increases glucose consumption. Stimulation of FAO decreases glucose consumption and lipid stores, positively affecting subsequent embryo development, while an overabundance of fatty acid or reduced FAO negatively affects oocyte quality.

  7. Altered arachidonic acid metabolism and platelet size in atopic subjects

    SciTech Connect

    Audera, C.; Rocklin, R.; Vaillancourt, R.; Jakubowski, J.A.; Deykin, D.

    1988-03-01

    The release and metabolism of endogenous arachidonic acid (AA) in physiologically activated platelets obtained from 11 atopic patients with allergic rhinitis and/or asthma was compared to that of sex- and age-matched nonatopic controls. Prelabeled (/sup 3/H)AA platelets were stimulated with thrombin or collagen and the amount of free (/sup 3/H)AA and radiolabeled metabolites released were measured by high-performance liquid chromatography. The results obtained indicate that although the incorporation of (/sup 3/H)AA into platelet phospholipids and total release of /sup 3/H-radioactivity upon stimulation were comparable in the two groups, the percentage of /sup 3/H-radioactivity released from platelets as free AA was significantly lower (P less than 0.01) in the atopic group. The reduction in free (/sup 3/H)AA was accompanied by an increase (P less than 0.01) in the percentage of /sup 3/H-radioactivity released as cyclooxygenase products in atopic platelets (compared to nonatopic cells) after stimulation with 10 and 25 micrograms/ml collagen. The amount of platelet lipoxygenase product released was comparable between the two groups. Although the blood platelet counts were similar, the mean platelet volume was statistically higher (P less than 0.01) in the atopic group. These results indicate that arachidonic acid metabolism in atopic platelets is altered, the pathophysiological significance of which remains to be clarified.

  8. Polyunsaturated fatty acids in pregnancy and metabolic syndrome: a review.

    PubMed

    Poniedzialek-Czajkowska, Elzbieta; Mierzynski, Radzislaw; Kimber-Trojnar, Zaneta; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan

    2014-01-01

    This review presents available evidence for possible application of n-3 long chain polyunsaturated fatty acids (PUFAs) in pregnant obese women with metabolic syndrome (MS) and focuses on prophylaxis of pregnancy complications associated with MS such as gestational hypertension, preeclampsia and gestational diabetes. Dietary supplementation with n-3 PUFAs has recently become popular and their adequate intake during pregnancy and early childhood is of clinical importance. The results of experimental and epidemiological investigations reveal that n-3 PUFAs, especially α- linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), may decrease the risk of cardiovascular diseases. It is believed that n-3 PUFAs affect a multitude of molecular pathways, involving regulation of gene expression, alteration of physical and chemical properties of cellular membranes and modulation of membrane channels and proteins. A large body of evidence focuses on anti-inflammatory properties of PUFAs which seem to be fundamental in prevention and reversing of insulin resistance, atherogenic dyslipidemia, hypertension, thromboembolism and in improving vascular function. Despite the potential PUFAs benefits of decreasing insulin resistance, their application in order to prevent preeclampsia, gestational hypertension and gestational diabetes mellitus in pregnant women with MS has not yet been established. Numerous reports have revealed that appropriate fetal development, including neuronal, retinal and immune function depends on EPA and DHA which are crucial also for prevention of preterm birth. Thus the supplementation with EPA and DHA is highly recommended during pregnancy although the optimal dosing and treatment strategies still need to be determined.

  9. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

    PubMed Central

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  10. Defining meal requirements for protein to optimize metabolic roles of amino acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary protein provides essential amino acids (EAAs) for the synthesis of new proteins plus an array of other metabolic functions; many of these functions are sensitive to postprandial plasma and intracellular amino acid concentrations. Recent research has focused on amino acids as metabolic signal...

  11. Uncoupling effect of polyunsaturated fatty acid deficiency in isolated rat hepatocytes:effect on glycerol metabolism.

    PubMed Central

    Piquet, M A; Fontaine, E; Sibille, B; Filippi, C; Keriel, C; Leverve, X M

    1996-01-01

    The effects of a 4-week deficiency in polyunsaturated fatty acids (PUFA) in isolated rat hepatocytes have been investigated for oxidative phosphorylation and fatty acid, dihydroxyacetone (DHA) or glycerol metabolism. Oxygen uptake was significantly increased (by 20%) with or without fatty acid addition (octanoate or oleate) in the PUFA-deficient group compared with controls. The effect persisted after oligomycin addition but not after that of potassium cyanide, leading to the conclusion that, in these intact cells, the mitochondria were uncoupled. The PUFA-deficient group exhibited a significant decrease in the cytosolic ATP/ADP ratio, whereas the mitochondrial ratio was not affected. PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux. In contrast, glycerol metabolism was significantly enhanced in the PUFA-deficient group. The role of the glycerol 3-phosphate dehydrogenase step in this stimulation was evidenced in hepatocytes perifused with glycerol and octanoate in the presence of increased concentrations of 2,4-dinitrophenol (Dnp): uncoupling with Dnp led to an enhancement of glycerol metabolism, as found in PUFA deficiency, although it was more pronounced than in controls. The matrix/cytosol gradients for redox potential and ATP/ADP ratio were lower in cells from PUFA-deficient rats, suggesting a decreased mitochondrial membrane potential in accordance with the uncoupling effect. Moreover, a doubling of the mitochondrial glycerol 3-phosphate dehydrogenase activity in the PUFA-deficient group compared with controls led us to conclude that the activation of glycerol metabolism is the consequence of two mitochondrial effects: uncoupling and an increase in glycerol 3-phosphate dehydrogenase activity. PMID:8760348

  12. Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans

    PubMed Central

    Maruyama, Yukie; Oiki, Sayoko; Takase, Ryuichi; Mikami, Bunzo; Murata, Kousaku; Hashimoto, Wataru

    2015-01-01

    Glycosaminoglycans in mammalian extracellular matrices are degraded to their constituents, unsaturated uronic (glucuronic/iduronic) acids and amino sugars, through successive reactions of bacterial polysaccharide lyase and unsaturated glucuronyl hydrolase. Genes coding for glycosaminoglycan-acting lyase, unsaturated glucuronyl hydrolase, and the phosphotransferase system are assembled into a cluster in the genome of pathogenic bacteria, such as streptococci and clostridia. Here, we studied the streptococcal metabolic pathway of unsaturated uronic acids and the structure/function relationship of its relevant isomerase and dehydrogenase. Two proteins (gbs1892 and gbs1891) of Streptococcus agalactiae strain NEM316 were overexpressed in Escherichia coli, purified, and characterized. 4-Deoxy-l-threo-5-hexosulose-uronate (Dhu) nonenzymatically generated from unsaturated uronic acids was converted to 2-keto-3-deoxy-d-gluconate via 3-deoxy-d-glycero-2,5-hexodiulosonate through successive reactions of gbs1892 isomerase (DhuI) and gbs1891 NADH-dependent reductase/dehydrogenase (DhuD). DhuI and DhuD enzymatically corresponded to 4-deoxy-l-threo-5-hexosulose-uronate ketol-isomerase (KduI) and 2-keto-3-deoxy-d-gluconate dehydrogenase (KduD), respectively, involved in pectin metabolism, although no or low sequence identity was observed between DhuI and KduI or between DhuD and KduD, respectively. Genes for DhuI and DhuD were found to be included in the streptococcal genetic cluster, whereas KduI and KduD are encoded in clostridia. Tertiary and quaternary structures of DhuI and DhuD were determined by x-ray crystallography. Distinct from KduI β-barrels, DhuI adopts an α/β/α-barrel structure as a basic scaffold similar to that of ribose 5-phosphate isomerase. The structure of DhuD is unable to accommodate the substrate/cofactor, suggesting that conformational changes are essential to trigger enzyme catalysis. This is the first report on the bacterial metabolism of

  13. DIETARY N-6 POLYUNSATURATED FATTY ACID DEPRIVATION INCREASES DOCOSAHEXAENOIC ACID METABOLISM IN RAT BRAIN

    PubMed Central

    Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.

    2011-01-01

    Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A2 (cPLA2-IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective Ca2+-independent iPLA2-VIA expression. We hypothesized that these changes are accompanied by upregulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA “adequate” (31.4 wt% linoleic acid) or “deficient” (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-14C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acidn-3 (DPAn-3, 22:5n-3) and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid. Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promote neuroprotection. (199 words) PMID:22117540

  14. Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

    PubMed Central

    2010-01-01

    Background It has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism. Results Despite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes. Conclusion We identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems. PMID:20932325

  15. Conjugated linoleic acid isomers: differences in metabolism and biological effects.

    PubMed

    Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, Maria Puy

    2009-01-01

    The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis-9,trans-11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans-10,cis-12 isomer is more efficiently oxidized than the cis-9,trans-11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis-9,trans-11 and trans-10,cis-12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis-9,trans-11 isomer is mainly responsible for the anticarcinogenic effect, the trans-10,cis-12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently.

  16. Metabolic rates associated with membrane fatty acids in mice selected for increased maximal metabolic rate

    PubMed Central

    Wone, Bernard W. M.; Donovan, Edward R.; Cushman, John C.; Hayes, Jack P.

    2014-01-01

    Aerobic metabolism of vertebrates is linked to membrane fatty acid (FA) composition. Although the membrane pacemaker hypothesis posits that desaturation of FAs accounts for variation in resting or basal metabolic rate (BMR), little is known about the FA profiles that underpin variation in maximal metabolic rate (MMR). We examined membrane FA composition of liver and skeletal muscle in mice after seven generations of selection for increased MMR. In both liver and skeletal muscle, unsaturation index did not differ between control and high-MMR mice. We also examined membrane FA composition at the individual-level of variation. In liver, 18:0, 20:3 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In gastrocnemius muscle, 18:2 n-6, 20:4 n-6, and 22:6 n-3 FAs were significant predictors of MMR. In addition, muscle 16:1 n-7, 18:1 n-9, and 22:5 n-3 FAs were significant predictors of BMR, whereas no liver FAs were significant predictors of BMR. Our findings indicate that (i) individual variation in MMR and BMR appear to be linked to membrane FA composition in the skeletal muscle and liver, and (ii) FAs that differ between selected and control lines are involved in pathways that can affect MMR or BMR. PMID:23422919

  17. Metabolism of hydroxycinnamic acids and esters by Brettanomyces in different red wines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Depending on the cultivars and other factors, differing concentrations of hydroxycinnamic acids (caffeic, p-coumaric, and ferulic acids) and their corresponding tartaric acid esters (caftaric, coutaric, and fertaric acid, respectively) are found in red wines. Hydroxycinnamic acids are metabolized by...

  18. PROTEIN METABOLISM IN REGENERATING WOUND TISSUE: FUNCTION OF THE SULFUR AMINO ACIDS.

    DTIC Science & Technology

    PROTEINS, *TISSUES(BIOLOGY), METABOLISM, TISSUES(BIOLOGY), REGENERATION(ENGINEERING), WOUNDS AND INJURIES, TISSUES(BIOLOGY), TRACER STUDIES, METHIONINE, COLLAGEN, TYROSINE, BIOSYNTHESIS, AMINO ACIDS .

  19. Metabolism of sulfur amino acids in Saccharomyces cerevisiae.

    PubMed Central

    Thomas, D; Surdin-Kerjan, Y

    1997-01-01

    Sulfur amino acid biosynthesis in Saccharomyces cerevisiae involves a large number of enzymes required for the de novo biosynthesis of methionine and cysteine and the recycling of organic sulfur metabolites. This review summarizes the details of these processes and analyzes the molecular data which have been acquired in this metabolic area. Sulfur biochemistry appears not to be unique through terrestrial life, and S. cerevisiae is one of the species of sulfate-assimilatory organisms possessing a larger set of enzymes for sulfur metabolism. The review also deals with several enzyme deficiencies that lead to a nutritional requirement for organic sulfur, although they do not correspond to defects within the biosynthetic pathway. In S. cerevisiae, the sulfur amino acid biosynthetic pathway is tightly controlled: in response to an increase in the amount of intracellular S-adenosylmethionine (AdoMet), transcription of the coregulated genes is turned off. The second part of the review is devoted to the molecular mechanisms underlying this regulation. The coordinated response to AdoMet requires two cis-acting promoter elements. One centers on the sequence TCACGTG, which also constitutes a component of all S. cerevisiae centromeres. Situated upstream of the sulfur genes, this element is the binding site of a transcription activation complex consisting of a basic helix-loop-helix factor, Cbf1p, and two basic leucine zipper factors, Met4p and Met28p. Molecular studies have unraveled the specific functions for each subunit of the Cbf1p-Met4p-Met28p complex as well as the modalities of its assembly on the DNA. The Cbf1p-Met4p-Met28p complex contains only one transcription activation module, the Met4p subunit. Detailed mutational analysis of Met4p has elucidated its functional organization. In addition to its activation and bZIP domains, Met4p contains two regulatory domains, called the inhibitory region and the auxiliary domain. When the level of intracellular AdoMet increases

  20. Production of free monounsaturated fatty acids by metabolically engineered Escherichia coli

    PubMed Central

    2014-01-01

    Background Monounsaturated fatty acids (MUFAs) are the best components for biodiesel when considering the low temperature fluidity and oxidative stability. However, biodiesel derived from vegetable oils or microbial lipids always consists of significant amounts of polyunsaturated and saturated fatty acids (SFAs) alkyl esters, which hampers its practical applications. Therefore, the fatty acid composition should be modified to increase MUFA contents as well as enhancing oil and lipid production. Results The model microorganism Escherichia coli was engineered to produce free MUFAs. The fatty acyl-ACP thioesterase (AtFatA) and fatty acid desaturase (SSI2) from Arabidopsis thaliana were heterologously expressed in E. coli BL21 star(DE3) to specifically release free unsaturated fatty acids (UFAs) and convert SFAs to UFAs. In addition, the endogenous fadD gene (encoding acyl-CoA synthetase) was disrupted to block fatty acid catabolism while the native acetyl-CoA carboxylase (ACCase) was overexpressed to increase the malonyl coenzyme A (malonyl-CoA) pool and boost fatty acid biosynthesis. The finally engineered strain BL21ΔfadD/pE-AtFatAssi2&pA-acc produced 82.6 mg/L free fatty acids (FFAs) under shake-flask conditions and FFAs yield on glucose reached about 3.3% of the theoretical yield. Two types of MUFAs, palmitoleate (16:1Δ9) and cis-vaccenate (18:1Δ11) made up more than 75% of the FFA profiles. Fed-batch fermentation of this strain further enhanced FFAs production to a titer of 1.27 g/L without affecting fatty acid compositions. Conclusions This study demonstrated the possibility to regulate fatty acid composition by using metabolic engineering approaches. FFAs produced by the recombinant E. coli strain consisted of high-level MUFAs and biodiesel manufactured from these fatty acids would be more suitable for current diesel engines. PMID:24716602

  1. Metabolic Engineering of a Novel Muconic Acid Biosynthesis Pathway via 4-Hydroxybenzoic Acid in Escherichia coli

    PubMed Central

    Sengupta, Sudeshna; Goonewardena, Lakshani; Juturu, Veeresh

    2015-01-01

    cis,cis-Muconic acid (MA) is a commercially important raw material used in pharmaceuticals, functional resins, and agrochemicals. MA is also a potential platform chemical for the production of adipic acid (AA), terephthalic acid, caprolactam, and 1,6-hexanediol. A strain of Escherichia coli K-12, BW25113, was genetically modified, and a novel nonnative metabolic pathway was introduced for the synthesis of MA from glucose. The proposed pathway converted chorismate from the aromatic amino acid pathway to MA via 4-hydroxybenzoic acid (PHB). Three nonnative genes, pobA, aroY, and catA, coding for 4-hydroxybenzoate hydrolyase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase, respectively, were functionally expressed in E. coli to establish the MA biosynthetic pathway. E. coli native genes ubiC, aroFFBR, aroE, and aroL were overexpressed and the genes ptsH, ptsI, crr, and pykF were deleted from the E. coli genome in order to increase the precursors of the proposed MA pathway. The final engineered E. coli strain produced nearly 170 mg/liter of MA from simple carbon sources in shake flask experiments. The proposed pathway was proved to be functionally active, and the strategy can be used for future metabolic engineering efforts for production of MA from renewable sugars. PMID:26362984

  2. Cadmium Induces Retinoic Acid Signaling by Regulating Retinoic Acid Metabolic Gene Expression*

    PubMed Central

    Cui, Yuxia; Freedman, Jonathan H.

    2009-01-01

    The transition metal cadmium is an environmental teratogen. In addition, cadmium and retinoic acid can act synergistically to induce forelimb malformations. The molecular mechanism underlying the teratogenicity of cadmium and the synergistic effect with retinoic acid has not been addressed. An evolutionarily conserved gene, β,β-carotene 15,15′-monooxygenase (BCMO), which is involved in retinoic acid biosynthesis, was studied in both Caenorhabditis elegans and murine Hepa 1–6 cells. In C. elegans, bcmo-1 was expressed in the intestine and was cadmium inducible. Similarly, in Hepa 1–6 cells, Bcmo1 was induced by cadmium. Retinoic acid-mediated signaling increased after 24-h exposures to 5 and 10 μm cadmium in Hepa 1–6 cells. Examination of gene expression demonstrated that the induction of retinoic acid signaling by cadmium may be mediated by overexpression of Bcmo1. Furthermore, cadmium inhibited the expression of Cyp26a1 and Cyp26b1, which are involved in retinoic acid degradation. These results indicate that cadmium-induced teratogenicity may be due to the ability of the metal to increase the levels of retinoic acid by disrupting the expression of retinoic acid-metabolizing genes. PMID:19556237

  3. Quantitative metabolomics analysis of amino acid metabolism in recombinant Pichia pastoris under different oxygen availability conditions

    PubMed Central

    2012-01-01

    Background Environmental and intrinsic stress factors can result in the global alteration of yeast physiology, as evidenced by several transcriptional studies. Hypoxia has been shown to have a beneficial effect on the expression of recombinant proteins in Pichia pastoris growing on glucose. Furthermore, transcriptional profiling analyses revealed that oxygen availability was strongly affecting ergosterol biosynthesis, central carbon metabolism and stress responses, in particular the unfolded protein response. To contribute to the better understanding of the effect and interplay of oxygen availability and foreign protein secretion on central metabolism, a first quantitative metabolomic analysis of free amino acids pools in a recombinant P. pastoris strain growing under different oxygen availability conditions has been performed. Results The values obtained indicate significant variations in the intracellular amino acid pools due to different oxygen availability conditions, showing an overall increase of their size under oxygen limitation. Notably, even while foreign protein productivities were relatively low (about 40–80 μg Fab/gDCW·h), recombinant protein production was found to have a limited but significant impact on the intracellular amino acid pools, which were generally decreased in the producing strain compared with the reference strain. However, observed changes in individual amino acids pools were not correlated with their corresponding relative abundance in the recombinant protein sequence, but to the overall cell protein amino acid compositional variations. Conclusions Overall, the results obtained, combined with previous transcriptomic and proteomic analyses provide a systematic metabolic fingerprint of the oxygen availability impact on recombinant protein production in P. pastoris. PMID:22704468

  4. Phosphoenolpyruvate Carboxykinase in Plants Exhibiting Crassulacean Acid Metabolism 1

    PubMed Central

    Dittrich, P.; Campbell, Wilbur H.; Black, C. C.

    1973-01-01

    Phosphoenolpyruvate carboxykinase has been found in significant activities in a number of plants exhibiting Crassulacean acid metabolism. Thirty-five species were surveyed for phosphoenolpyruvate carboxykinase, phosphoenolpyruvate carboxylase, ribulose diphosphate carboxylase, malic enzyme, and malate dehydrogenase (NAD). Plants which showed high activities of malic enzyme contained no detectable phosphoenolpyruvate carboxykinase, while plants with high activities of the latter enzyme contained little malic enzyme. It is proposed that phosphoenolpyruvate carboxykinase acts as a decarboxylase during the light period, furnishing CO2 for the pentose cycle and phosphoenolpyruvate for gluconeogenesis. Some properties of phosphoenolpyruvate carboxykinase in crude extracts of pineapple leaves were investigated. The enzyme required Mn2+, Mg2+, and ATP for maximum activity. About 60% of the activity could be pelleted, along with chloroplasts and mitochondria, in extracts from leaves kept in the dark overnight. PMID:16658562

  5. Engineering crassulacean acid metabolism to improve water-use efficiency

    PubMed Central

    Borland, Anne M.; Hartwell, James; Weston, David J.; Schlauch, Karen A.; Tschaplinski, Timothy J.; Tuskan, Gerald A.; Yang, Xiaohan; Cushman, John C.

    2014-01-01

    Climatic extremes threaten agricultural sustainability worldwide. One approach to increase plant water-use efficiency is to introduce crassulacean acid metabolism (CAM) into C3 crops. Such a task requires comprehensive systems-level understanding of the enzymatic and regulatory pathways underpinning this temporal CO2 pump. Here, we review the progress that has been made in achieving this goal. Given that CAM arose through multiple independent evolutionary origins, comparative transcriptomics and genomics of taxonomically diverse CAM species are being used to define the genetic ‘parts list’ required to operate the core CAM functional modules of nocturnal carboxylation, daytime decarboxylation, and inverse stomatal regulation. Engineered CAM offers the potential to sustain plant productivity for food, feed, fiber, and biofuel production in hotter and drier climates. PMID:24559590

  6. Engineering crassulacean acid metabolism to improve water-use efficiency.

    PubMed

    Borland, Anne M; Hartwell, James; Weston, David J; Schlauch, Karen A; Tschaplinski, Timothy J; Tuskan, Gerald A; Yang, Xiaohan; Cushman, John C

    2014-05-01

    Climatic extremes threaten agricultural sustainability worldwide. One approach to increase plant water-use efficiency (WUE) is to introduce crassulacean acid metabolism (CAM) into C3 crops. Such a task requires comprehensive systems-level understanding of the enzymatic and regulatory pathways underpinning this temporal CO2 pump. Here we review the progress that has been made in achieving this goal. Given that CAM arose through multiple independent evolutionary origins, comparative transcriptomics and genomics of taxonomically diverse CAM species are being used to define the genetic 'parts list' required to operate the core CAM functional modules of nocturnal carboxylation, diurnal decarboxylation, and inverse stomatal regulation. Engineered CAM offers the potential to sustain plant productivity for food, feed, fiber, and biofuel production in hotter and drier climates.

  7. How does fish metamorphosis affect aromatic amino acid metabolism?

    PubMed

    Pinto, Wilson; Figueira, Luís; Dinis, Maria Teresa; Aragão, Cláudia

    2009-02-01

    Aromatic amino acids (AAs, phenylalanine and tyrosine) may be specifically required during fish metamorphosis, since they are the precursors of thyroid hormones which regulate this process. This project attempted to evaluate aromatic AA metabolism during the ontogenesis of fish species with a marked (Senegalese sole; Solea senegalensis) and a less accentuated metamorphosis (gilthead seabream; Sparus aurata). Fish were tube-fed with three L-[U-14C] AA solutions at pre-metamorphic, metamorphic and post-metamorphic stages of development: controlled AA mixture (Mix), phenylalanine (Phe) and tyrosine (Tyr). Results showed a preferential aromatic AA retention during the metamorphosis of Senegalese sole, rather than in gilthead seabream. Senegalese sole's highly accentuated metamorphosis seems to increase aromatic AA physiological requirements, possibly for thyroid hormone production. Thus, Senegalese sole seems to be especially susceptible to dietary aromatic AA deficiencies during the metamorphosis period, and these findings may be important for physiologists, fish nutritionists and the flatfish aquaculture industry.

  8. Microbial diversity and metabolic networks in acid mine drainage habitats

    PubMed Central

    Méndez-García, Celia; Peláez, Ana I.; Mesa, Victoria; Sánchez, Jesús; Golyshina, Olga V.; Ferrer, Manuel

    2015-01-01

    Acid mine drainage (AMD) emplacements are low-complexity natural systems. Low-pH conditions appear to be the main factor underlying the limited diversity of the microbial populations thriving in these environments, although temperature, ionic composition, total organic carbon, and dissolved oxygen are also considered to significantly influence their microbial life. This natural reduction in diversity driven by extreme conditions was reflected in several studies on the microbial populations inhabiting the various micro-environments present in such ecosystems. Early studies based on the physiology of the autochthonous microbiota and the growing success of omics-based methodologies have enabled a better understanding of microbial ecology and function in low-pH mine outflows; however, complementary omics-derived data should be included to completely describe their microbial ecology. Furthermore, recent updates on the distribution of eukaryotes and archaea recovered through sterile filtering (herein referred to as filterable fraction) in these environments demand their inclusion in the microbial characterization of AMD systems. In this review, we present a complete overview of the bacterial, archaeal (including filterable fraction), and eukaryotic diversity in these ecosystems, and include a thorough depiction of the metabolism and element cycling in AMD habitats. We also review different metabolic network structures at the organismal level, which is necessary to disentangle the role of each member of the AMD communities described thus far. PMID:26074887

  9. Effects of niflumic acid on polyphosphoinositide and oxidative metabolism in polymorphonuclear leukocytes from healthy and thermally injured rats.

    PubMed

    Tissot, M; Roch-Arveiller, M; Fontagne, J; Giroud, J P

    1992-12-01

    Thermal injury in rats leads to an impairment of polymorphonuclear leukocyte (PMN) functions, particularly oxidative metabolism and phosphoinositide turnover. As prostaglandin E2, which has immunosuppressive properties, is released in high levels after burn trauma, we investigated the in vitro and in vivo effects of a nonsteroidal antiinflammatory drug, niflumic acid, on oxidative and phosphoinositide metabolism in PMNs from healthy and burned rats. Given the role of fluoride ions on PMN, the influence of niflumic acid was compared with that of sodium fluoride (NaF) at equivalent doses of F-. In vitro, niflumic acid and sodium fluoride had no effect on oxidative metabolism in stimulated by formyl methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ) or nonstimulated PMNs from healthy and burned rats. Niflumic acid slightly increased the production of inositol phosphate by nonstimulated PMNs from healthy and burned rats. Niflumic acid and NaF partly restored the stimulating effect of FMLP on inositol phosphate production by PMNs from burned rats. In vivo treatment with niflumic acid and NaF increased the oxidative metabolism of PMNs from burned rats but not healthy rats. Niflumic acid, more than NaF, restored the activity of both stimulants on phosphoinositide metabolism in PMNs from burned rats. In conclusion, at non-antiinflammatory doses, while inhibiting cyclooxygenase activity, niflumic acid exerts a complex effect on the burn-induced depression of PMN functions. The fluoride anion induces similar but generally weaker effects and seems to be involved in the restoring effects of niflumic acid on PMN functions in burned rats.

  10. Repurposing Resveratrol and Fluconazole To Modulate Human Cytochrome P450-Mediated Arachidonic Acid Metabolism.

    PubMed

    El-Sherbeni, Ahmed A; El-Kadi, Ayman O S

    2016-04-04

    Cytochrome P450 (P450) enzymes metabolize arachidonic acid (AA) to several biologically active epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Repurposing clinically-approved drugs could provide safe and readily available means to control EETs and HETEs levels in humans. Our aim was to determine how to significantly and selectively modulate P450-AA metabolism in humans by clinically-approved drugs. Liquid chromatography-mass spectrometry was used to determine the formation of 15 AA metabolites by human recombinant P450 enzymes, as well as human liver and kidney microsomes. CYP2C19 showed the highest EET-forming activity, while CYP1B1 and CYP2C8 showed the highest midchain HETE-forming activities. CYP1A1 and CYP4 showed the highest subterminal- and 20-HETE-forming activity, respectively. Resveratrol and fluconazole produced the most selective and significant modulation of hepatic P450-AA metabolism, comparable to investigational agents. Monte Carlo simulations showed that 90% of human population would experience a decrease by 6-22%, 16-39%, and 16-35% in 16-, 18-, and 20-HETE formation, respectively, after 2.5 g daily of resveratrol, and by 22-31% and 14-23% in 8,9- and 14,15-EET formation after 50 mg of fluconazole. In conclusion, clinically-approved drugs can provide selective and effective means to modulate P450-AA metabolism, comparable to investigational drugs. Resveratrol and fluconazole are good candidates to be repurposed as new P450-based treatments.

  11. Uric acid in metabolic syndrome: From an innocent bystander to a central player

    PubMed Central

    Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

    2016-01-01

    Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

  12. Relationships between Arachidonic Acid, Uterine Activity and Metabolic Regulation of Placental Lactogen Secretion.

    DTIC Science & Technology

    1982-08-01

    variations and to determine the metabolic role of oPL during gestation. Fasting, which decreased plasma glucose and increased plasma free fatty acid ... fatty acids induced by fasting or to have diabetogenic effects. The intravenous administration of 12.5 or 25 mg of arachidonic acid resulted in a...of hPL is thought to be controlled by the plasma con- centrations of the metabolic substrates; carbohydrate, fat or protein. Plasma free fatty acid

  13. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats.

    PubMed

    Pakdeechote, Poungrat; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Prachaney, Parichat; Khrisanapant, Wilaiwan; Kukongviriyapan, Veerapol

    2014-01-16

    Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p<0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p<0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p<0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  14. Omega-3 polyunsaturated fatty acids and oxygenated metabolism in atherothrombosis.

    PubMed

    Guichardant, Michel; Calzada, Catherine; Bernoud-Hubac, Nathalie; Lagarde, Michel; Véricel, Evelyne

    2015-04-01

    Numerous epidemiological studies and clinical trials have reported the health benefits of omega-3 polyunsaturated fatty acids (PUFA), including a lower risk of coronary heart diseases. This review mainly focuses on the effects of alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on some risk factors associated with atherothrombosis, including platelet activation, plasma lipid concentrations and oxidative modification of low-density lipoproteins (LDL). Special focus is given to the effects of marine PUFA on the formation of eicosanoids and docosanoids, and to the bioactive properties of some oxygenated metabolites of omega-3 PUFA produced by cyclooxygenases and lipoxygenases. The antioxidant effects of marine omega-3 PUFA at low concentrations and the pro-oxidant effects of DHA at high concentrations on the redox status of platelets and LDL are highlighted. Non enzymatic peroxidation end-products deriving from omega-3 PUFA such as hydroxy-hexenals, neuroketals and EPA-derived isoprostanes are also considered in relation to atherosclerosis. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

  15. Leptin and uric acid as predictors of metabolic syndrome in jordanian adults

    PubMed Central

    Ahmad, Mousa N.; Haddad, Fares H.; Azzeh, Firas S.

    2016-01-01

    BACKGROUND/OBJECTIVES Metabolic syndrome (MetS) is a set of interrelated metabolic risk factors that increase the risk of cardiovascular morbidity and mortality. Studies regarding the specificity and sensitivity of serum levels of leptin and uric acid as predictors of MetS are limited. The aim of this study was to evaluate the serum levels of leptin and uric acid in terms of their specificity and sensitivity as predictors of MetS in the studied Jordanian group. SUBJECTS/METHODS In this cross sectional study, 630 adult subjects (308 men and 322 women) were recruited from the King Hussein Medical Center (Amman, Jordan). The diagnosis of MetS was made according to the 2005 International Diabetes Federation criteria. Receiver operating characteristic curves were used to determine the efficacy of serum levels of leptin and uric acid as predictors of MetS in the studied Jordanian group. RESULTS Study results showed that for identification of subjects with MetS risk, area under the curve (AUC) for leptin was 0.721 and 0.683 in men and women, respectively. Serum uric acid levels in men showed no significant association with any MetS risk factors and no significant AUC, while uric acid AUC was 0.706 in women. CONCLUSION Serum leptin levels can be useful biomarkers for evaluation of the risk of MetS independent of baseline obesity in both men and women. On the other hand, serum uric acid levels predicted the risk of MetS only in women. PMID:27478548

  16. CO(2)-concentrating: consequences in crassulacean acid metabolism.

    PubMed

    Lüttge, Ulrich

    2002-11-01

    The consequences of CO(2)-concentrating in leaf air-spaces of CAM plants during daytime organic acid decarboxylation in Phase III of CAM (crassulacean acid metabolism) are explored. There are mechanistic consequences of internal CO(2) partial pressures, p(i)(CO(2)). These are (i) effects on stomata, i.e. high p(i)(CO(2)) eliciting stomatal closure in Phase III, (ii) regulation of malic acid remobilization from the vacuole, malate decarboxylation and refixation of CO(2) via Rubisco (ribulose bisphosphate carboxylase/oxygenase), and (iii) internal signalling functions during the transitions between Phases II and III and III and IV, respectively, in the natural day/night cycle and in synchronizing the circadian clocks of individual leaf cells or leaf patches in the free-running endogenous rhythmicity of CAM. There are ecophysiological consequences. Obvious beneficial ecophysiological consequences are (i) CO(2)-acquisition, (ii) increased water-use- efficiency, (iii) suppressed photorespiration, and (iv) reduced oxidative stress by over-energization of the photosynthetic apparatus. However, the general potency of these beneficial effects may be questioned. There are also adverse ecophysiological consequences. These are (i) energetics, (ii) pH effects and (iii) Phase III oxidative stress. A major consequence of CO(2)-concentrating in Phase III is O(2)-concentrating, increased p(i)(CO(2)) is accompanied by increased p(i)(O(2)). Do reversible shifts of C(3)/CAM-intermediate plants between the C(3)-CAM-C(3) modes of photosynthesis indicate that C(3)-photosynthesis provides better protection from irradiance stress? There are many open questions and CAM remains a curiosity.

  17. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    PubMed Central

    Balaban, Seher; Lee, Lisa S.; Schreuder, Mark; Hoy, Andrew J.

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  18. Metabolic pathways regulated by abscisic acid, salicylic acid and γ-aminobutyric acid in association with improved drought tolerance in creeping bentgrass (Agrostis stolonifera).

    PubMed

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2017-01-01

    Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA.

  19. Beyond lipids, pharmacological PPARalpha activation has important effects on amino acid metabolism as studied in the rat.

    PubMed

    Sheikh, Kashif; Camejo, Germán; Lanne, Boel; Halvarsson, Torbjörn; Landergren, Marie Rydén; Oakes, Nicholas D

    2007-04-01

    PPARalpha agonists have been characterized largely in terms of their effects on lipids and glucose metabolism, whereas little has been reported about effects on amino acid metabolism. We studied responses to the PPARalpha agonist WY 14,643 (30 micromol x kg(-1) x day(-1) for 4 wk) in rats fed a saturated fat diet. Plasma and urine were analyzed with proton NMR. Plasma amino acids were measured using HPLC, and hepatic gene expression was assessed with DNA arrays. The high-fat diet elevated plasma levels of insulin and triglycerides (TG), and WY 14,643 treatment ameliorated this insulin resistance and dyslipidemia, lowering plasma insulin and TG levels. In addition, treatment decreased body weight gain, without altering cumulative food intake, and increased liver mass. WY 14,643 increased plasma levels of 12 of 22 amino acids, including glucogenic and some ketogenic amino acids, whereas arginine was significantly decreased. There was no alteration in branched-chain amino acid levels. Compared with the fat-fed control animals, WY 14,643-treated animals had raised plasma urea and ammonia levels as well as raised urine levels of N-methylnicotinamide and dimethylglycine. WY 14,643 induced changes in a number of key genes involved in amino acid metabolism in addition to expected effects on hepatic genes involved in lipid catabolism and ketone body formation. In conclusion, the present results suggest that, in rodents, effects of pharmacological PPARalpha activation extend beyond control of lipid metabolism to include important effects on whole body amino acid mobilization and hepatic amino acid metabolism.

  20. Metabolism of nonesterified and esterified hydroxycinnamic acids in red wines by Brettanomyces bruxellensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While Brettanomyces can metabolize non–esterified hydroxycinnamic acids found in grape musts/wines (caffeic, p–coumaric, and ferulic acids), it was not known whether this yeast could utilize the corresponding tartaric acid esters (caftaric, p–coutaric, and fertaric acids, respectively). Red wines fr...

  1. Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes.

    PubMed

    Ow, Yin-Yin; Stupans, Ieva

    2003-06-01

    Gallic acid and its structurally related compounds are found widely distributed in fruits and plants. Gallic acid, and its catechin derivatives are also present as one of the main phenolic components of both black and green tea. Esters of gallic acid have a diverse range of industrial uses, as antioxidants in food, in cosmetics and in the pharmaceutical industry. In addition, gallic acid is employed as a source material for inks, paints and colour developers. Studies utilising these compounds have found them to possess many potential therapeutic properties including anti-cancer and antimicrobial properties. In this review, studies of the effects of gallic acid, its esters, and gallic acid catechin derivatives on Phase I and Phase II enzymes are examined. Many published reports of the effects of the in vitro effects of gallic acid and its derivatives on drug metabolising enzymes concern effects directly on substrate (generally drug or mutagen) metabolism or indirectly through observed effects in Ames tests. In the case of the Ames test an antimutagenic effect may be observed through inhibition of CYP activation of indirectly acting mutagens and/or by scavenging of metabolically generated mutagenic electrophiles. There has been considerable interest in the in vivo effects of the gallate esters because of their incorporation into foodstuffs as antioxidants and in the catechin gallates with their potential role as chemoprotective agents. Principally an induction of Phase II enzymes has been observed however more recent studies using HepG2 cells and primary cultures of human hepatocytes provide evidence for the overall complexity of actions of individual components versus complex mixtures, such as those in food. Further systematic studies of mechanisms of induction and inhibition of drug metabolising enzymes by this group of compounds are warranted in the light of their distribution and consequent ingestion, current uses and suggested therapeutic potential. However, it

  2. Uric acid concentration in subjects at risk of type 2 diabetes mellitus: relationship to components of the metabolic syndrome.

    PubMed

    Costa, A; Igualá, I; Bedini, J; Quintó, L; Conget, I

    2002-03-01

    High uric acid concentration is a common finding in subjects with risk factors for cardiovascular disease (CVD), including some characteristics of the metabolic syndrome. However, its exact role in this setting and in the progression to type 2 diabetes mellitus (DM) is not well understood and could be affected by confounding factors such as hypertriglyceridemia. Our study aimed to establish the relationship between uric acid (avoiding the interference of high triglyceride levels), insulin sensitivity, and components of the metabolic syndrome in a group of subjects at high risk of developing DM. Among 201 subjects included in the study, 111 (55.2%) showed an abnormal oral glucose tolerance and uric acid levels higher than those measured in subjects with normal glucose tolerance. Body mass index (BMI), triglycerides, diastolic blood pressure (DBP), and 2-hour glycemia in the oral glucose tolerance test (OGTT) contributed independently to uric acid concentration (R2 =.59). However, uric acid did not affect either insulin sensitivity or glucose tolerance. The recovery tests revealed that a triglyceride concentration > or = 3 mmol/L interfered with the measurement of uric acid level when a colorimetric method was used, but not when a dry-chemistry method was used. In conclusion, uric acid concentration is higher in subjects at high risk of DM with abnormal glucose tolerance and is independently determined by various components of the metabolic syndrome.

  3. Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults

    PubMed Central

    Mozaffarian, Dariush; Cao, Haiming; King, Irena B.; Lemaitre, Rozenn N.; Song, Xiaoling; Siscovick, David S.; Hotamisligil, Gökhan S.

    2011-01-01

    independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. Limitations Measurement error; residual confounding. Conclusions Circulating trans-palmitoleate is associated with lower insulin resistance, atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support need for detailed further experimental and clinical investigation. Primary Funding Source National Institutes of Health. PMID:21173413

  4. Metabolism of Cyclohexane Carboxylic Acid by Alcaligenes Strain W1

    PubMed Central

    Taylor, David G.; Trudgill, Peter W.

    1978-01-01

    Thirty-three microorganisms capable of growth with cyclohexane carboxylate as the sole source of carbon were isolated from mud, water, and soil samples from the Aberystwyth area. Preliminary screening and whole-cell oxidation studies suggested that, with one exception, all of the strains metabolized the growth substrate by beta-oxidation of the coenzyme A ester. This single distinctive strain, able to oxidize rapidly trans-4-hydroxycyclohexane carboxylate, 4-ketocyclohexane carboxylate, p-hydroxybenzoate, and protocatechuate when grown with cyclohexane carboxylate, was classified as a strain of Alcaligenes and given the number W1. Enzymes capable of converting cyclohexane carboxylate to p-hydroxybenzoate were induced by growth with the alicyclic acid and included the first unambiguous specimen of a cyclohexane carboxylate hydroxylase. Because it is a very fragile protein, attempts to stabilize the cyclohexane carboxylate hydroxylase so that a purification procedure could be developed have consistently failed. In limited studies with crude cell extracts, we found that hydroxylation occurred at the 4 position, probably yielding the trans isomer of 4-hydroxycyclohexane carboxylate. Simultaneous measurement of oxygen consumption and reduced nicotinamide adenine dinucleotide oxidation, coupled with an assessment of reactant stoichiometry, showed the enzyme to be a mixed-function oxygenase. Mass spectral analysis enabled the conversion of cyclohexane carboxylate to p-hydroxybenzoate by cell extracts to be established unequivocally, and all of our data were consistent with the pathway: cyclohexane carboxylate → trans-4-hydroxycyclohexane carboxylate → 4-ketocyclohexane carboxylate → p-hydroxybenzoate. The further metabolism of p-hydroxybenzoate proceeded by meta fission and by the oxidative branch of the 2-hydroxy-4-carboxymuconic semialde-hyde-cleaving pathway. PMID:207665

  5. Arachidonic Acid and Eicosapentaenoic Acid Metabolism in Juvenile Atlantic Salmon as Affected by Water Temperature

    PubMed Central

    Norambuena, Fernando; Morais, Sofia; Emery, James A.; Turchini, Giovanni M.

    2015-01-01

    Salmons raised in aquaculture farms around the world are increasingly subjected to sub-optimal environmental conditions, such as high water temperatures during summer seasons. Aerobic scope increases and lipid metabolism changes are known plasticity responses of fish for a better acclimation to high water temperature. The present study aimed at investigating the effect of high water temperature on the regulation of fatty acid metabolism in juvenile Atlantic salmon fed different dietary ARA/EPA ratios (arachidonic acid, 20:4n-6/ eicosapentaenoic acid, 20:5n-3), with particular focus on apparent in vivo enzyme activities and gene expression of lipid metabolism pathways. Three experimental diets were formulated to be identical, except for the ratio EPA/ARA, and fed to triplicate groups of Atlantic salmon (Salmo salar) kept either at 10°C or 20°C. Results showed that fatty acid metabolic utilisation, and likely also their dietary requirements for optimal performance, can be affected by changes in their relative levels and by environmental temperature in Atlantic salmon. Thus, the increase in temperature, independently from dietary treatment, had a significant effect on the β-oxidation of a fatty acid including EPA, as observed by the apparent in vivo enzyme activity and mRNA expression of pparα -transcription factor in lipid metabolism, including β-oxidation genes- and cpt1 -key enzyme responsible for the movement of LC-PUFA from the cytosol into the mitochondria for β-oxidation-, were both increased at the higher water temperature. An interesting interaction was observed in the transcription and in vivo enzyme activity of Δ5fad–time-limiting enzyme in the biosynthesis pathway of EPA and ARA. Such, at lower temperature, the highest mRNA expression and enzyme activity was recorded in fish with limited supply of dietary EPA, whereas at higher temperature these were recorded in fish with limited ARA supply. In consideration that fish at higher water temperature

  6. Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

    PubMed Central

    2010-01-01

    Background Clostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed. Results C. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms. Conclusions Analysis of the C. sticklandii genome and

  7. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants)

    SciTech Connect

    Loewus, F.A. . Inst. of Biological Chemistry); Seib, P.A. . Dept. of Grain Science and Industry)

    1991-01-01

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  8. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants). Final report

    SciTech Connect

    Loewus, F.A.; Seib, P.A.

    1991-12-31

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  9. Rat liver microsomal lipid peroxidation produced during the oxidative metabolism of ethacrynic acid.

    PubMed

    Yamamoto, K; Masubuchi, Y; Narimatsu, S; Kobayashi, S; Horie, T

    2001-04-01

    Thiobarbituric acid reactive substances (TBARS) were produced in rat liver microsomal suspension incubated with ethacrynic acid (loop diuretic drug) and NADPH. Two oxidative metabolites of ethacrynic acid with dicarboxylic acid and hydroxylated ethyl group, respectively, were formed in the reaction mixture. The oxidative metabolism of ethacrynic acid was inhibited by cytochrome P450 inhibitors. The formation of TBARS was remarkably depressed by inhibitors like diethyldithiocarbamate and disulfiram. These results indicate that lipid peroxidation occurred in rat liver microsomes through the oxidative metabolism of ethacrynic acid.

  10. Interorgan ammonia and amino acid metabolism in metabolically stable patients with cirrhosis and a TIPSS.

    PubMed

    Olde Damink, Steven W M; Jalan, Rajiv; Redhead, Doris N; Hayes, Peter C; Deutz, Nicolaas E P; Soeters, Peter B

    2002-11-01

    Ammonia is central to the pathogenesis of hepatic encephalopathy. This study was designed to determine the quantitative dynamics of ammonia metabolism in patients with cirrhosis and previous treatment with a transjugular intrahepatic portosystemic stent shunt (TIPSS). We studied 24 patients with cirrhosis who underwent TIPSS portography. Blood was sampled and blood flows were measured across portal drained viscera, leg, kidney, and liver, and arteriovenous differences across the spleen and the inferior and superior mesenteric veins. The highest amount of ammonia was produced by the portal drained viscera. The kidneys also produced ammonia in amounts that equaled total hepatosplanchnic area production. Skeletal muscle removed more ammonia than the cirrhotic liver. The amount of nitrogen that was taken up by muscle in the form of ammonia was less than the glutamine that was released. The portal drained viscera consumed glutamine and produced ammonia, alanine, and citrulline. Urea was released in the splenic and superior mesenteric vein, contributing to whole-body ureagenesis in these cirrhotic patients. In conclusion, hyperammonemia in metabolically stable, overnight-fasted patients with cirrhosis of the liver and a TIPSS results from portosystemic shunting and renal ammonia production. Skeletal muscle removes more ammonia from the circulation than the cirrhotic liver. Muscle releases excessive amounts of the nontoxic nitrogen carrier glutamine, which can lead to ammonia production in the portal drained viscera (PDV) and kidneys. Urinary ammonia excretion and urea synthesis appear to be the only way to remove ammonia from the body.

  11. The central role of chloride in the metabolic acid-base changes in canine parvoviral enteritis.

    PubMed

    Burchell, Richard K; Schoeman, Johan P; Leisewitz, Andrew L

    2014-04-01

    The acid-base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid-base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid-base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson-Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid-base changes, according to the SIM, was chloride (P<0.001). Severely-affected animals tended to demonstrate hypochloraemic alkalosis, whereas mildly-affected puppies had a hyperchloraemic acidosis (P=0.007). In conclusion, the acid-base disturbances in CPV enteritis are multifactorial and complex, with the SIM providing information in terms of the origin of these changes.

  12. Gut microbiota of mice putatively modifies amino acid metabolism in the host brain.

    PubMed

    Kawase, Takahiro; Nagasawa, Mao; Ikeda, Hiromi; Yasuo, Shinobu; Koga, Yasuhiro; Furuse, Mitsuhiro

    2017-04-10

    Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age. Similar patterns were observed for the concentrations of l-Asp in striatum, cerebral cortex and hippocampus, and l-arginine (l-Arg), l-Ala and l-valine (l-Val) in striatum. In addition, the concentrations of l-Asp, d-Ala, l-histidine, l-isoleucine (l-Ile), l-leucine (l-Leu), l-phenylalanine and l-Val were significantly higher in plasma of SPF mice when compared with those of GF mice. The concentrations of l-Arg, l-Gln, l-Ile and l-Leu were significantly higher in SPF than in GF mice, but those of d-Asp, d-serine and l-serine were higher in some brain regions of GF mice than in those of SPF mice. In conclusion, the concentration of amino acids in the host brain seems to be dependent on presence of the gut microbiota. Amino acid metabolism in the host brain may be modified by manipulating microbiota communities.

  13. Therapeutic paracetamol treatment in older persons induces dietary and metabolic modifications related to sulfur amino acids.

    PubMed

    Pujos-Guillot, Estelle; Pickering, Gisèle; Lyan, Bernard; Ducheix, Gilles; Brandolini-Bunlon, Marion; Glomot, Françoise; Dardevet, Dominique; Dubray, Claude; Papet, Isabelle

    2012-02-01

    Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (±SEM) age 74 ± 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation.

  14. Metabolic engineering for microbial production of aromatic amino acids and derived compounds.

    PubMed

    Bongaerts, J; Krämer, M; Müller, U; Raeven, L; Wubbolts, M

    2001-10-01

    Metabolic engineering to design and construct microorganisms suitable for the production of aromatic amino acids and derivatives thereof requires control of a complicated network of metabolic reactions that partly act in parallel and frequently are in rapid equilibrium. Engineering the regulatory circuits, the uptake of carbon, the glycolytic pathway, the pentose phosphate pathway, and the common aromatic amino acid pathway as well as amino acid importers and exporters that have all been targeted to effect higher productivities of these compounds are discussed.

  15. How prevalent is crassulacean acid metabolism among vascular epiphytes?

    PubMed

    Zotz, Gerhard

    2004-01-01

    The occurrence of crassulacean acid metabolism (CAM) in the epiphyte community of a lowland forest of the Atlantic slope of Panama was investigated. I hypothesized that CAM is mostly found in orchids, of which many species are relatively small and/or rare. Thus, the relative proportion of species with CAM should not be a good indicator for the prevalence of this photosynthetic pathway in a community when expressed on an individual or a biomass basis. In 0.4 ha of forest, 103 species of vascular epiphytes with 13,099 individuals were found. As judged from the C isotope ratios and the absence of Kranz anatomy, CAM was detected in 20 species (19.4% of the total), which were members of the families Orchidaceae, Bromeliaceae, and Cactaceae. As predicted, the contribution of CAM epiphytes to the total number of individuals and to total biomass (69.6 kg ha(-1)) was considerably lower (3.6% or 466 individuals and, respectively, 3.0% or 2.1 kg ha(-1)).

  16. Cytochrome P450 arachidonic acid metabolism in bovine corneal epithelium

    SciTech Connect

    Masferrer, J.; Schwartzman, M.L.; Abraham, N.G.; Dunn, M.W.; McGiff, J.C.

    1986-03-01

    The presence of the cytochrom P450 system and its involvement in the metabolism of AA was studied in the corneal epithelium. This tissue contains cytochrome P450 as assessed directly by measurement of the carbon monoxide reduced spectrum (specific activity of 161 pmol/10 mg protein) and indirectly by measuring the activity of aryl hydrocarbon hydroxylase (AHH) - a cytochrome P450-dependent enzyme (11-39 pmol 3-OH benzopyrene/mg protein/10 min). When corneal epithelial microsomes were incubated with /sup 14/C-arachidonic acid, 30-50% of the total radioactivity was converted to two peaks, I and II. Further separation using high performance liquid chromatography has shown that each peak contains two metabolites, A,B and C,D. Metabolite formation was dependent on the addition of NADPH (1 mM) and inhibited by carbon monoxide and SKF-525A (100 ..mu..M) suggesting a cytochrome P450-dependent mechanism. Compound C (5-10 ..mu..M) inhibited the activity of corneal epithelial Na-K-ATPase by 30-60%, being 100-fold more potent than ouabain. Compound D (10-100 ng) induced a dose dependent relaxation of the rat caudal artery. Compound D also inhibited corneal Na-K-ATPase activity but less potently than compound C. These compounds may be important to transport processes of ocular epithelia and participate in the control of the ocular circulation and aqueous humor dynamics.

  17. Tissue-specific Short Chain Fatty Acid Metabolism and Slow Metabolic Recovery after Ischemia from Hyperpolarized NMR in Vivo*

    PubMed Central

    Jensen, Pernille R.; Peitersen, Torben; Karlsson, Magnus; in 't Zandt, René; Gisselsson, Anna; Hansson, Georg; Meier, Sebastian; Lerche, Mathilde H.

    2009-01-01

    Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into acyl-carnitine pools shows the efficient buffering of free CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even found in liver, where acetyl-CoA synthetase and acetyl-carnitine transferase activities have been assumed sequestered in different compartments. In vivo assays of altered acetate metabolism were applied to characterize pathological changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired mitochondrial metabolism and slow restoration of free CoA are corroborated by assays employing fumarate to show persistently reduced tricarboxylic acid (TCA) cycle activity upon ischemia. In the same animal model, anaerobic metabolism of pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics. PMID:19861411

  18. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

    PubMed Central

    Munger, Joshua; Bennett, Bryson D; Parikh, Anuraag; Feng, Xiao-Jiang; McArdle, Jessica; Rabitz, Herschel A; Shenk, Thomas; Rabinowitz, Joshua D

    2010-01-01

    Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication. We developed a flux measurement approach based on liquid chromatography–tandem mass spectrometry to quantify changes in metabolic activity induced by human cytomegalovirus (HCMV). This approach reliably elucidated fluxes in cultured mammalian cells by monitoring metabolome labeling kinetics after feeding cells 13C-labeled forms of glucose and glutamine. Infection with HCMV markedly upregulated flux through much of the central carbon metabolism, including glycolysis. Particularly notable increases occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis suppressed the replication of both HCMV and influenza A, another enveloped virus. These results show that fatty acid synthesis is essential for the replication of two divergent enveloped viruses and that systems-level metabolic flux profiling can identify metabolic targets for antiviral therapy. PMID:18820684

  19. Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

    PubMed

    Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

    2015-07-01

    It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

  20. Disorders of Carbohydrate Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Carbohydrates are sugars. ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism NOTE: This is ...

  1. Difference in amounts between titratable acid and total carboxylic acids produced by oral streptococci during sugar metabolism.

    PubMed

    Iwami, Y; Hata, S; Takahashi, N; Yamada, T

    1989-01-01

    The acid produced by the resting cells of Streptococcus mutants NCTC 10449 and HS 6 and S. sanguis ATCC 10556 during sugar metabolism was estimated with a pH-stat and a carboxylic acid analyzer. Lactic, formic, acetic, pyruvic, and carbonic acids were detected in the reaction mixtures, but propionic, citric, succinic, iso-butyric, butyric, iso-valeric, and valeric acids were not detected. The amount of titratable acid estimated by alkaline titration with the pH-stat was larger than the amount of total carboxylic acids estimated with the carboxylic acid analyzer. The difference in quantity between the titratable and the total carboxylic acids increased significantly with an increase in the period of incubation with sugar. Moreover, the value of the alkaline titration of standard lactic, formic, acetic, and pyruvic acids was equal to the amount analyzed with the carboxylic acid analyzer. The results indicated that these two streptococci produced not only these carboxylic acids but also other acid(s), possibly non-carboxylic acid(s), during their sugar metabolism.

  2. L-Lactic acid production from glycerol coupled with acetic acid metabolism by Enterococcus faecalis without carbon loss.

    PubMed

    Murakami, Nao; Oba, Mana; Iwamoto, Mariko; Tashiro, Yukihiro; Noguchi, Takuya; Bonkohara, Kaori; Abdel-Rahman, Mohamed Ali; Zendo, Takeshi; Shimoda, Mitsuya; Sakai, Kenji; Sonomoto, Kenji

    2016-01-01

    Glycerol is a by-product in the biodiesel production process and considered as one of the prospective carbon sources for microbial fermentation including lactic acid fermentation, which has received considerable interest due to its potential application. Enterococcus faecalis isolated in our laboratory produced optically pure L-lactic acid from glycerol in the presence of acetic acid. Gas chromatography-mass spectrometry analysis using [1, 2-(13)C2] acetic acid proved that the E. faecalis strain QU 11 was capable of converting acetic acid to ethanol during lactic acid fermentation of glycerol. This indicated that strain QU 11 restored the redox balance by oxidizing excess NADH though acetic acid metabolism, during ethanol production, which resulted in lactic acid production from glycerol. The effects of pH control and substrate concentration on lactic acid fermentation were also investigated. Glycerol and acetic acid concentrations of 30 g/L and 10 g/L, respectively, were expected to be appropriate for lactic acid fermentation of glycerol by strain QU 11 at a pH of 6.5. Furthermore, fed-batch fermentation with 30 g/L glycerol and 10 g/L acetic acid wholly exhibited the best performance including lactic acid production (55.3 g/L), lactic acid yield (0.991 mol-lactic acid/mol-glycerol), total yield [1.08 mol-(lactic acid and ethanol)]/mol-(glycerol and acetic acid)], and total carbon yield [1.06 C-mol-(lactic acid and ethanol)/C-mol-(glycerol and acetic acid)] of lactic acid and ethanol. In summary, the strain QU 11 successfully produced lactic acid from glycerol with acetic acid metabolism, and an efficient fermentation system was established without carbon loss.

  3. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    PubMed Central

    Wiklund, Petri; Zhang, Xiaobo; Pekkala, Satu; Autio, Reija; Kong, Lingjia; Yang, Yifan; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue. PMID:27080554

  4. Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism

    PubMed Central

    Correia, Jorge C.; Massart, Julie; de Boer, Jan Freark; Porsmyr-Palmertz, Margareta; Martínez-Redondo, Vicente; Agudelo, Leandro Z.; Sinha, Indranil; Meierhofer, David; Ribeiro, Vera; Björnholm, Marie; Sauer, Sascha; Dahlman-Wright, Karin; Zierath, Juleen R.; Groen, Albert K.; Ruas, Jorge L.

    2015-01-01

    Objective Farnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known. Methods We expressed each FXR variant in primary hepatocytes and evaluated global gene expression, lipid profile, and metabolic fluxes. Gene delivery of FXR variants to Fxr−/− mouse liver was performed to evaluate their role in vivo. The effects of fasting and physical exercise on hepatic Fxr splicing were determined. Results We show that FXR splice isoforms regulate largely different gene sets and have specific effects on hepatic metabolism. FXRα2 (but not α1) activates a broad transcriptional program in hepatocytes conducive to lipolysis, fatty acid oxidation, and ketogenesis. Consequently, FXRα2 decreases cellular lipid accumulation and improves cellular insulin signaling to AKT. FXRα2 expression in Fxr−/− mouse liver activates a similar gene program and robustly decreases hepatic triglyceride levels. On the other hand, FXRα1 reduces hepatic triglyceride content to a lesser extent and does so through regulation of lipogenic gene expression. Bioenergetic cues, such as fasting and exercise, dynamically regulate Fxr splicing in mouse liver to increase Fxrα2 expression. Conclusions Our results show that the main FXR variants in human liver (α1 and α2) reduce hepatic lipid accumulation through distinct mechanisms and to different degrees. Taking this novel mechanism into account could greatly improve the pharmacological targeting and therapeutic efficacy of FXR agonists. PMID:26909306

  5. Nickel Deficiency Disrupts Metabolism of Ureides, Amino Acids, and Organic Acids of Young Pecan Foliage[OA

    PubMed Central

    Bai, Cheng; Reilly, Charles C.; Wood, Bruce W.

    2006-01-01

    The existence of nickel (Ni) deficiency is becoming increasingly apparent in crops, especially for ureide-transporting woody perennials, but its physiological role is poorly understood. We evaluated the concentrations of ureides, amino acids, and organic acids in photosynthetic foliar tissue from Ni-sufficient (Ni-S) versus Ni-deficient (Ni-D) pecan (Carya illinoinensis [Wangenh.] K. Koch). Foliage of Ni-D pecan seedlings exhibited metabolic disruption of nitrogen metabolism via ureide catabolism, amino acid metabolism, and ornithine cycle intermediates. Disruption of ureide catabolism in Ni-D foliage resulted in accumulation of xanthine, allantoic acid, ureidoglycolate, and citrulline, but total ureides, urea concentration, and urease activity were reduced. Disruption of amino acid metabolism in Ni-D foliage resulted in accumulation of glycine, valine, isoleucine, tyrosine, tryptophan, arginine, and total free amino acids, and lower concentrations of histidine and glutamic acid. Ni deficiency also disrupted the citric acid cycle, the second stage of respiration, where Ni-D foliage contained very low levels of citrate compared to Ni-S foliage. Disruption of carbon metabolism was also via accumulation of lactic and oxalic acids. The results indicate that mouse-ear, a key morphological symptom, is likely linked to the toxic accumulation of oxalic and lactic acids in the rapidly growing tips and margins of leaflets. Our results support the role of Ni as an essential plant nutrient element. The magnitude of metabolic disruption exhibited in Ni-D pecan is evidence of the existence of unidentified physiological roles for Ni in pecan. PMID:16415214

  6. Perfluorononanoic acid disturbed the metabolism of lipid in the liver of streptozotocin-induced diabetic rats.

    PubMed

    Fang, Xuemei; Gao, Guizhen; Zhang, Xingtao; Wang, Haichao

    2015-01-01

    Most studies on the liver toxicity of perfluorinated compounds (PFCs) are focused on healthy individuals, whereas the effects of PFCs on individuals with diabetes mellitus have not been fully characterized. This study aimed to investigate the acute exposure of perfluorononanoic acid (PFNA) on the metabolism of lipid in the liver of streptozotocin-induced diabetic rats. Male diabetic rats were orally dosed by gavage for 7 days with 0, 0.2, 1 and 5 mg/kg/day PFNA. The contents of lipid, the activities of enzyme, the expressions of protein in the liver and the serum parameters were detected. The results indicate that dose-dependent accumulation of triglyceride and total cholesterol occurred in the livers of diabetic rats after PFNA treatment. PFNA increased the activities of lipid synthetase, fatty acid synthease, glucose-6-phosphate dehydrogenase and decreased the activity of lipolytic enzyme, hepatic lipase, in the liver of diabetic rats. The changes of the isocitrate dehydrogenase, malicenzyme and lipoprotein lipase were not obvious. The expressions of protein related to lipid homeostasis, liver X receptor α and apolipoprotein E, were decreased after PFNA administration. Exposure to PFNA also increased the activity of serum alanine aminotransferase in diabetic rats. In conclusion, this study discloses that exposure to PFNA impacts on enzymes and proteins related to liver lipid metabolism and lead to obvious accumulation of lipid in the liver of diabetic rats, which may be responsible for hepatotoxicity of this compound in individuals with diabetes mellitus.

  7. Conjugated linoleic acids influence fatty acid metabolism in ovine ruminal epithelial cells.

    PubMed

    Masur, F; Benesch, F; Pfannkuche, H; Fuhrmann, H; Gäbel, G

    2016-04-01

    Conjugated linoleic acids (CLA), particularly cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12), are used as feed additives to adapt to constantly increasing demands on the performance of lactating cows. Under these feeding conditions, the rumen wall, and the rumen epithelial cells (REC) in particular, are directly exposed to high amounts of CLA. This study determined the effect of CLA on the fatty acid (FA) metabolism of REC and expression of genes known to be modulated by FA. Cultured REC were incubated with c9t11, t10c12, and the structurally similar FA linoleic acid (LA), oleic acid (OA), and trans-vaccenic acid (TVA) for 48 h at a concentration of 100 µM. Cellular FA levels were determined by gas chromatography. Messenger RNA expression levels of stearoyl-CoA desaturase (SCD) and monocarboxylate transporter (MCT) 1 and 4 were quantified by reverse transcription-quantitative PCR. Fatty acid evaluation revealed significant effects of CLA, LA, OA, and TVA on the amount of FA metabolites of β-oxidation and elongation and of metabolites related to desaturation by SCD. The observed changes in FA content point (among others) to the ability of REC to synthesize c9t11 from TVA endogenously. The mRNA expression levels of SCD identified a decrease after CLA, LA, OA, or TVA treatment. In line with the changes in mRNA expression, we found reduced amounts of C16:1n-7 cis-9 and C18:1n-9 cis-9, the main products of SCD. The expression of MCT1 mRNA increased after c9t11 and t10c12 treatment, and CLA c9t11 induced an upregulation of MCT4. Application of peroxisome proliferator-activated receptor (PPAR) α antagonist suggested that activation of PPARα is involved in the changes of MCT1, MCT4, and SCD mRNA expression induced by c9t11. Participation of PPARγ in the changes of MCT1 and SCD mRNA expression was shown by the application of the respective antagonist. The study demonstrates that exposure to CLA affects both FA metabolism and regulatory pathways within REC.

  8. Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome

    PubMed Central

    Bhansali, Shobhit; Shafiq, Nusrat; Pandhi, Promila; Singh, Amrit Pal; Singh, Inderjeet; Singh, Pawan Kumar; Sharma, Sadhna; Malhotra, Samir

    2013-01-01

    Background & objectives: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. Methods: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. Results: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. Interpretation & conclusions: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action. PMID:23852298

  9. Involvement of carnitine acyltransferases in peroxisomal fatty acid metabolism by the yeast Pichia guilliermondii.

    PubMed Central

    Pagot, Y; Belin, J M

    1996-01-01

    This article provides information about peroxisomal fatty acid metabolism in the yeast Pichia guilliermondii. The existence of inducible mitochondrial carnitine palmitoyltransferase and peroxisomal carnitine octanoyl-transferase activities was demonstrated after culture of this yeast in a medium containing methyl oleate. The subcellular sites and induction patterns were studied. The inhibition of carnitine octanoyl- and palmitoyl-transferases by chlorpromazine to a large extent prevented the otherwise observed metabolism-dependent inactivation of thiolase by 2-bromofatty acids in vivo. We concluded that the metabolism of long- and medium-chain fatty acids in the peroxisome of this yeast involved carnitine intermediates. PMID:8837442

  10. Variation in the Carbon Isotope Composition of a Plant with Crassulacean Acid Metabolism

    PubMed Central

    Lerman, J. C.; Deleens, Eliane; Nato, Aimé; Moyse, Alexis

    1974-01-01

    The content of 13C varies in plants with Crassulacean acid metabolism. Differences up to 3.5‰ in the 13C/12C ratios were observed between leaves of different age in the same plant of Bryophyllum daigremontianum. Soluble and insoluble carbon in the same leaf differed up to 8‰, the largest difference occurring in the leaves with the highest Crassulacean acid metabolism activity. Models to account for the isotope discrimination by C3, C4, and Crassulacean acid metabolism plants are proposed. PMID:16658746

  11. Role of bile acids in the regulation of the metabolic pathways

    PubMed Central

    Taoka, Hiroki; Yokoyama, Yoko; Morimoto, Kohkichi; Kitamura, Naho; Tanigaki, Tatsuya; Takashina, Yoko; Tsubota, Kazuo; Watanabe, Mitsuhiro

    2016-01-01

    Recent studies have revealed that bile acids (BAs) are not only facilitators of dietary lipid absorption but also important signaling molecules exerting multiple physiological functions. Some major signaling pathways involving the nuclear BAs receptor farnesoid X receptor and the G protein-coupled BAs receptor TGR5/M-BAR have been identified to be the targets of BAs. BAs regulate their own homeostasis via signaling pathways. BAs also affect diverse metabolic pathways including glucose metabolism, lipid metabolism and energy expenditure. This paper suggests the mechanism of controlling metabolism via BA signaling and demonstrates that BA signaling is an attractive therapeutic target of the metabolic syndrome. PMID:27433295

  12. Metabolism of xenobiotic carboxylic acids: focus on coenzyme A conjugation, reactivity, and interference with lipid metabolism.

    PubMed

    Darnell, Malin; Weidolf, Lars

    2013-08-19

    While xenobiotic carboxylic acids (XCAs) have been studied extensively with respect to their enzymatic conversion to potentially reactive acyl glucuronides with implications to drug induced hepatotoxicity, the formation of xenobiotic-S-acyl-CoA thioesters (xenobiotic-CoAs) have been much less studied in spite of data indicating that such conjugates may be equally or more reactive than the corresponding acyl glucuronides. This review addresses enzymes and cell organelles involved in the formation of xenobiotic-CoAs, the reactivity of such conjugates toward biological macromolecules, and in vitro and in vivo methodology to assess consequences of such reactivity. Further, the propensity of xenobiotic-CoAs to interfere with endogenous lipid metabolism, e.g., inhibition of β-oxidation or depletion of the CoA or carnitine pools, adds to the complexity of the potential contribution of XCAs to hepatotoxicity by a number of mechanisms in addition to those in common with the corresponding acyl glucuronides. On the basis of our review of the literature on xenobiotic-CoA conjugates, there appear to be a number of gaps in our understanding of the bioactivation of XCA both with respect to the mechanisms involved and the experimental approaches to distinguish between the role of acyl glucuronides and xenobiotic-CoA conjugates. These aspects are focused upon and described in detail in this review.

  13. Crassulacean acid metabolism-cycling in Euphorbia milii

    PubMed Central

    Herrera, Ana

    2013-01-01

    Crassulacean acid metabolism (CAM) occurs in many Euphorbiaceae, particularly Euphorbia, a genus with C3 and C4 species as well. With the aim of contributing to our knowledge of the evolution of CAM in this genus, this study examined the possible occurrence of CAM in Euphorbia milii, a species with leaf succulence and drought tolerance suggestive of this carbon fixation pathway. Leaf anatomy consisted of a palisade parenchyma, a spongy parenchyma and a bundle sheath with chloroplasts, which indicates the possible functioning of C2 photosynthesis. No evidence of nocturnal CO2 fixation was found in plants of E. milii either watered or under drought; watered plants had a low nocturnal respiration rate (R). After 12 days without watering, the photosynthetic rate (PN) decreased 85 % and nocturnal R was nearly zero. Nocturnal H+ accumulation (ΔH+) in watered plants was 18 ± 2 (corresponding to malate) and 18 ± 4 (citrate) μmol H+ (g fresh mass)−1. Respiratory CO2 recycling through acid synthesis contributed to a night-time water saving of 2 and 86 % in watered plants and plants under drought, respectively. Carbon isotopic composition (δ13C) was −25.2 ± 0.7 ‰ in leaves and −24.7 ± 0.1 ‰ in stems. Evidence was found for the operation of weak CAM in E. milii, with statistically significant ΔH+, no nocturnal CO2 uptake and values of δ13C intermediate between C3 and constitutive CAM plants; ΔH+ was apparently attributable to both malate and citrate. The results suggest that daily malate accumulation results from recycling of part of the nocturnal respiratory CO2, which helps explain the occurrence of an intermediate value of leaf δ13C. Euphorbia milii can be considered as a CAM-cycling species. The significance of the operation of CAM-cycling in E. milii lies in water conservation, rather than carbon acquisition. The possible occurrence of C2 photosynthesis merits research. PMID:23596548

  14. An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid.

    PubMed

    Zhao, Chunyan; Sun, Runbin; Cao, Bei; Gu, Shenghua; Zhao, Jieyu; Liu, Linsheng; Wang, Xinwen; Zha, Weibin; Yu, Xiaoyi; Xiao, Wenjing; Mao, Yong; Ge, Chun; Ju, Jiaqi; Aa, Lixiang; Fei, Fei; Ding, Yi; Aa, Jiye; Wang, Guangji

    2014-06-01

    For orally administered drugs, the metabolism of a drug by the gut flora plays an important role in the bioavailability, activation and disposition of the drug in vivo. However, no in vitro system is currently available to evaluate the metabolism of a drug by the gut flora before the drug is absorbed into the body. This paper presents an in vitro metabolic system in an anaerobic environment that could be used to evaluate the metabolism of an endogenous compound, cholic acid, and a xenobiotic compound, ginsenoside Rg3. We showed that the proliferation of the anaerobic bacteria of the gut content of hamsters produced a similar composition of gut flora in a culture medium for yeast to that in vivo. Incubation of ginsenoside Rg3 and cholic acid in the anaerobic in vitro system efficiently produced the metabolites Rh2 and deoxycholic acid, respectively, similar to those seen in the gut content in vivo. In comparison with in vivo analysis, this anaerobic in vitro metabolic system is convenient, reproducible, economic and animal saving, and can easily be applied to assess the transformation and disposition of a drug before it enters into the circulatory system.

  15. (13)C Metabolic Flux Analysis for Systematic Metabolic Engineering of S. cerevisiae for Overproduction of Fatty Acids.

    PubMed

    Ghosh, Amit; Ando, David; Gin, Jennifer; Runguphan, Weerawat; Denby, Charles; Wang, George; Baidoo, Edward E K; Shymansky, Chris; Keasling, Jay D; García Martín, Héctor

    2016-01-01

    Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here, we used flux-based modeling approaches to improve yields of fatty acids in Saccharomyces cerevisiae. We combined (13)C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Yarrowia lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for downregulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg/L of free fatty acids. With the addition of ATP citrate lyase and downregulation of malate synthase, the engineered strain produced 26% more free fatty acids. Further increases in free fatty acid production of 33% were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by ~70%.

  16. 13C Metabolic Flux Analysis for Systematic Metabolic Engineering of S. cerevisiae for Overproduction of Fatty Acids

    PubMed Central

    Ghosh, Amit; Ando, David; Gin, Jennifer; Runguphan, Weerawat; Denby, Charles; Wang, George; Baidoo, Edward E. K.; Shymansky, Chris; Keasling, Jay D.; García Martín, Héctor

    2016-01-01

    Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here, we used flux-based modeling approaches to improve yields of fatty acids in Saccharomyces cerevisiae. We combined 13C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Yarrowia lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for downregulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg/L of free fatty acids. With the addition of ATP citrate lyase and downregulation of malate synthase, the engineered strain produced 26% more free fatty acids. Further increases in free fatty acid production of 33% were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by ~70%. PMID:27761435

  17. Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids.

    PubMed

    Beld, Joris; Abbriano, Raffaela; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D

    2016-04-01

    In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short

  18. Effects of Iron Overload on Ascorbic Acid Metabolism*

    PubMed Central

    Wapnick, A. A.; Lynch, S. R.; Krawitz, P.; Seftel, H. C.; Charlton, R. W.; Bothwell, T. H.

    1968-01-01

    Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid. PMID:5673960

  19. Effects of iron overload on ascorbic acid metabolism.

    PubMed

    Wapnick, A A; Lynch, S R; Krawitz, P; Seftel, H C; Charlton, R W; Bothwell, T H

    1968-09-21

    Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid.

  20. PPARα Association With Sirt1 Suppresses Cardiac Fatty Acid Metabolism in the Failing Heart

    PubMed Central

    Oka, Shin-ichi; Zhai, Peiyong; Yamamoto, Takanobu; Ikeda, Yoshiyuki; Byun, Jaemin; Hsu, Chiao-Po; Sadoshima, Junichi

    2015-01-01

    Background Heart failure (HF) is accompanied by changes in cardiac metabolism characterized by reduced fatty acid (FA) utilization. However, the underlying mechanism and its causative involvement in the progression of HF are poorly understood. The peroxisome proliferator activated receptor-α (PPARα)/retinoid X receptor (RXR) heterodimer promotes transcription of genes involved in FA metabolism through binding to the PPAR response element, called direct repeat 1 (DR1). Silent information regulator 1 (Sirt1) is a histone deacetylase which interacts with PPARα. Methods and Results To investigate the role of PPARα in the impaired FA utilization observed during HF, genetically altered mice were subjected to pressure overload (PO). The DNA binding of PPARα, RXRα and Sirt1 to DR1 was evaluated with oligonucleotide pull-down and chromatin immunoprecipitation assays. Although the binding of PPARα to DR1 was enhanced in response to PO, that of RXRα was attenuated. Sirt1 competes with RXRα to dimerize with PPARα, thereby suppressing FA utilization in the failing heart. DR1 sequence analysis indicated that the typical DR1 sequence favors PPARα/RXRα heterodimerization, whereas the switch from RXRα to Sirt1 takes place on degenerate DR1s. Sirt1 bound to PPARα through a region homologous to the PPARα binding domain in RXRα. A short peptide corresponding to the RXRα domain not only inhibited the interaction between PPARα and Sirt1 but also improved FA metabolism and ameliorated cardiac dysfunction. Conclusions A change in the heterodimeric partner of PPARα from RXRα to Sirt1 is responsible for the impaired FA metabolism and cardiac dysfunction in the failing heart. PMID:26443578

  1. Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites.

    PubMed

    Cooper, George; Reed, Chris; Nguyen, Dang; Carter, Malika; Wang, Yi

    2011-08-23

    Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a "one pot" suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using (13)C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems.

  2. Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism.

    PubMed

    Evans, Simon J; Ringrose, Rachel N; Harrington, Gloria J; Mancuso, Peter; Burant, Charles F; McInnis, Melvin G

    2014-10-01

    Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder.

  3. How to Do It. Plant Eco-Physiology: Experiments on Crassulacean Acid Metabolism, Using Minimal Equipment.

    ERIC Educational Resources Information Center

    Friend, Douglas J. C.

    1990-01-01

    Features of Crassulacean Acid Metabolism plants are presented. Investigations of a complex eco-physiological plant adaptation to the problems of growth in an arid environment are discussed. Materials and procedures for these investigations are described. (CW)

  4. Study of stationary phase metabolism via isotopomer analysis of amino acids from an isolated protein.

    PubMed

    Shaikh, Afshan S; Tang, Yinjie J; Mukhopadhyay, Aindrila; Martín, Héctor García; Gin, Jennifer; Benke, Peter I; Keasling, Jay D

    2010-01-01

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully (13)C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  5. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    SciTech Connect

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  6. BIOCONCENTRATION AND METABOLISM OF ALL-TRANS RETINOIC ACID BY RANA SYLVATICA AND RANA CLAMITANS TADPOLES

    EPA Science Inventory

    Retinoids, which are Vitamin A derivatives, are important signaling molecules that regulate processes critical for development in all vertebrates. The objective of our study was to examine uptake and metabolism of all-trans retinoic acid...

  7. The use of dilute hydrochloric acid and cimetidine to reverse severe metabolic alkalosis.

    PubMed

    Rowlands, B J; Tindall, S F; Elliott, D J

    1978-02-01

    Two cases of severe metabolic alkalosis associated with gastric hypersecretion were successfully treated with dilute hydrochloric acid and a histamine H2-receptor antagonist given by intravenous infusion. This combined therapy with electrolyte replacement and suppression of gastric secretion is valuable in the control of this serious metabolic abnormality when conventional treatment is unsuccessful or contraindicated.

  8. Identification and transcriptional profiling of Pseudomonas putida genes involved in furoic acid metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Furfural (2-furaldehyde) is a furan formed by dehydration of pentose sugars. Pseudomonas putida Fu1 metabolizes furfural through a pathway involving conversion to 2-oxoglutarate, via 2-furoic acid and Coenzyme A intermediates. To identify genes involved in furan metabolism, two P. putida transposo...

  9. Systems metabolic engineering design: Fatty acid production as an emerging case study

    PubMed Central

    Tee, Ting Wei; Chowdhury, Anupam; Maranas, Costas D; Shanks, Jacqueline V

    2014-01-01

    Increasing demand for petroleum has stimulated industry to develop sustainable production of chemicals and biofuels using microbial cell factories. Fatty acids of chain lengths from C6 to C16 are propitious intermediates for the catalytic synthesis of industrial chemicals and diesel-like biofuels. The abundance of genetic information available for Escherichia coli and specifically, fatty acid metabolism in E. coli, supports this bacterium as a promising host for engineering a biocatalyst for the microbial production of fatty acids. Recent successes rooted in different features of systems metabolic engineering in the strain design of high-yielding medium chain fatty acid producing E. coli strains provide an emerging case study of design methods for effective strain design. Classical metabolic engineering and synthetic biology approaches enabled different and distinct design paths towards a high-yielding strain. Here we highlight a rational strain design process in systems biology, an integrated computational and experimental approach for carboxylic acid production, as an alternative method. Additional challenges inherent in achieving an optimal strain for commercialization of medium chain-length fatty acids will likely require a collection of strategies from systems metabolic engineering. Not only will the continued advancement in systems metabolic engineering result in these highly productive strains more quickly, this knowledge will extend more rapidly the carboxylic acid platform to the microbial production of carboxylic acids with alternate chain-lengths and functionalities. PMID:24481660

  10. [Metabolic pathway and metabolites of total diterpene acid isolated from Pseudolarix kaempferi].

    PubMed

    Liu, Peng; Guo, Hong-Zhu; Sun, Jiang-Hao; Xu, Man; Guo, Hui; Sun, Shi-Feng; Guo, De-An

    2014-08-01

    The preliminary metabolic profile of total diterpene acid (TDA) isolated from Pseudolarix kaempferi was investigated by using in vivo and in vitro tests. Pseudolaric acid C2 (PC2) was identified as the predominant metabolite in plasma, urine, bile and feces after both oral and intravenous administrations to rats using HPLC-UV and HPLC-ESI/MS(n), and demethoxydeacetoxypseudolaric acid B (DDPB), a metabolite proposed to be the glucoside of PC2 (PC2G), as well as pseudolaric acid C (PC), pseudolaric acid A (PA), pseudolaric acid A O-beta-D glucopyranoside (PAG), pseudolaric acid B O-beta-D glucopyranoside (PBG) and deacetylpseudolaric acid A (DPA) originated from TDA could also be detected. It was demonstrated by tests that the metabolism of TDA is independent of intestinal microflora, and neither of pepsin and trypsin is in charge of metabolism of TDA, TDA is also stable in both pH environments of gastric tract and intestinal tract. The metabolites of TDA in whole blood in vitro incubation were found to be PC2, DDPB and PC2G, which demonstrated that the metabolic reaction of TDA in vivo is mainly occurred in blood and contributed to be the hydrolysis of plasma esterase to ester bond, as well as the glucosylation reaction. These results clarified the metabolic pathway of TDA for the first time, which is of great significance to the in vivo active form and acting mechanism research of P. kaempferi.

  11. Genome-wide association studies for fatty acid metabolic traits in five divergent pig populations

    PubMed Central

    Zhang, Wanchang; Bin Yang; Zhang, Junjie; Cui, Leilei; Ma, Junwu; Chen, Congying; Ai, Huashui; Xiao, Shijun; Ren, Jun; Huang, Lusheng

    2016-01-01

    Fatty acid composition profiles are important indicators of meat quality and tasting flavor. Metabolic indices of fatty acids are more authentic to reflect meat nutrition and public acceptance. To investigate the genetic mechanism of fatty acid metabolic indices in pork, we conducted genome-wide association studies (GWAS) for 33 fatty acid metabolic traits in five pig populations. We identified a total of 865 single nucleotide polymorphisms (SNPs), corresponding to 11 genome-wide significant loci on nine chromosomes and 12 suggestive loci on nine chromosomes. Our findings not only confirmed seven previously reported QTL with stronger association strength, but also revealed four novel population-specific loci, showing that investigations on intermediate phenotypes like the metabolic traits of fatty acids can increase the statistical power of GWAS for end-point phenotypes. We proposed a list of candidate genes at the identified loci, including three novel genes (FADS2, SREBF1 and PLA2G7). Further, we constructed the functional networks involving these candidate genes and deduced the potential fatty acid metabolic pathway. These findings advance our understanding of the genetic basis of fatty acid composition in pigs. The results from European hybrid commercial pigs can be immediately transited into breeding practice for beneficial fatty acid composition. PMID:27097669

  12. Metabolic engineering of Pichia pastoris to produce ricinoleic acid, a hydroxy fatty acid of industrial importance[S

    PubMed Central

    Meesapyodsuk, Dauenpen; Chen, Yan; Ng, Siew Hon; Chen, Jianan; Qiu, Xiao

    2015-01-01

    Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fatty acid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a “push” (synthesis) and “pull” (assembly) strategy. CpFAH, a fatty acid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fatty acid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fatty acid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses. PMID:26323290

  13. Conclusions

    NASA Astrophysics Data System (ADS)

    Ahonen, Pasi; Alahuhta, Petteri; Daskala, Barbara; Delaitre, Sabine; Hert, Paul De; Lindner, Ralf; Maghiros, Ioannis; Moscibroda, Anna; Schreurs, Wim; Verlinden, Michiel

    Some say that an increase in security does not necessarily mean a further encroachment on privacy - indeed, security is necessary to protect personal data and our privacy. Networks must be secure, our personal devices, reliable, dependable and trustworthy. But security is a multifaceted term, with many dimensions. We are of the view that an increase in security most likely will encroach upon our privacy in an ambient intelligence world. Surveillance cameras will continue to proliferate. We assume that, whatever the law is, whatever privacy protections government and business say they honour, our telecommunications, e-mails and Internet usage will be monitored to an increasing degree. The same will be true of our interfaces with the world of ambient intelligence.

  14. Conclusion

    NASA Astrophysics Data System (ADS)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    It is often held that things should always be made simple, which presumes that either that they can always be made simple or that all the jetisoned logic doesn't matter anyway. Alledgedly, anything should be explainable so that anyone can understand it. Don't get bogged down in dreary details. It should be effortless for the reader: low-dimensional systems exhibit complex behaviour while high-dimensional systems exhibit simple behaviour (to return to our prolegomonal opening), competition is a universal solution, demand must increase as price falls, and everything under the sun neatly fits a power law. Or so the story goes...

  15. Conclusions

    NASA Astrophysics Data System (ADS)

    Binder, P.-M.; Smith, K.

    If you made it to this point, this is what we have tried to offer you: a view of language like no other book has provided before. It is quite possible that this is one of very few books you have read on the subject; it could even be your first. Chances are that those you have read were written for a general audience. Some of them are very good, but they usually try to push a particular viewpoint of their author. Or you may have followed an introductory linguistics course at the university level. Such courses, and their textbooks, focus on technical aspects of the subject: the details of theories of phonology, syntax, semantics and so on. Knowledge of all of these areas is absolutely necessary for a deep understanding of the subject. But both single-author general books and technical textbooks have the same shortcoming: they do not give the reader a broad and complete account of how language works.

  16. Conclusion

    NASA Technical Reports Server (NTRS)

    Arnold, Steven M.; Wong, Terry T.

    2011-01-01

    This compilation of papers in this book represents approximately half of the works discussed at the MS&T 2010 symposium entitled Tools, Models, Databases, and Simulation Tools Developed and Needed to Realize the Vision of Integrated Computational Materials Engineering at Materials Science & Technology wherein five sessions comprised of 33 presentations was organized. The goal of the symposium was two fold To provide a forum in which current state-of-the-art methods for ICME (e.g., information informatics, experimentation, and modeling) could be openly discussed and critiqued by not only materials scientist but also structural engineers/researchers, component designers, industrial leaders and government program managers. To leave the symposium and in particular the panel discussion with a clear idea of the gaps and barriers (both technical, cultural and economical) that must be addressed in order for ICME to fully succeed. The organizers felt that these goals were met, as particularly evident by the standing room only attendance during a lively panel discussion session at the end of the Symposium. However it is the firm belief of the editors of this book that this symposium was merely a start in the right direction, and that subsequent conferences/symposium (e.g., First World Congress on Integrated Computational Materials Engineering to be held July 10-14, 2011 at Seven Springs Mountain Resort in Pennsylvania) must work hard to ensure that a truly diverse, multidisciplinary, community of researchers and practitioners are present and have ample opportunity for interaction. This will ensure that a proper balance between push and pull disciplines and technologies is maintained so that this emerging focus area, Integrated Computational Materials Engineering (ICME), has the greatest potential for success and impact on "system-level" payoffs. Similarly, a pro-active approach is required to reform historical modes of operation in industry, government and the academic sectors so as to facilitate multidisciplinary collaboration and to clearly articulate the vision and scope of ICME.

  17. Central metabolic responses to the overproduction of fatty acids in Escherichia coli based on 13C-metabolic flux analysis.

    PubMed

    He, Lian; Xiao, Yi; Gebreselassie, Nikodimos; Zhang, Fuzhong; Antoniewiez, Maciek R; Tang, Yinjie J; Peng, Lifeng

    2014-03-01

    We engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull-push-block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions. Metabolic fluxes were determined for the engineered E. coli and its control strain using tracer ([1,2-13C]glucose) experiments and 13C-metabolic flux analysis. Cofactor (NADPH) and energy (ATP) balances were also investigated for both strains based on estimated fluxes. Compared to the control strain, fatty acid overproduction led to significant metabolic responses in the central metabolism: (1) Acetic acid secretion flux decreased 10-fold; (2) Pentose phosphate pathway and Entner–Doudoroff pathway fluxes increased 1.5- and 2.0-fold, respectively; (3) Biomass synthesis flux was reduced 1.9-fold; (4) Anaplerotic phosphoenolpyruvate carboxylation flux decreased 1.7-fold; (5) Transhydrogenation flux converting NADH to NADPH increased by 1.7-fold. Real-time quantitative RT-PCR analysis revealed the engineered strain increased the transcription levels of pntA (encoding the membrane-bound transhydrogenase) by 2.1-fold and udhA (encoding the soluble transhydrogenase) by 1.4-fold, which is in agreement with the increased transhydrogenation flux. Cofactor and energy balances analyses showed that the fatty acid overproducing E. coli consumed significantly higher cellular maintenance energy than the control strain. We discussed the strategies to future strain development and process improvements for fatty acid production in E. coli.

  18. Metabolic programming of long-term outcomes due to fatty acid nutrition in early life.

    PubMed

    Innis, Sheila M

    2011-04-01

    Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω-6 and decrease in ω-3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω-6 and ω-3 fatty acids in gestation and lactation, possibly involving both excess ω-6 and inadequate ω-3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω-6 and ω-3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism.

  19. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    PubMed Central

    Xie, Guoxiang; Zhong, Wei; Li, Houkai; Li, Qiong; Qiu, Yunping; Zheng, Xiaojiao; Chen, Huiyuan; Zhao, Xueqing; Zhang, Shucha; Zhou, Zhanxiang; Zeisel, Steven H.; Jia, Wei

    2013-01-01

    Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids in multiple body compartments (liver, gastrointestinal tract, and serum) of rats. Rats were fed a modified Lieber-DeCarli liquid diet with 38% of calories as ethanol (the amount equivalent of 4–5 drinks in humans). While conjugated bile acids predominated in the liver (98.3%), duodenum (97.8%), and ileum (89.7%), unconjugated bile acids comprised the largest proportion of measured bile acids in serum (81.2%), the cecum (97.7%), and the rectum (97.5%). In particular, taurine-conjugated bile acids were significantly decreased in the liver and gastrointestinal tract of ethanol-treated rats, while unconjugated and glycine-conjugated species increased. Ethanol consumption caused increased expression of genes involved in bile acid biosynthesis, efflux transport, and reduced expression of genes regulating bile acid influx transport in the liver. These results provide an improved understanding of the systemic modulations of bile acid metabolism in mammals through the gut-liver axis.—Xie, G., Zhong, W., Li, H., Li, Q., Qiu, Y., Zheng, X., Chen, H., Zhao, X., Zhang, S., Zhou, Z., Zeisel, S. H., Jia, W. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. PMID:23709616

  20. Acute renal failure and metabolic acidosis due to oxalic acid intoxication: a case report.

    PubMed

    Yamamoto, Rie; Morita, Seiji; Aoki, Hiromichi; Nakagawa, Yoshihide; Yamamoto, Isotoshi; Inokuchi, Sadaki

    2011-12-20

    Most of the reports of oxalic acid intoxication are in cases of ethylene glycol intoxication. These symptoms are known to be central nerve system manifestations, cardiopulmonary manifestations and acute renal failure. There have been only a few reports of direct oxalic acid intoxication. However, there have been a few recent reports of oxalic acid intoxication due to the ingestion of star fruit and ascorbic acid. We herein report the case of a patient with acute renal failure and metabolic acidosis caused directly by consumption of oxalic acid. During the initial examination by the physician at our hospital, the patient presented with tachypnea, a precordinal burning sensation, nausea and metabolic acidosis. After admission, the patient developed renal failure and anion gap high metabolic acidosis, but did not develop any CNS or cardio-pulmonary manifestations in the clinical course. The patient benefitted symptomatically from hemodialysis.

  1. Temperature Features of Enzymes Affecting Crassulacean acid Metabolism

    PubMed Central

    Brandon, P. C.

    1967-01-01

    Enzymes involved in malic acid production via a pathway with 2 carboxylation reactions and in malic acid conversion via total oxidation have been demonstrated in mitochondria of Bryophyllum tubiflorum Harv. Activation of the mitochondria by Tween 40 was necessary to reveal part of the enzyme activities. The temperature behavior of the enzymes has been investigated, revealing optimal activity of acid-producing enzymes at 35°. Even at 53° the optimum for acid-converting enzymes was not yet reached. From the simultaneous action of acid-producing and acid-converting enzyme systems the overall result at different temperatures was established. Up to 15° the net result was a malic acid production. Moderate temperatures brought about a decrease in this accumulation, which was partly accompanied by a shift to isocitrate production, while at higher temperatures total oxidation of the acids exceeded the production. PMID:16656606

  2. Fatty acid biosynthesis revisited: structure elucidation and metabolic engineering.

    PubMed

    Beld, Joris; Lee, D John; Burkart, Michael D

    2015-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases' many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field.

  3. Fatty acid biosynthesis revisited: Structure elucidation and metabolic engineering

    SciTech Connect

    Beld, Joris; Lee, D. John; Burkart, Michael D.

    2014-10-20

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases' many intricate structural and regulatory elements. Lastly, in this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field.

  4. Fatty Acid Biosynthesis Revisited: Structure Elucidation and Metabolic Engineering

    PubMed Central

    Beld, Joris; Lee, D. John

    2014-01-01

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases’ many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

  5. Association between fatty acid metabolism in the brain and Alzheimer disease neuropathology and cognitive performance: A nontargeted metabolomic study

    PubMed Central

    An, Yang; Pletnikova, Olga; O’Brien, Richard; Troncoso, John; Legido-Quigley, Cristina; Thambisetty, Madhav

    2017-01-01

    UFAs with neuritic plaque and neurofibrillary tangle burden as well as domain-specific cognitive performance assessed during life. Based on the regional pattern of differences in brain tissue levels of these metabolites, we propose that alterations in UFA metabolism represent both global metabolic perturbations in AD as well as those related to specific features of AD pathology. Within the middle frontal gyrus, decrements in linoleic acid, linolenic acid, and arachidonic acid (control>ASYMAD>AD) and increases in docosahexanoic acid (AD>ASYMAD>control) may represent regionally specific threshold levels of these metabolites beyond which the accumulation of AD pathology triggers the expression of clinical symptoms. The main limitation of this study is the relatively small sample size. There are few cohorts with extensive longitudinal cognitive assessments during life and detailed neuropathological assessments at death, such as the BLSA Conclusions The findings of this study suggest that unsaturated fatty acid metabolism is significantly dysregulated in the brains of patients with varying degrees of Alzheimer pathology. PMID:28323825

  6. The Loss Of Macrophage Fatty Acid Oxidation Does Not Potentiate Systemic Metabolic Dysfunction.

    PubMed

    Gonzalez-Hurtado, Elsie; Lee, Jieun; Choi, Joseph; Selen Alpergin, Ebru S; Collins, Samuel L; Horton, Maureen R; Wolfgang, Michael J

    2017-02-21

    Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase 2 (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation deficient CPT2 Mϕ-KO bone marrow derived macrophages (BMDM) displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although alternatively activated macrophages up-regulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative rather than causative role in systemic metabolic dysfunction.

  7. Metabolism of nonesterified and esterified hydroxycinnamic acids in red wines by Brettanomyces bruxellensis.

    PubMed

    Schopp, Lauren M; Lee, Jungmin; Osborne, James P; Chescheir, Stuart C; Edwards, Charles G

    2013-11-27

    While Brettanomyces can metabolize nonesterified hydroxycinnamic acids found in grape musts/wines (caffeic, p-coumaric, and ferulic acids), it was not known whether this yeast could utilize the corresponding tartaric acid esters (caftaric, p-coutaric, and fertaric acids, respectively). Red wines from Washington and Oregon were inoculated with B. bruxellensis, while hydroxycinnamic acids were monitored by HPLC. Besides consuming p-coumaric and ferulic acids, strains I1a, B1b, and E1 isolated from Washington wines metabolized 40-50% of caffeic acid, a finding in contrast to strains obtained from California wines. Higher molar recoveries of 4-ethylphenol and 4-ethylguaiacol synthesized from p-coumaric and ferulic acids, respectively, were observed in Washington Cabernet Sauvignon and Syrah but not Merlot. This finding suggested that Brettanomyces either (a) utilized vinylphenols formed during processing of some wines or (b) metabolized other unidentified phenolic precursors. None of the strains of Brettanomyces studied metabolized caftaric or p-coutaric acids present in wines from Washington or Oregon.

  8. Metabolism of chicoric acid by rat liver microsomes and bioactivity comparisons of chicoric acid and its metabolites.

    PubMed

    Liu, Qian; Wang, Yutang; Xiao, ChunXia; Wu, Wanqiang; Liu, Xuebo

    2015-06-01

    Chicoric acid has recently become a hot research topic due to its potent bioactivities. However, there are few studies relevant to this acid's pharmacokinetic characteristics and the pharmacological activities of its metabolites. To compare the abilities of chicoric acid and its metabolites in scavenging free radicals and their effects on the viability of 3T3-L1 preadipocytes, an in vitro study of the metabolism of chicoric acid in rat liver microsomes was performed using liquid tandem mass spectrometry (HPLC-MS/MS). The results indicated that caffeic acid and caftaric acid were the hepatic phase I metabolites of chicoric acid. These three compounds had strong capacities for scavenging free radicals and had been demonstrated to increase intracellular ROS levels in 3T3-L1 preadipocytes, thereby reducing cell vitality. Finally, the pharmacological activities of chicoric acid were significantly stronger than those of its metabolites within a certain concentration range.

  9. The effect of fluid mechanical stress on cellular arachidonic acid metabolism

    NASA Technical Reports Server (NTRS)

    Mcintire, L. V.; Frangos, J. A.; Rhee, B. G.; Eskin, S. G.; Hall, E. R.

    1987-01-01

    The effect of sublytic levels of mechanical perturations of cells on cell metabolism were investigated by analyzing the products of arachidonic acid (used as a marker metabolite) in blood platelets, polymorphonuclear leucocytes, and cultured umbilical-vein endothelial cells after the suspensions of these cells were subjected to a shear stress in a modified viscometer. It is shown that the sublytic levels of mechanical stress stimulated the arachidonic acid metabolism in all these cell types. Possible biological implications of this stress-metabolism coupling are discussed.

  10. CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids123

    PubMed Central

    Lee, Yu-Chi; Shen, Jian; Parnell, Laurence D; Arnett, Donna K; Tsai, Michael Y; Lai, Chao-Qiang; Ordovas, Jose M

    2009-01-01

    Background: Disruption of the circadian system may be causal for manifestations of the metabolic syndrome (MetS). Objective: The objective was to study the associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid (FA) composition from dietary and red blood cell (RBC) membrane sources. Design: Participants (n = 1100) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study were included. Dietary intake was estimated with a validated questionnaire. Anthropometric and biochemical measurements and genotypes were determined. Postprandial lipids and the FA composition of RBC membranes were analyzed. Results: CLOCK single nucleotide polymorphisms were significantly associated with obesity and individual components of MetS. For single nucleotide polymorphism rs4580704, minor allele carriers had a 46% lower risk of hypertension than did noncarriers. The monounsaturated fatty acid (MUFA) content of RBC membranes, particularly oleic acid, changed according to CLOCK genetic variants (P < 0.05). We identified significant gene-diet interactions associated with MetS at the CLOCK locus. By dichotomizing MUFA intake, we found different effects across rs4580704 genotypes for glucose (P = 0.020) and insulin resistance (P = 0.026). The protective effect of the minor allele on insulin sensitivity was only present when MUFA intake was >13.2% of energy. We also found different effects across CLOCK 3111T→C genotypes for saturated fatty acid intake (% of energy) (P = 0.017). The deleterious effect of gene variants on waist circumference was only found with high saturated fatty acid intakes (>11.8%). Conclusions: CLOCK polymorphisms interact with FAs to modulate MetS traits. The dietary source and membrane content of MUFAs are implicated in the relations between alterations in the circadian system and MetS. PMID:19846548

  11. The Treatment of Gout and Disorders of Uric Acid Metabolism with Allopurinol

    PubMed Central

    Ogryzlo, M. A.; Urowitz, M. B.; Weber, H. M.; Houpt, J. B.

    1966-01-01

    Allopurinol (4-hydroxypyrazolo (3,4-d)-pyrimidine) is a potent xanthine oxidase inhibitor which inhibits the oxidation of naturally occurring oxypurines, thus decreasing uric acid formation. The clinical and metabolic effects of this agent were studied in 80 subjects with primary and secondary gout and other disorders of uric acid metabolism. Allopurinol has been universally successful in lowering the serum uric acid concentration and uric acid excretion to normal levels, while not significantly affecting the clearance of urate or other aspects of renal function. Oxypurine excretion increased concomitantly with the fall in urine uric acid. The agent is particularly valuable in the management of problems of gout with azotemia, acute uric acid nephropathy and uric acid urolithiasis. The minor side effects, clinical indications and theoretical complications are discussed. PMID:5923471

  12. Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu

    2017-01-01

    The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.

  13. Occurrence and metabolism of 7-hydroxy-2-indolinone-3-acetic acid in Zea mays

    NASA Technical Reports Server (NTRS)

    Lewer, P.; Bandurski, R. S.

    1987-01-01

    7-Hydroxy-2-indolinone-3-acetic acid was identified as a catabolite of indole-3-acetic acid in germinating kernels of Zea mays and found to be present in amounts of ca 3.1 nmol/kernel. 7-Hydroxy-2-indolinone-3-acetic acid was shown to be a biosynthetic intermediate between 2-indolinone-3-acetic acid and 7-hydroxy-2-indolinone-3-acetic acid-7'-O-glucoside in both kernels and roots of Zea mays. Further metabolism of 7-hydroxy-2-[5-3H]-indolinone-3-acetic acid-7'-O-glucoside occurred to yield tritiated water plus, as yet, uncharacterized products.

  14. The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

    PubMed Central

    Zeldin, D C; Plitman, J D; Kobayashi, J; Miller, R F; Snapper, J R; Falck, J R; Szarek, J L; Philpot, R M; Capdevila, J H

    1995-01-01

    Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung. Images PMID:7738183

  15. Circulating Unsaturated Fatty Acids Delineate the Metabolic Status of Obese Individuals

    PubMed Central

    Ni, Yan; Zhao, Linjing; Yu, Haoyong; Ma, Xiaojing; Bao, Yuqian; Rajani, Cynthia; Loo, Lenora W.M.; Shvetsov, Yurii B.; Yu, Herbert; Chen, Tianlu; Zhang, Yinan; Wang, Congrong; Hu, Cheng; Su, Mingming; Xie, Guoxiang; Zhao, Aihua; Jia, Wei; Jia, Weiping

    2015-01-01

    Background Obesity is not a homogeneous condition across individuals since about 25–40% of obese individuals can maintain healthy status with no apparent signs of metabolic complications. The simple anthropometric measure of body mass index does not always reflect the biological effects of excessive body fat on health, thus additional molecular characterizations of obese phenotypes are needed to assess the risk of developing subsequent metabolic conditions at an individual level. Methods To better understand the associations of free fatty acids (FFAs) with metabolic phenotypes of obesity, we applied a targeted metabolomics approach to measure 40 serum FFAs from 452 individuals who participated in four independent studies, using an ultra-performance liquid chromatograph coupled to a Xevo G2 quadruple time-of-flight mass spectrometer. Findings FFA levels were significantly elevated in overweight/obese subjects with diabetes compared to their healthy counterparts. We identified a group of unsaturated fatty acids (UFAs) that are closely correlated with metabolic status in two groups of obese individuals who underwent weight loss intervention and can predict the recurrence of diabetes at two years after metabolic surgery. Two UFAs, dihomo-gamma-linolenic acid and palmitoleic acid, were also able to predict the future development of metabolic syndrome (MS) in a group of obese subjects. Interpretation These findings underscore the potential role of UFAs in the MS pathogenesis and also as important markers in predicting the risk of developing diabetes in obese individuals or diabetes remission after a metabolic surgery. PMID:26629547

  16. Characterization of the metabolic interaction between trihalomethanes and chloroacetic acids using rat liver microsomes.

    PubMed

    St-Pierre, Annie; Krishnan, Kannan; Tardif, Robert

    2005-02-27

    The aim of this study was to investigate the in vitro metabolism of trihalomethanes (THMs) in the presence of trichloroacetic acid (TCA), dichloracetic acid (DCA), monochloroacetic acid (MCA), and 4-methylpyrazole (4-MP) using liver microsomes from male Sprague-Dawley rats. Using the vial equilibration technique, initial experiments were carried out with starting concentrations of approximately 40 ppm THMs and 12-22 mM chloroacetic acids. The results indicated a mutual metabolic inhibition between THMs present as binary or quaternary mixtures. Although DCA and MCA had no influence on THMs, TCA produced a marked inhibition of the metabolism of all THMs: chloroform (CHCl3) (55%), bromodichloromethane (BDCM) (34%), dibromochloromethane (DBCM) (30%), and bromoform (TBM) (23%). The presence of 4-MP also reduced THM metabolism, the importance of which decreased in the following order: CHCl3 > BDCM > DBCM = TBM. In further vial equilibration experiments, using 9-140 ppm as starting concentrations of THMs, enzyme kinetic parameters (i.e., Michaelis constant, K(m), and maximum velocity, V(max)) were determined both in the absence and in the presence of TCA (12.2 mM). Results are consistent with a competitive inhibition between TCA and CHCl3, whereas the metabolic inhibition of BDCM and TMB by TCA was non-competitive. As for DBCM, results suggest a more complex pattern of inhibition. These results suggest that CYP2E1 is involved in the metabolism of THMs as well as in the metabolic interaction between THMs and TCA.

  17. Lysophosphatidic acid synthesis and phospholipid metabolism in rat mast cells

    SciTech Connect

    Fagan, D.L.

    1986-01-01

    The role of lysophosphatidic acid in mast cell response to antigen was investigated using an isolated rat serosal mast cell model. The cells were incubated with monoclonal murine immunoglobulin E to the dinitrophenyl hapten and prelabeled with /sup 32/P-orthophosphate or /sup 3/H-fatty acids. Lysophosphatidic acid was isolated form cell extracts by 2-dimensional thin-layer chromatography, and the incorporated radioactivity was assessed by liquid scintillation counting. Lysophosphatidic acid labeling with /sup 32/P was increased 2-4 fold within 5 minutes after the addition of antigen or three other mast cell agonists. Functional group analyses unequivocally showed that the labeled compound was lysophosphatidic acid. Lysophosphatidic acid synthesis was dependent on the activity of diacylglycerol lipase, suggesting formation from monoacylglycerol. In addition, the studies of lysophosphatidic acid synthesis suggest that the addition of antigen to mast cells may initiate more than one route of phospholipid degradation and resynthesis. Whatever the origin of lysophosphatidic acid, the results of this study demonstrated that lysophosphatidic acid synthesis is stimulated by a variety of mast cell agonists. Dose-response, kinetic, and pharmacologic studies showed close concordance between histamine release and lysophosphatidic acid labeling responses. These observations provide strong evidence that lysophosphatidic acid plays an important role in mast cell activation.

  18. Soybean Aphid Infestation Induces Changes in Fatty Acid Metabolism in Soybean

    PubMed Central

    Kanobe, Charles; McCarville, Michael T.; O’Neal, Matthew E.; Tylka, Gregory L.; MacIntosh, Gustavo C.

    2015-01-01

    The soybean aphid (Aphis glycines Matsumura) is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fatty acids play in jasmonate-induced plant defenses, we analyzed the fatty acid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fatty acids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fatty acids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fatty acid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fatty acids, linolenic acid, is the precursor of jasmonate; thus, these changes in fatty acid metabolism may be examples of “metabolic hijacking” by the aphid to avoid the induction of effective defenses. Based on the changes in fatty acid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fatty acid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fatty acids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor. PMID:26684003

  19. Latitudinal variation in the degree of crassulacean acid metabolism in Puya chilensis.

    PubMed

    Quezada, I M; Zotz, G; Gianoli, E

    2014-07-01

    Crassulacean acid metabolism (CAM) is a photosynthetic pathway found in many plant species from arid and semiarid environments. Few studies aiming to characterise plant species as CAM or C3 account for inter-population differences in photosynthetic pathway, often relying on samples taken from herbarium material and/or a single plant or population. This may be especially problematic for species growing under contrasting climate conditions, as is the case for species with a wide geographic range. We used Puya chilensis, a species previously reported as CAM and C3, to study among-population variation in expression of the CAM pathway within its distribution range, which spans a significant climate gradient. We carried out a wide sampling scheme, including five populations and a combination of analytical methods (quantification of nocturnal acidification and stable isotope measurements). The study populations of P. chilensis encompass the entire latitudinal distribution range, from semi-arid to temperate oceanic climates. Our results indicate that CAM decreased with latitude. However, even in the southern (wetter) populations, where δ13C values were indicative of C3 metabolism, we found some nocturnal acidification. We stress the value of using two methods along with the use of samples from different populations, as this allows more reliable conclusions on the photosynthetic pathway for 'probable' CAM species that face varying climate conditions within their distribution ranges.

  20. Metabolic flux responses to genetic modification for shikimic acid production by Bacillus subtilis strains

    PubMed Central

    2014-01-01

    Background Shikimic acid (SA) is a key chiral starting molecule for the synthesis of the neuramidase inhibitor GS4104 against viral influenza. Microbial production of SA has been extensively investigated in Escherichia coli, and to a less extent in Bacillus subtilis. However, metabolic flux of the high SA-producing strains has not been explored. In this study, we constructed with genetic manipulation and further determined metabolic flux with 13C-labeling test of high SA-producing B. subtilis strains. Results B. subtilis 1A474 had a mutation in SA kinase gene (aroI) and accumulated 1.5 g/L of SA. Overexpression of plasmid-encoded aroA, aroB, aroC or aroD in B. subtilis revealed that aroD had the most significantly positive effects on SA production. Simultaneous overexpression of genes for 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (aroA) and SA dehydrogenase (aroD) in B. subtilis BSSA/pSAAroA/pDGSAAroD resulted in SA production of 3.2 g/L. 13C-Metabolic flux assay (MFA) on the two strains BSSA/pHCMC04/pDG148-stu and BSSA/pSAAroA/pDGSAAroD indicated the carbon flux from glucose to SA increased to 4.6% in BSSA/pSAAroA/pDGSAAroD from 1.9% in strain BSSA/pHCMC04/pDG148-stu. The carbon flux through tricarboxylic acid cycle significantly reduced, while responses of the pentose phosphate pathway and the glycolysis to high SA production were rather weak, in the strain BSSA/pSAAroA/pDGSAAroD. Based on the results from MFA, two potential targets for further optimization of SA production were identified. Experiments on genetic deletion of phosphoenoylpyruvate kinase gene confirmed its positive influence on SA production, while the overexpression of the transketolase gene did not lead to increase in SA production. Conclusion Of the genes involved in shikimate pathway in B. subtilis, aroD exerted most significant influence on SA accumulation. Overexpression of plasmid-encoded aroA and aroD doubled SA production than its parent strain. MFA revealed metabolic flux

  1. Red blood cell fatty acid composition and the metabolic syndrome: NHLBI GOLDN study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Different fatty acids may vary in their effect on the metabolic syndrome (MetS). We tested whether fatty acid classes measured in red blood cells (RBC) are associated with the MetS or its components. Included were men (n=497, 49+/-16 y) and women (n=539, 48+/-16 y) from 187 families in the Genetics ...

  2. Intestinal bile acid sensing is linked to key endocrine and metabolic signalng pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bile acids have historically been considered to mainly function in cholesterol homeostasis and facilitate fat digestion in the gastrointestinal tract. Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G prote...

  3. Metabolism of fatty acids in rat brain in microsomal membranes

    SciTech Connect

    Aeberhard, E.E.; Gan-Elepano, M.; Mead, J.F.

    1980-01-01

    Using a technique in which substrate fatty acids are incorporated into microsomal membranes followd by comparison of their rates of desaturation or elongation with those of exogenous added fatty acids it has been found that the desaturation rate is more rapid for the membrane-bound substrate than for the added fatty acid. Moreover, the product of the membrane-bound substrate is incorporated into membrane phospholipid whereas the product of the exogenous substrate is found in di- and triacyl glycerols and in free fatty acids as well. These and other findings point to a normal sequence of reaction of membrane liqids with membrane-bound substrates involving transfer of fatty acid from phospholipid to the coupled enzyme systems without ready equilibration with the free fatty acid pool.

  4. Changes in primary metabolism leading to citric acid overflow in Aspergillus niger.

    PubMed

    Legisa, Matic; Mattey, Michael

    2007-02-01

    For citric acid-accumulating Aspergillus niger cells, the enhancement of anaplerotic reactions replenishing tricarboxylic acid cycle intermediates predisposes the cells to form the product. However, there is no increased citrate level in germinating spores and a complex sequence of developmental events is needed to change the metabolism in a way that leads to an increased level of tricarboxylic acid cycle intermediates in mycelia. A review of physiological events that cause such intracellular conditions, with the special emphasis on the discussion of hexose transport into the cells and regulation of primary metabolism, predominantly of glycolytic flux during the process, is presented.

  5. Ascorbate metabolism and the developmental demand for tartaric and oxalic acids in ripening grape berries

    PubMed Central

    2009-01-01

    Background Fresh fruits are well accepted as a good source of the dietary antioxidant ascorbic acid (Asc, Vitamin C). However, fruits such as grapes do not accumulate exceptionally high quantities of Asc. Grapes, unlike most other cultivated fruits do however use Asc as a precursor for the synthesis of both oxalic (OA) and tartaric acids (TA). TA is a commercially important product in the wine industry and due to its acidifying effect on crushed juice it can influence the organoleptic properties of the wine. Despite the interest in Asc accumulation in fruits, little is known about the mechanisms whereby Asc concentration is regulated. The purpose of this study was to gain insights into Asc metabolism in wine grapes (Vitis vinifera c.v. Shiraz.) and thus ascertain whether the developmental demand for TA and OA synthesis influences Asc accumulation in the berry. Results We provide evidence for developmentally differentiated up-regulation of Asc biosynthetic pathways and subsequent fluctuations in Asc, TA and OA accumulation. Rapid accumulation of Asc and a low Asc to dehydroascorbate (DHA) ratio in young berries was co-ordinated with up-regulation of three of the primary Asc biosynthetic (Smirnoff-Wheeler) pathway genes. Immature berries synthesised Asc in-situ from the primary pathway precursors D-mannose and L-galactose. Immature berries also accumulated TA in early berry development in co-ordination with up-regulation of a TA biosynthetic gene. In contrast, ripe berries have up-regulated expression of the alternative Asc biosynthetic pathway gene D-galacturonic acid reductase with only residual expression of Smirnoff-Wheeler Asc biosynthetic pathway genes and of the TA biosynthetic gene. The ripening phase was further associated with up-regulation of Asc recycling genes, a secondary phase of increased accumulation of Asc and an increase in the Asc to DHA ratio. Conclusion We demonstrate strong developmental regulation of Asc biosynthetic, recycling and catabolic

  6. Changes in arachidonic acid metabolism in UV-irradiated hairless mouse skin

    SciTech Connect

    Ruzicka, T.; Walter, J.F.; Printz, M.P.

    1983-10-01

    This study was conducted to investigate the metabolism of arachidonic acid in the skin of hairless mice exposed to UVA, PUVA, UVB, and UVC irradiation. The main products of arachidonic acid in the epidermis were hydroxyeicosatetraenoic acid (HETE), PGE2, and PGD2. Dermis displayed a lower lipoxygenase activity (expressed as HETE production) than the epidermis and showed no detectable cyclooxygenase activity, i.e., no prostaglandin production. The main changes observed in UV-induced inflammatory reactions were as follows. 1. A 5-fold increase in dermal HETE production in PUVA-treated animals and a 29% reduction in epidermal HETE formation after UVC treatment. 2. A marked decrease of PGD2 and a marked increase of PGE2 formation due to alterations of PGH2 metabolism in the UVB-treated group; however, cyclooxygenase activity was unchanged. These changes in arachidonic acid metabolism in the skin may be of pathophysiologic importance in UV-induced inflammatory reaction.

  7. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder.

    PubMed

    McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Stanford, Kevin E; Hahn, Chang-Gyu; Richtand, Neil M

    2008-09-30

    Previous antemortem and postmortem tissue fatty acid composition studies have observed significant deficits in the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3) in red blood cell (RBC) and postmortem cortical membranes of patients with unipolar depression. In the present study, we determined the fatty acid composition of postmortem orbitofrontal cortex (OFC, Brodmann area 10) of patients with bipolar disorder (n=18) and age-matched normal controls (n=19) by gas chromatography. After correction for multiple comparisons, DHA (-24%), arachidonic acid (-14%), and stearic acid (C18:0) (-4.5%) compositions were significantly lower, and cis-vaccenic acid (18:1n-7) (+12.5%) composition significantly higher, in the OFC of bipolar patients relative to normal controls. Based on metabolite:precursor ratios, significant elevations in arachidonic acid, stearic acid, and palmitic acid conversion/metabolism were observed in the OFC of bipolar patients, and were inversely correlated with DHA composition. Deficits in OFC DHA and arachidonic acid composition, and elevations in arachidonic acid metabolism, were numerically (but not significantly) greater in drug-free bipolar patients relative to patients treated with mood-stabilizer or antipsychotic medications. OFC DHA and arachidonic acid deficits were greater in patients plus normal controls with high vs. low alcohol abuse severity. These results add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of bipolar disorder.

  8. 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

    2017-04-06

    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.

  9. Integrated Transcriptome and Metabolic Analyses Reveals Novel Insights into Free Amino Acid Metabolism in Huangjinya Tea Cultivar

    PubMed Central

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-01-01

    The chlorotic tea variety Huangjinya, a natural mutant, contains enhanced levels of free amino acids in its leaves, which improves the drinking quality of its brewed tea. Consequently, this chlorotic mutant has a higher economic value than the non-chlorotic varieties. However, the molecular mechanisms behind the increased levels of free amino acids in this mutant are mostly unknown, as are the possible effects of this mutation on the overall metabolome and biosynthetic pathways in tea leaves. To gain further insight into the effects of chlorosis on the global metabolome and biosynthetic pathways in this mutant, Huangjinya plants were grown under normal and reduced sunlight, resulting in chlorotic and non-chlorotic leaves, respectively; their leaves were analyzed using transcriptomics as well as targeted and untargeted metabolomics. Approximately 5,000 genes (8.5% of the total analyzed) and ca. 300 metabolites (14.5% of the total detected) were significantly differentially regulated, thus indicating the occurrence of marked effects of light on the biosynthetic pathways in this mutant plant. Considering primary metabolism, including that of sugars, amino acids, and organic acids, significant changes were observed in the expression of genes involved in both nitrogen (N) and carbon metabolism. The suite of changes not only generated an increase in amino acids, including glutamic acid, glutamine, and theanine, but it also elevated the levels of free ammonium, citrate, and α-ketoglutarate, and lowered the levels of mono- and di-saccharides and of caffeine as compared with the non-chlorotic leaves. Taken together, our results suggest that the increased levels of amino acids in the chlorotic vs. non-chlorotic leaves are likely due to increased protein catabolism and/or decreased glycolysis and diminished biosynthesis of nitrogen-containing compounds other than amino acids, including chlorophyll, purines, nucleotides, and alkaloids. PMID:28321230

  10. Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients

    PubMed Central

    Denny, Gerald B.; Deger, Serpil M.; Chen, Guanhua; Bian, Aihua; Sha, Feng; Booker, Cindy; Kesler, Jaclyn T.; David, Sthuthi; Ellis, Charles D.; Ikizler, T. Alp

    2016-01-01

    Background Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients. Methods We examined 35 MHD patients and 17 control subjects with normal kidney function by hyperinsulinemic-euglycemic clamp (HEGC) followed by HEAC clamp procedure to obtain leucine disposal rate (LDR) along with isotope tracer methodology to assess whole body protein turnover. Results The glucose disposal rate (GDR) by HEGC was 5.1 ± 2.1 mg/kg/min for the MHD patients compared to 6.3 ± 3.9 mg/kg/min for the controls (p = 0.38). The LDR during HEAC was 0.09 ± 0.03 mg/kg/min for the MHD patients compared to 0.11 ± 0.05 mg/kg/min for the controls (p = 0.009). The LDR level was correlated with whole body protein synthesis (r = 0.25; p = 0.08), with whole body protein breakdown (r = −0.38 p = 0.01) and net protein balance (r = 0.85; p < 0.001) in the overall study population. Correlations remained significant in subgroup analysis. The GDR derived by HEGC and LDR correlated well in the controls (r = 0.79, p < 0.001), but less so in the MHD patients (r = 0.58, p < 0.001). Conclusions Leucine disposal rate reliably measures amino acid utilization in MHD patients and controls in response to high dose insulin. PMID:27413537

  11. Fatty acid biosynthesis revisited: Structure elucidation and metabolic engineering

    DOE PAGES

    Beld, Joris; Lee, D. John; Burkart, Michael D.

    2014-10-20

    Fatty acids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fatty acid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fatty acid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fatty acid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fatty acids or specific high value products. Such efforts require a fundamental understandingmore » of the enzymatic activities and regulation of fatty acid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fatty acid synthases' many intricate structural and regulatory elements. Lastly, in this review, we summarize each enzymatic domain and discuss efforts to engineer fatty acid synthases, providing some clues to important challenges and opportunities in the field.« less

  12. Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid.

    PubMed

    Homann, Arne; Qamar, Riaz-Ul; Serim, Sevnur; Dersch, Petra; Seibel, Jürgen

    2010-03-08

    Sialic acids are located at the termini of mammalian cell-surface glycostructures, which participate in essential interaction processes including adhesion of pathogens prior to infection and immunogenicity. Here we present the synthesis and bioorthogonal metabolic incorporation of the sialic acid analogue N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex) into the cell-surface glycocalyx of a human larynx carcinoma cell line (HEp-2) and its fluorescence labelling by click chemistry.

  13. An integrated metabonomics and transcriptomics approach to understanding metabolic pathway disturbance induced by perfluorooctanoic acid.

    PubMed

    Peng, Siyuan; Yan, Lijuan; Zhang, Jie; Wang, Zhanlin; Tian, Meiping; Shen, Heqing

    2013-12-01

    Perfluorooctanoic acid (PFOA) is one of the most representative perfluorinated compounds and liver is the major organ where PFOA is accumulated. Although the multiple toxicities had been reported, its toxicological profile remained unclear. In this study, a systems toxicology strategy integrating liquid chromatography/mass spectrometry-based metabonomics and transcriptomics analyses was applied for the first time to investigate the effects of PFOA on a representative Chinese normal human liver cell line L-02, with focusing on the metabolic disturbance. Fifteen potential biomarkers were identified on metabolic level and most observations were consistent with the altered levels of gene expression. Our results showed that PFOA induced the perturbations in various metabolic processes in L-02 cells, especially lipid metabolism-related pathways. The up-stream mitochondrial carnitine metabolism was proved to be influenced by PFOA treatment. The specific transformation from carnitine to acylcarnitines, which showed a dose-dependent effect, and the expression level of key genes involved in this pathway were observed to be altered correspondingly. Furthermore, the down-stream cholesterol biosynthesis was directly confirmed to be up-regulated by both increased cholesterol content and elevated expression level of key genes. The PFOA-induced lipid metabolism-related effects in L-02 cells started from the fatty acid catabolism in cytosol, fluctuated to the processes in mitochondria, extended to the cholesterol biosynthesis. Many other metabolic pathways like amino acid metabolism and tricarboxylic acid cycle might also be disturbed. The findings obtained from the systems biological research provide more details about metabolic disorders induced by PFOA in human liver.

  14. Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids.

    PubMed

    Kondo, Natsuki; Ohno, Yusuke; Yamagata, Maki; Obara, Takashi; Seki, Naoya; Kitamura, Takuya; Naganuma, Tatsuro; Kihara, Akio

    2014-10-27

    The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an ~40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.

  15. Hepatocyte nuclear factor 4α regulation of bile acid and drug metabolism

    PubMed Central

    Chiang, John YL

    2013-01-01

    The hepatocyte nuclear factor 4α (HNF4α) is a liver-enriched nuclear receptor that plays a critical role in early morphogenesis, fetal liver development, liver differentiation and metabolism. Human HNF4α gene mutations cause maturity on-set diabetes of the young type 1, an autosomal dominant non-insulin-dependent diabetes mellitus. HNF4α is an orphan nuclear receptor because of which the endogenous ligand has not been firmly identified. The trans-activating activity of HNF4α is enhanced by interacting with co-activators and inhibited by corepressors. Recent studies have revealed that HNF4α plays a central role in regulation of bile acid metabolism in the liver. Bile acids are required for biliary excretion of cholesterol and metabolites, and intestinal absorption of fat, nutrients, drug and xenobiotics for transport and distribution to liver and other tissues. Bile acids are signaling molecules that activate nuclear receptors to control lipids and drug metabolism in the liver and intestine. Therefore, HNF4α plays a central role in coordinated regulation of bile acid and xenobiotics metabolism. Drugs that specifically activate HNF4α could be developed for treating metabolic diseases such as diabetes, dyslipidemia and cholestasis, as well as drug metabolism and detoxification. PMID:19239393

  16. The Mediterranean diet: effects on proteins that mediate fatty acid metabolism in the colon.

    PubMed

    Djuric, Zora

    2011-12-01

    A Mediterranean diet appears to have health benefits in many domains of human health, mediated perhaps by its anti-inflammatory effects. Metabolism of fatty acids and subsequent eicosanoid production is a key mechanism by which a Mediterranean diet can exert anti-inflammatory effects. Both dietary fatty acids and fatty acid metabolism determine fatty acid availability for cyclooxygenase- and lipoxygenase-dependent production of eicosanoids, namely prostaglandins and leukotrienes. In dietary intervention studies and in observational studies of the Mediterranean diet, blood levels of fatty acids do reflect dietary intakes but are attenuated. Small differences in fatty acid levels, however, appear to be important, especially when exposures occur over long periods of time. This review summarizes how fat intakes from a Greek-style Mediterranean diet can be expected to affect fatty acid metabolizing proteins, with an emphasis on the metabolic pathways that lead to the formation of proinflammatory eicosanoids. The proteins involved in these pathways are ripe for investigation using proteomic approaches and may be targets for colon cancer prevention.

  17. Ascorbic acid requirements and metabolism in relation to organochlorine pesticides.

    PubMed

    Street, J C; Chadwick, R W

    1975-09-30

    Those organochlorine pesticides which possess both high lipoid solubility and high resistance to biodegradation are prone to accumulation in animal tissues and produce relatively long-term effects as toxicants. Such compounds, typified by DDT, Dieldrin, and Lindane, are profound inducers of hepatic microsomal enzymes, including parts of the glucuronic acid and ascorbic acid biosynthetic pathways. Consequently, administering such pesticides to rats in accompanied by enhanced formation and excretion of D-glucuronic acid and L-ascorbic acid, or D-glucaric acid in the case of guinea pigs. Secondarily, the efficiency in biodegrading the pesticides is reduced in ascorbic-acid-deficient guinea pigs with correspondingly greater residue accumulation in tissue. This would aggravate chronic toxic effects of the compounds. Finally, the capacity of the liver to adapt to the presence of such toxicants through enhanced microsomal enzymatic levels appears to be sensitive to its ascorbate status. Impaired enzyme induction is apparent quite early during ascorbic acid depletion in guinea pigs. The enhanced turnover of ascorbate produced by such pesticides, the poor enzymatic adaptation to them during ascorbate depletion and the dependency of the oxidase system upon adequate ascorbate, all point to the central significance of ascorbate status in the liver, and possibly other tissues, as a determinant of their chronic toxicity.

  18. Availability of water controls Crassulacean acid metabolism in succulents of the Richtersveld (Namib desert, South Africa).

    PubMed

    von Willert, D J; Brinckmann, E; Scheitler, B; Eller, B M

    1985-05-01

    Features of Crassulacean acid metabolism (CAM) were studied in a variety of different succulents in response to climatic conditions between March 1977 and October 1983 in the southern Namib desert (Richtersveld). A screening in 1977 and 1978 revealed that nearly all investigated succulents performed a CAM, but overnight accumulation of malate declined gradually with decreasing soil water potential, tissue osmotic potential, and leaf water content. This was further substantiated by an extended period of insufficient rainfall in 1979 and 1980 which damaged the evergreen CAM succulents between 80 and 100%. In most of the species still living, neither CO2-gas exchange nor diurnal acid fluctuation, indicative of CAM, could be detected unless an abundant rainfall restored both CAM features. Plants persisted in a stage of latent life.Water supply is one necessary prerequisite for CAM in the Richtersveld. But even well-watered plants with CAM were sensitive to short-term water stress caused by high water-vapour partialpressure deficit (VPD) in the night, which reduced or prevented CO2 uptake and resulted in a linear relation between overnight accumulated malate and VPD. The results do not support the opinion that, for the Namib succulents, CAM is an adaptive mechanism to water stress since long-term and short-term water stress stopped nocturnal malate synthesis, but instead lead to the conclusion that nocuturnal CO2 fixation is only performed when the water status of the plant can be improved simultaneously.

  19. Metabolism of parabens (4-hydroxybenzoic acid esters) by hepatic esterases and UDP-glucuronosyltransferases in man.

    PubMed

    Abbas, Suzanne; Greige-Gerges, Hélène; Karam, Nancy; Piet, Marie-Hélène; Netter, Patrick; Magdalou, Jacques

    2010-01-01

    Parabens (alkyl esters of 4-hydroxybenzoic acid) are widely used as preservatives in drugs, cosmetic products, and foodstuffs. Safety concerns have recently increased due to the potential health risks associated to exposure to large amounts of these substances. Biotransformation of parabens mainly includes hydrolysis of the ester bond and glucuronidation reactions. The hydrolysis and glucuronidation of a series of six parabens differing by the nature of the alkyl group were investigated in human liver microsomes and plasma, and the major human UDP-glucuronosyltransferase (UGT) isoforms involved in the reaction were identified. Methyl- and ethylparaben were stable in human plasma, with 95% of the initial concentration remaining after 24 h. On the other hand, propyl-, butyl- and benzylparaben concentrations decreased by 50% under similar conditions. In contrast, rapid hydrolysis was measured with human liver microsomes depending on the alkyl chain length, with t(1/2) varying from 22 min for methylparaben to 87 min for butylparaben. All parabens were actively glucuronidated by liver microsomes, in comparison to 4-hydroxybenzoic acid. They were mainly substrates of human recombinant UGT1A1, UGT1A8, UGT1A9, UGT2B7, UGT2B15 and UGT2B17. In conclusion, the parabens were readily metabolized in human liver through esterase hydrolysis and glucuronidation by several UGT isoforms. These results suggest that these parabens do not accumulate in human tissue.

  20. Characterization of arachidonic acid metabolism by rat cytochrome P450 enzymes: the involvement of CYP1As.

    PubMed

    El-Sherbeni, Ahmed A; El-Kadi, Ayman O S

    2014-09-01

    Cytochrome P450 (P450) enzymes mediate arachidonic acid (AA) oxidation to several biologically active metabolites. Our aims in this study were to characterize AA metabolism by different recombinant rat P450 enzymes and to identify new targets for modulating P450-AA metabolism in vivo. A liquid chromatography-mass spectrometry method was developed and validated for the simultaneous measurements of AA and 15 of its P450 metabolites. CYP1A1, CYP1A2, CYP2B1, CYP2C6, and CYP2C11 were found to metabolize AA with high catalytic activity, and CYP2A1, CYP2C13, CYP2D1, CYP2E1, and CYP3A1 had lower activity. CYP1A1 and CYP1A2 produced ω-1→4 hydroxyeicosatetraenoic acids (HETEs) as 88.7 and 62.7%, respectively, of the total metabolites formed. CYP2C11 produced epoxyeicosatrienoic acids (EETs) as 61.3%, and CYP2C6 produced midchain HETEs and EETs as 48.3 and 29.4%, respectively, of the total metabolites formed. The formation of CYP1A1, CYP1A2, CYP2C6, and CYP2C11 major metabolites followed an atypical kinetic profile of substrate inhibition. CYP1As inhibition by α-naphthoflavone or anti-CYP1As antibodies significantly reduced ω-1→4 HETE formation in the lungs and liver, whereas CYP1As induction by 3-methylcholanthrene resulted in a significant increase in ω-1→4 HETEs formation in the heart, lungs, kidney, and livers by 370, 646, 532, and 848%, respectively. In conclusion, our results suggest that CYP1As and CYP2Cs are major players in the metabolism of AA. The significant contribution of CYP1As to AA metabolism and their strong inducibility suggest their possible use as targets for the prevention and treatment of several diseases.

  1. Metabolic characteristics of dominant microbes and key rare species from an acidic hot spring in Taiwan revealed by metagenomics

    SciTech Connect

    Lin, Kuei -Han; Liao, Ben -Yang; Chang, Hao -Wei; Huang, Shiao -Wei; Chang, Ting -Yan; Yang, Cheng -Yu; Wang, Yu -Bin; Lin, Yu-Teh Kirk; Wu, Yu -Wei; Tang, Sen -Lin; Yu, Hon -Tsen

    2015-12-03

    Microbial diversity and community structures in acidic hot springs have been characterized by 16S rRNA gene-based diversity surveys. However, our understanding regarding the interactions among microbes, or between microbes and environmental factors, remains limited. In the present study, a metagenomic approach, followed by bioinformatics analyses, were used to predict interactions within the microbial ecosystem in Shi-Huang-Ping (SHP), an acidic hot spring in northern Taiwan. Characterizing environmental parameters and potential metabolic pathways highlighted the importance of carbon assimilatory pathways. Four distinct carbon assimilatory pathways were identified in five dominant genera of bacteria. Of those dominant carbon fixers, Hydrogenobaculum bacteria outcompeted other carbon assimilators and dominated the SHP, presumably due to their ability to metabolize hydrogen and to withstand an anaerobic environment with fluctuating temperatures. Furthermore, most dominant microbes were capable of metabolizing inorganic sulfur-related compounds (abundant in SHP). However, Acidithiobacillus ferrooxidans was the only species among key rare microbes with the capability to fix nitrogen, suggesting a key role in nitrogen cycling. In addition to potential metabolic interactions, based on the 16S rRNAs gene sequence of Nanoarchaeum-related and its potential host Ignicoccus-related archaea, as well as sequences of viruses and CRISPR arrays, we inferred that there were complex microbe-microbe interactions. In conclusion, our study provided evidence that there were numerous microbe-microbe and microbe-environment interactions within the microbial community in an acidic hot spring. We proposed that Hydrogenobaculum bacteria were the dominant microbial genus, as they were able to metabolize hydrogen, assimilate carbon and live in an anaerobic environment with fluctuating temperatures.

  2. Metabolic characteristics of dominant microbes and key rare species from an acidic hot spring in Taiwan revealed by metagenomics

    DOE PAGES

    Lin, Kuei -Han; Liao, Ben -Yang; Chang, Hao -Wei; ...

    2015-12-03

    Microbial diversity and community structures in acidic hot springs have been characterized by 16S rRNA gene-based diversity surveys. However, our understanding regarding the interactions among microbes, or between microbes and environmental factors, remains limited. In the present study, a metagenomic approach, followed by bioinformatics analyses, were used to predict interactions within the microbial ecosystem in Shi-Huang-Ping (SHP), an acidic hot spring in northern Taiwan. Characterizing environmental parameters and potential metabolic pathways highlighted the importance of carbon assimilatory pathways. Four distinct carbon assimilatory pathways were identified in five dominant genera of bacteria. Of those dominant carbon fixers, Hydrogenobaculum bacteria outcompeted othermore » carbon assimilators and dominated the SHP, presumably due to their ability to metabolize hydrogen and to withstand an anaerobic environment with fluctuating temperatures. Furthermore, most dominant microbes were capable of metabolizing inorganic sulfur-related compounds (abundant in SHP). However, Acidithiobacillus ferrooxidans was the only species among key rare microbes with the capability to fix nitrogen, suggesting a key role in nitrogen cycling. In addition to potential metabolic interactions, based on the 16S rRNAs gene sequence of Nanoarchaeum-related and its potential host Ignicoccus-related archaea, as well as sequences of viruses and CRISPR arrays, we inferred that there were complex microbe-microbe interactions. In conclusion, our study provided evidence that there were numerous microbe-microbe and microbe-environment interactions within the microbial community in an acidic hot spring. We proposed that Hydrogenobaculum bacteria were the dominant microbial genus, as they were able to metabolize hydrogen, assimilate carbon and live in an anaerobic environment with fluctuating temperatures.« less

  3. Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex.

    PubMed

    Cancelier, Kizzy; Gomes, Lara M; Carvalho-Silva, Milena; Teixeira, Letícia J; Rebelo, Joyce; Mota, Isabella T; Arent, Camila O; Mariot, Edemilson; Kist, Luiza W; Bogo, Maurício R; Quevedo, João; Scaini, Giselli; Streck, Emilio L

    2016-05-31

    Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.

  4. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  5. Amino acid metabolism of experimental granulation tissue in vitro.

    PubMed

    Aalto, M; Lampiaho, K; Pikkarainen, J; Kulonen, E

    1973-04-01

    1. The intracellular volume in granulation tissue was about 15% of the total urea space. 2. The experimental granuloma has a greater ability to retain amino acids during the proliferation phase than later during the synthesis of collagen. 3. The synthesis of collagen and other proteins by granulation tissue is related to the concentrations of proline and glutamic acid in the medium. 4. The rate of synthesis of proline from glutamic acid in granulation-tissue slices is greatest during collagen synthesis. It is enhanced by lactate. 5. Extracellular cations influence the synthesis of collagen and ouabain is inhibitory. Synthesis of other proteins is less sensitive in this respect. 6. It is suggested that the synthesis of collagen is related to the supply of certain amino acids, especially proline, and hence to the redox balance, and also to the function of the cell wall.

  6. Phytic Acid Metabolism in Lily (Lilium longiflorum Thunb.) Pollen 1

    PubMed Central

    Lin, Jih-Jing; Dickinson, David B.; Ho, Tuan-Hua David

    1987-01-01

    The accumulation of phytic acid during development of lily (Lilium longiflorum Thunb.) pollen and its degradation during germination have been studied. A substantial amount of phytic acid accumulates in lily pollen by 5 days before anthesis, and little change occurs during subsequent maturation. Mature lily pollen contains 7 to 8 micrograms phytic acid per milligram pollen. Considerable degradation of phytic acid occurs by 15 minutes of incubation in glucose culture medium, and very little is left by 3 hours. No partially phosphorylated myo-inositol accumulates during germination. The breakdown of phytic acid proceeds at a constant rate during this time period. The rate is calculated to be 0.037 microgram phytic acid/milligram pollen/minute. Two phytases are detected in germinated lily pollen extract using high performance liquid chromatography with an anion exchange column (diethylaminoethyl-5PW). The results suggest that one of the phytases is already present in mature ungerminated lily pollen and the other one is newly synthesized during germination from a long-lived, pre-existing mRNA. PMID:16665258

  7. Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia.

    PubMed

    Siekmeyer, Manuela; Petzold-Quinque, Stefanie; Terpe, Friederike; Beblo, Skadi; Gebhardt, Rolf; Schlensog-Schuster, Franziska; Kiess, Wieland; Siekmeyer, Werner

    2013-01-01

    The tricarboxylic acid (TCA) cycle represents the key enzymatic steps in cellular energy metabolism. Once the TCA cycle is impaired in case of inherited metabolic disorders, life-threatening episodes of metabolic decompensation and severe organ failure can arise. We present the case of a 6 ½-year-old girl with propionic acidaemia during an episode of acute life-threatening metabolic decompensation and severe lactic acidosis. Citric acid given as an oral formulation showed the potential to sustain the TCA cycle flux. This therapeutic approach may become a treatment option in a situation of acute metabolic crisis, possibly preventing severe disturbance of energy metabolism.

  8. Seasonal Patterns of Acid Metabolism and Gas Exchange in Opuntia basilaris1

    PubMed Central

    Szarek, Stan R.; Ting, Irwin P.

    1974-01-01

    Acid metabolism and gas exchange studies were conducted in situ on the cactus Opuntia basilaris Engelm. and Bigel. A pattern of significant seasonal variation was evident. The pattern was controlled by rainfall, which significantly influenced plant water potentials, total gas transfer resistances, and nocturnal organic acid synthesis. In winter and early spring, when plant water stress was mild, stomatal and mesophyll resistances remained low, permitting enhanced nocturnal assimilation of 14CO2. The day/night accumulation of acidity was large during these seasons. In summer and fall, plant water stress was moderate, although soil water stress was severe. The nocturnal assimilation of 14CO2 was very low during these seasons, even in stems with open stomata, indicating large mesophyll resistances restricting exogenous gas incorporation. The day/night accumulation of acidity was reduced, and a low level of acid metabolism persisted throughout this period. The rapid response to a midsummer rainfall emphasizes the importance of plant water potential as a parameter controlling over-all metabolic activity. The seasonal variations of acid metabolism and gas exchange significantly influenced the efficiency of water use and carbon dioxide assimilation. Periods of maximal efficiency followed rainfall throughout the course of the year. PMID:16658842

  9. Key roles of microsymbiont amino acid metabolism in rhizobia-legume interactions.

    PubMed

    Dunn, Michael Frederick

    2015-01-01

    Rhizobia are bacteria in the α-proteobacterial genera Rhizobium, Sinorhizobium, Mesorhizobium, Azorhizobium and Bradyrhizobium that reduce (fix) atmospheric nitrogen in symbiotic association with a compatible host plant. In free-living and/or symbiotically associated rhizobia, amino acids may, in addition to their incorporation into proteins, serve as carbon, nitrogen or sulfur sources, signals of cellular nitrogen status and precursors of important metabolites. Depending on the rhizobia-host plant combination, microsymbiont amino acid metabolism (biosynthesis, transport and/or degradation) is often crucial to the establishment and maintenance of an effective nitrogen-fixing symbiosis and is intimately interconnected with the metabolism of the plant. This review summarizes past findings and current research directions in rhizobial amino acid metabolism and evaluates the genetic, biochemical and genome expression studies from which these are derived. Specific sections deal with the regulation of rhizobial amino acid metabolism, amino acid transport, and finally the symbiotic roles of individual amino acids in different plant-rhizobia combinations.

  10. Improving Fatty Acid Availability for Bio-Hydrocarbon Production in Escherichia coli by Metabolic Engineering

    PubMed Central

    Lin, Fengming; Chen, Yu; Levine, Robert; Lee, Kilho; Yuan, Yingjin; Lin, Xiaoxia Nina

    2013-01-01

    Previous studies have demonstrated the feasibility of producing fatty-acid-derived hydrocarbons in Escherichia coli. However, product titers and yields remain low. In this work, we demonstrate new methods for improving fatty acid production by modifying central carbon metabolism and storing fatty acids in triacylglycerol. Based on suggestions from a computational model, we deleted seven genes involved in aerobic respiration, mixed-acid fermentation, and glyoxylate bypass (in the order of cyoA, nuoA, ndh, adhE, dld, pta, and iclR) to modify the central carbon metabolic/regulatory networks. These gene deletions led to increased total fatty acids, which were the highest in the mutants containing five or six gene knockouts. Additionally, when two key enzymes in the fatty acid biosynthesis pathway were over-expressed, we observed further increase in strain △cyoA△adhE△nuoA△ndh△pta△dld, leading to 202 mg/g dry cell weight of total fatty acids, ~250% of that in the wild-type strain. Meanwhile, we successfully introduced a triacylglycerol biosynthesis pathway into E. coli through heterologous expression of wax ester synthase/acyl-coenzyme:diacylglycerol acyltransferase (WS/DGAT) enzymes. The added pathway improved both the amount and fuel quality of the fatty acids. These new metabolic engineering strategies are providing promising directions for future investigation. PMID:24147139

  11. Myocardial imaging and metabolic studies with (17-/sup 123/I)iodoheptadecanoic acid

    SciTech Connect

    Freundlieb, C.; Hoeck, A.; Vyska, K.; Feinendegen, L.E.; Machulla, H.J.; Stoecklin, G.

    1980-11-01

    After intravenous administration of the stearic acid analogue (17-/sup 123/I)iodoheptadecanoic acid (I-123 HA), myocardial metabolism was studied in ten normal individuals, eight patients with coronary artery disease and three patients with congestive heart failure. High-quality images were obtained in sequential scintigraphy of I-123 metabolically bound in myocardial tissue. Infarcted zones as well as ischemic regions are indicated by reduced tracer uptake. Iodine-123 in the blood pool and interstitial space consists mainly of radioiodide that is liberated by fatty-acid metabolism and was corrected for. Using the proposed correction not only are the images improved but the uptake and elimination of the I-123 in the myocardial cells can be followed. The average disappearance half-time of I-123 HA from the myocardium of normal persons was 24 +- 4.7 min. In patients with coronary artery disease significant differences between myocardial regions were observed.

  12. Incorporation and metabolism of dietary trans isomers of linolenic acid alter the fatty acid profile of rat tissues.

    PubMed

    Loï, C; Chardigny, J M; Almanza, S; Leclere, L; Ginies, C; Sébédio, J L

    2000-10-01

    To study the influence on lipid metabolism and platelet aggregation of the fatty acid isomerization that occurs during heat treatment, weanling rats were fed for 8 wk a diet enriched with 5% isomerized (experimental group) or normal (control group) canola oil. Geometrical isomers of alpha-linolenic acid representing 0.2 g/100 g of the experimental diet were incorporated into liver, platelets, aorta and heart, at the expense of their cis homologue and of 18:2(n-6). The major isomer, 9c,12c,15t-18:3, was also metabolized to 5c,8c,11c,14c,17t-20:5 and to an unknown compound, found in liver, platelets and aorta, which has been identified tentatively as 7c, 10c,13c,16c,19t-22:5. The greater 20:4(n-6)/18:2(n-6) ratio in the liver, platelets and heart of the experimental group than the control group indicated an enhancement of desaturation activities. This induced a higher content of long-chain (n-6) fatty acids in the experimental group. Platelet aggregation tended to be slightly higher (P: = 0.065) in the experimental group. We conclude that 0.2 g of trans isomers of alpha-linolenic acid per 100 g of diet was sufficient to be incorporated and metabolized, thus altering the fatty acid profile of rat tissues.

  13. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

    PubMed Central

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve

  14. 1H NMR-based metabolic profiling reveals the effects of fluoxetine on lipid and amino acid metabolism in astrocytes.

    PubMed

    Bai, Shunjie; Zhou, Chanjuan; Cheng, Pengfei; Fu, Yuying; Fang, Liang; Huang, Wen; Yu, Jia; Shao, Weihua; Wang, Xinfa; Liu, Meiling; Zhou, Jingjing; Xie, Peng

    2015-04-15

    Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR)-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte's lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.

  15. Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition

    PubMed Central

    Ohminami, Hirokazu; Amo, Kikuko; Taketani, Yutaka; Sato, Kazusa; Fukaya, Makiko; Uebanso, Takashi; Arai, Hidekazu; Koganei, Megumi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Takeda, Eiji

    2014-01-01

    A dietary combination of sucrose and linoleic acid strongly contributes to the development of metabolic disorders in Zucker fatty rats. However, the underlying mechanisms of the metabolic disorders are poorly understood. We hypothesized that the metabolic disorders were triggered at a stage earlier than the 8 weeks we had previously reported. In this study, we investigated early molecular events induced by the sucrose and linoleic acid diet in Zucker fatty rats by comparison with other combinations of carbohydrate (sucrose or palatinose) and fat (linoleic acid or oleic acid). Skeletal muscle arachidonic acid levels were significantly increased in the sucrose and linoleic acid group compared to the other dietary groups at 4 weeks, while there were no obvious differences in the metabolic phenotype between the groups. Expression of genes related to arachidonic acid synthesis was induced in skeletal muscle but not in liver and adipose tissue in sucrose and linoleic acid group rats. In addition, the sucrose and linoleic acid group exhibited a rapid induction in endoplasmic reticulum stress and abnormal lipid metabolism in skeletal muscle. We concluded that the dietary combination of sucrose and linoleic acid primarily induces metabolic disorders in skeletal muscle through increases in arachidonic acid and endoplasmic reticulum stress, in advance of systemic metabolic disorders. PMID:25147427

  16. Metabolic Inflexibility with Obesity and the Effects of Fenofibrate on Skeletal Muscle Fatty Acid Oxidation.

    PubMed

    Boyle, Kristen E; Friedman, Jacob E; Janssen, Rachel C; Underkofler, Chantal; Houmard, Joseph A; Rasouli, Neda

    2017-01-01

    This study was designed to investigate mechanisms of lipid metabolic inflexibility in human obesity and the ability of fenofibrate (FENO) to increase skeletal muscle fatty acid oxidation (FAO) in primary human skeletal muscle cell cultures (HSkMC) exhibiting metabolic inflexibility. HSkMC from 10 lean and 10 obese, insulin resistant subjects were treated with excess fatty acid for 24 h (24hFA) to gauge lipid-related metabolic flexibility. Metabolically inflexible HSkMC from obese individuals were then treated with 24hFA in combination with FENO to determine effectiveness for increasing FAO. Mitochondrial enzyme activity and FAO were measured in skeletal muscle from subjects with prediabetes (n=11) before and after 10 weeks of fenofibrate in vivo. 24hFA increased FAO to a greater extent in HSkMC from lean versus obese subjects (+49% vs. +9%, for lean vs. obese, respectively; p<0.05) indicating metabolic inflexibility with obesity. Metabolic inflexibility was not observed for measures of cellular respiration in permeabilized cells using carbohydrate substrate. Fenofibrate co-incubation with 24hFA, increased FAO in a subset of HSkMC from metabolically inflexible, obese subjects (p<0.05), which was eliminated by PPARα antagonist. In vivo, fenofibrate treatment increased skeletal muscle FAO in a subset of subjects with prediabetes but did not affect gene transcription or mitochondrial enzyme activity. Lipid metabolic inflexibility observed in HSkMC from obese subjects is not due to differences in electron transport flux, but rather upstream decrements in lipid metabolism. Fenofibrate increases the capacity for FAO in human skeletal muscle cells, though its role in skeletal muscle metabolism in vivo remains unclear.

  17. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    PubMed

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild-type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed.

  18. Metabolic engineering of Escherichia coli for biotechnological production of high-value organic acids and alcohols.

    PubMed

    Yu, Chao; Cao, Yujin; Zou, Huibin; Xian, Mo

    2011-02-01

    Confronted with the gradual and inescapable exhaustion of the earth's fossil energy resources, the bio-based process to produce platform chemicals from renewable carbohydrates is attracting growing interest. Escherichia coli has been chosen as a workhouse for the production of many valuable chemicals due to its clear genetic background, convenient to be genetically modified and good growth properties with low nutrient requirements. Rational strain development of E. coli achieved by metabolic engineering strategies has provided new processes for efficiently biotechnological production of various high-value chemical building blocks. Compared to previous reviews, this review focuses on recent advances in metabolic engineering of the industrial model bacteria E. coli that lead to efficient recombinant biocatalysts for the production of high-value organic acids like succinic acid, lactic acid, 3-hydroxypropanoic acid and glucaric acid as well as alcohols like 1,3-propanediol, xylitol, mannitol, and glycerol with the discussion of the future research in this area. Besides, this review also discusses several platform chemicals, including fumaric acid, aspartic acid, glutamic acid, sorbitol, itaconic acid, and 2,5-furan dicarboxylic acid, which have not been produced by E. coli until now.

  19. White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways

    PubMed Central

    Barquissau, V.; Beuzelin, D.; Pisani, D.F.; Beranger, G.E.; Mairal, A.; Montagner, A.; Roussel, B.; Tavernier, G.; Marques, M.-A.; Moro, C.; Guillou, H.; Amri, E.-Z.; Langin, D.

    2016-01-01

    in PPARα-null mice displaying an impaired britening response. Conclusions Conversion of human white fat cells into brite adipocytes results in a major metabolic reprogramming inducing fatty acid anabolic and catabolic pathways. PDK4 redirects glucose from oxidation towards triglyceride synthesis and favors the use of fatty acids as energy source for uncoupling mitochondria. PMID:27110487

  20. Citric acid ingestion: a life-threatening cause of metabolic acidosis.

    PubMed

    DeMars, C S; Hollister, K; Tomassoni, A; Himmelfarb, J; Halperin, M L

    2001-11-01

    We present a case that illustrates the acute (<6 hours) metabolic and hemodynamic effects of the ingestion of a massive oral citric acid load. The principal findings included metabolic acidosis accompanied by an increase in the plasma anion gap that was not caused by L -lactic acidosis, hyperkalemia, and the abrupt onset of hypotension. A unique feature was a dramatic clinical improvement when ionized calcium was infused. The case illustrates the importance of considering the properties of the conjugate base (anion) of the added acid because, in this instance, the citrate anion had a unique and life-threatening consequence (lower ionized calcium level) that was rapidly reversible.

  1. Metabolic engineering of Escherichia coli for the production of fumaric acid.

    PubMed

    Song, Chan Woo; Kim, Dong In; Choi, Sol; Jang, Jae Won; Lee, Sang Yup

    2013-07-01

    Fumaric acid is a naturally occurring organic acid that is an intermediate of the tricarboxylic acid cycle. Fungal species belonging to Rhizopus have traditionally been employed for the production of fumaric acid. In this study, Escherichia coli was metabolically engineered for the production of fumaric acid under aerobic condition. For the aerobic production of fumaric acid, the iclR gene was deleted to redirect the carbon flux through the glyoxylate shunt. In addition, the fumA, fumB, and fumC genes were also deleted to enhance fumaric acid formation. The resulting strain was able to produce 1.45 g/L of fumaric acid from 15 g/L of glucose in flask culture. Based on in silico flux response analysis, this base strain was further engineered by plasmid-based overexpression of the native ppc gene, encoding phosphoenolpyruvate carboxylase (PPC), from the strong tac promoter, which resulted in the production of 4.09 g/L of fumaric acid. Additionally, the arcA and ptsG genes were deleted to reinforce the oxidative TCA cycle flux, and the aspA gene was deleted to block the conversion of fumaric acid into L-aspartic acid. Since it is desirable to avoid the use of inducer, the lacI gene was also deleted. To increase glucose uptake rate and fumaric acid productivity, the native promoter of the galP gene was replaced with the strong trc promoter. Fed-batch culture of the final strain CWF812 allowed production of 28.2 g/L fumaric acid in 63 h with the overall yield and productivity of 0.389 g fumaric acid/g glucose and 0.448 g/L/h, respectively. This study demonstrates the possibility for the efficient production of fumaric acid by metabolically engineered E. coli.

  2. Anaerobic organic acid metabolism of Candida zemplinina in comparison with Saccharomyces wine yeasts.

    PubMed

    Magyar, Ildikó; Nyitrai-Sárdy, Diána; Leskó, Annamária; Pomázi, Andrea; Kállay, Miklós

    2014-05-16

    Organic acid production under oxygen-limited conditions has been thoroughly studied in the Saccharomyces species, but practically never investigated in Candida zemplinina, which seems to be an acidogenic species under oxidative laboratory conditions. In this study, several strains of C. zemplinina were tested for organic acid metabolism, in comparison with Saccharomyces cerevisiae, Saccharomyces uvarum and Candida stellata, under fermentative conditions. Only C. stellata produced significantly higher acidity in simple minimal media (SM) with low sugar content and two different nitrogen sources (ammonia or glutamic acid) at low level. However, the acid profile differed largely between the Saccharomyces and Candida species and showed inverse types of N-dependence in some cases. Succinic acid production was strongly enhanced on glutamic acid in Saccharomyces species, but not in Candida species. 2-oxoglutarate production was strongly supported on ammonium nitrogen in Candida species, but remained low in Saccharomyces. Candida species, C. stellata in particular, produced more pyruvic acid regardless of N-sources. From the results, we concluded that the anaerobic organic acid metabolisms of C. zemplinina and C. stellata are different from each other and also from that of the Saccharomyces species. In the formation of succinic acid, the oxidative pathway from glutamic acid seems to play little or no role in C. zemplinina. The reductive branch of the TCA cycle, however, produces acidic intermediates (malic, fumaric, and succinic acid) in a level comparable with the production of the Saccharomyces species. An unidentified organic acid, which was produced on glutamic acid only by the Candida species, needs further investigation.

  3. A model of in vitro UDP-glucuronosyltransferase inhibition by bile acids predicts possible metabolic disorders[S

    PubMed Central

    Fang, Zhong-Ze; He, Rong-Rong; Cao, Yun-Feng; Tanaka, Naoki; Jiang, Changtao; Krausz, Kristopher W.; Qi, Yunpeng; Dong, Pei-Pei; Ai, Chun-Zhi; Sun, Xiao-Yu; Hong, Mo; Ge, Guang-Bo; Gonzalez, Frank J.; Ma, Xiao-Chi; Sun, Hong-Zhi

    2013-01-01

    Increased levels of bile acids (BAs) due to the various hepatic diseases could interfere with the metabolism of xenobiotics, such as drugs, and endobiotics including steroid hormones. UDP-glucuronosyltransferases (UGTs) are involved in the conjugation and elimination of many xenobiotics and endogenous compounds. The present study sought to investigate the potential for inhibition of UGT enzymes by BAs. The results showed that taurolithocholic acid (TLCA) exhibited the strongest inhibition toward UGTs, followed by lithocholic acid. Structure-UGT inhibition relationships of BAs were examined and in vitro-in vivo extrapolation performed by using in vitro inhibition kinetic parameters (Ki) in combination with calculated in vivo levels of TLCA. Substitution of a hydrogen with a hydroxyl group in the R1, R3, R4, R5 sites of BAs significantly weakens their inhibition ability toward most UGTs. The in vivo inhibition by TLCA toward UGT forms was determined with following orders of potency: UGT1A4 > UGT2B7 > UGT1A3 > UGT1A1 ∼ UGT1A7 ∼ UGT1A10 ∼ UGT2B15. In conclusion, these studies suggest that disrupted homeostasis of BAs, notably taurolithocholic acid, found in various diseases such as cholestasis, could lead to altered metabolism of xenobiotics and endobiotics through inhibition of UGT enzymes. PMID:24115227

  4. Hydroxycarboxylic acid receptors are essential for breast cancer cells to control their lipid/fatty acid metabolism.

    PubMed

    Stäubert, Claudia; Broom, Oliver Jay; Nordström, Anders

    2015-08-14

    Cancer cells exhibit characteristic changes in their metabolism with efforts being made to address them therapeutically. However, targeting metabolic enzymes as such is a major challenge due to their essentiality for normal proliferating cells. The most successful pharmaceutical targets are G protein-coupled receptors (GPCRs), with more than 40% of all currently available drugs acting through them.We show that, a family of metabolite-sensing GPCRs, the Hydroxycarboxylic acid receptor family (HCAs), is crucial for breast cancer cells to control their metabolism and proliferation.We found HCA1 and HCA3 mRNA expression were significantly increased in breast cancer patient samples and detectable in primary human breast cancer patient cells. Furthermore, siRNA mediated knock-down of HCA3 induced considerable breast cancer cell death as did knock-down of HCA1, although to a lesser extent. Liquid Chromatography Mass Spectrometry based analyses of breast cancer cell medium revealed a role for HCA3 in controlling intracellular lipid/fatty acid metabolism. The presence of etomoxir or perhexiline, both inhibitors of fatty acid β-oxidation rescues breast cancer cells with knocked-down HCA3 from cell death.Our data encourages the development of drugs acting on cancer-specific metabolite-sensing GPCRs as novel anti-proliferative agents for cancer therapy.

  5. Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes

    PubMed Central

    Heimann, Emilia; Nyman, Margareta; Pålbrink, Ann-Ki; Lindkvist-Petersson, Karin; Degerman, Eva

    2016-01-01

    ABSTRACT Short-chain fatty acids (SCFAs), e.g. acetic acid, propionic acid and butyric acid, generated through colonic fermentation of dietary fibers, have been shown to reach the systemic circulation at micromolar concentrations. Moreover, SCFAs have been conferred anti-obesity properties in both animal models and human subjects. Branched SCFAs (BSCFAs), e.g., isobutyric and isovaleric acid, are generated by fermentation of branched amino acids, generated from undigested protein reaching colon. However, BSCFAs have been sparsely investigated when referring to effects on energy metabolism. Here we primarily investigate the effects of isobutyric acid and isovaleric acid on glucose and lipid metabolism in primary rat and human adipocytes. BSCFAs inhibited both cAMP-mediated lipolysis and insulin-stimulated de novo lipogenesis at 10 mM, whereas isobutyric acid potentiated insulin-stimulated glucose uptake by all concentrations (1, 3 and 10 mM) in rat adipocytes. For human adipocytes, only SCFAs inhibited lipolysis at 10 mM. In both in vitro models, BSCFAs and SCFAs reduced phosphorylation of hormone sensitive lipase, a rate limiting enzyme in lipolysis. In addition, BSCFAs and SCFAs, in contrast to insulin, inhibited lipolysis in the presence of wortmannin, a phosphatidylinositide 3-kinase inhibitor and OPC3911, a phosphodiesterase 3 inhibitor in rat adipocytes. Furthermore, BSCFAs and SCFAs reduced insulin-mediated phosphorylation of protein kinase B. To conclude, BSCFAs have effects on adipocyte lipid and glucose metabolism that can contribute to improved insulin sensitivity in individuals with disturbed metabolism. PMID:27994949

  6. Toxic synergism between quinolinic acid and organic acids accumulating in glutaric acidemia type I and in disorders of propionate metabolism in rat brain synaptosomes: Relevance for metabolic acidemias.

    PubMed

    Colín-González, A L; Paz-Loyola, A L; Serratos, I; Seminotti, B; Ribeiro, C A J; Leipnitz, G; Souza, D O; Wajner, M; Santamaría, A

    2015-11-12

    The brain of children affected by organic acidemias develop acute neurodegeneration linked to accumulation of endogenous toxic metabolites like glutaric (GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids. Excitotoxic and oxidative events are involved in the toxic patterns elicited by these organic acids, although their single actions cannot explain the extent of brain damage observed in organic acidemias. The characterization of co-adjuvant factors involved in the magnification of early toxic processes evoked by these metabolites is essential to infer their actions in the human brain. Alterations in the kynurenine pathway (KP) - a metabolic route devoted to degrade tryptophan to form NAD(+) - produce increased levels of the excitotoxic metabolite quinolinic acid (QUIN), which has been involved in neurodegenerative disorders. Herein we investigated the effects of subtoxic concentrations of GA, 3-OHGA, MMA and PA, either alone or in combination with QUIN, on early toxic endpoints in rat brain synaptosomes. To establish specific mechanisms, we pre-incubated synaptosomes with different protective agents, including the endogenous N-methyl-d-aspartate (NMDA) receptor antagonist kynurenic acid (KA), the antioxidant S-allylcysteine (SAC) and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME). While the incubation of synaptosomes with toxic metabolites at subtoxic concentrations produced no effects, their co-incubation (QUIN+GA, +3-OHGA, +MMA or +PA) decreased the mitochondrial function and increased reactive oxygen species (ROS) formation and lipid peroxidation. For all cases, this effect was partially prevented by KA and l-NAME, and completely avoided by SAC. These findings suggest that early damaging events elicited by organic acids involved in metabolic acidemias can be magnified by toxic synergism with QUIN, and this process is mostly mediated by oxidative stress, and in a lesser extent by excitotoxicity and

  7. Apparent Role of Phosphatidylcholine in the Metabolism of Petroselinic Acid in Developing Umbelliferae Endosperm.

    PubMed Central

    Cahoon, E. B.; Ohlrogge, J. B.

    1994-01-01

    Studies were conducted to characterize the metabolism of the unusual fatty acid petroselinic acid (18:1cis[delta]6) in developing endosperm of the Umbelliferae species coriander (Coriandrum sativum L.) and carrot (Daucus carota L.). Analyses of fatty acid compositions of glycerolipids of these tissues revealed a dissimilar distribution of petroselinic acid in triacylglycerols (TAG) and the major polar lipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Petroselinic acid comprised 70 to 75 mol% of the fatty acids of TAG but only 9 to 20 mol% of the fatty acids of PC and PE. Although such data appeared to suggest that petroselinic acid is at least partially excluded from polar lipids, results of [1-14C]acetate radiolabeling experiments gave a much different picture of the metabolism of this fatty acid. In time-course labeling of carrot endosperm, [1-14C]acetate was rapidly incorporated into PC in high levels. Through 30 min, radiolabel was most concentrated in PC, and of this, 80 to 85% was in the form of petroselinic acid. One explanation for the large disparity in amounts of petroselinic acid in PC as determined by fatty acid mass analyses and 14C radiolabeling is that turnover of these lipids or the fatty acids of these lipids results in relatively low accumulation of petroselinic acid mass. Consistent with this, the kinetics of [1-14C]acetate time-course labeling of carrot endosperm and "pulse-chase" labeling of coriander endosperm suggested a possible flux of fatty acids from PC into TAG. In time-course experiments, radiolabel initially entered PC at the highest rates but accumulated in TAG at later time points. Similarly, in pulse-chase studies, losses in absolute amounts of radioactivity from PC were accompanied by significant increases of radiolabel in TAG. In addition, stereospecific analyses of unlabeled and [1-14C]acetate-labeled PC of coriander endosperm indicated that petroselinic acid can be readily incorporated into both the sn-1 and sn

  8. Hydroxyoctadecadienoic acids: Oxidised derivatives of linoleic acid and their role in inflammation associated with metabolic syndrome and cancer.

    PubMed

    Vangaveti, Venkat N; Jansen, Holger; Kennedy, Richard Lee; Malabu, Usman H

    2016-08-15

    Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo

  9. Metabolic fate of [14C]-labeled meal protein amino acids in Aedes aegypti mosquitoes.

    PubMed

    Zhou, Guoli; Flowers, Matthew; Friedrich, Kenneth; Horton, James; Pennington, James; Wells, Michael A

    2004-04-01

    We developed a method to follow the metabolic fate of [(14)C]-labeled Euglena gracilis protein amino acids in Aedes aegypti mosquitoes under three different adult nutritional regimes. Quantitative analysis of blood meal protein amino acid metabolism showed that most of the carbon of the amino acids was either oxidized to CO(2) or excreted as waste. Under the three different adult nutritional regimes, no significant differences in the metabolism of amino acids were found, which indicated that the female A. aegypti mosquitoes possess a substantial capacity of maintaining metabolic homeostasis during a gonotrophic cycle. The amount of maternal glycogen and lipid after egg laying were significantly lower in the mosquitoes that underwent a partial starvation before a blood meal and/or starvation after the blood meal. The content of egg lipid or protein or the number of eggs laid did not show a significant difference among the three different regimes, which indicates that stable fecundity of A. aegypti under the partial starvation before a blood meal and/or starvation after the blood meal seemed to result from a trade-off between current fecundity and future survival after the eggs laid. The methods described in this paper can be applied to a wide range of questions about the effects of environmental conditions on the utilization of blood meal amino acids.

  10. Metabolic engineering of yeast to produce fatty acid-derived biofuels: bottlenecks and solutions

    PubMed Central

    Sheng, Jiayuan; Feng, Xueyang

    2015-01-01

    Fatty acid-derived biofuels can be a better solution than bioethanol to replace petroleum fuel, since they have similar energy content and combustion properties as current transportation fuels. The environmentally friendly microbial fermentation process has been used to synthesize advanced biofuels from renewable feedstock. Due to their robustness as well as the high tolerance to fermentation inhibitors and phage contamination, yeast strains such as Saccharomyces cerevisiae and Yarrowia lipolytica have attracted tremendous attention in recent studies regarding the production of fatty acid-derived biofuels, including fatty acids, fatty acid ethyl esters, fatty alcohols, and fatty alkanes. However, the native yeast strains cannot produce fatty acids and fatty acid-derived biofuels in large quantities. To this end, we have summarized recent publications in this review on metabolic engineering of yeast strains to improve the production of fatty acid-derived biofuels, identified the bottlenecks that limit the productivity of biofuels, and categorized the appropriate approaches to overcome these obstacles. PMID:26106371

  11. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    PubMed

    Hatazawa, Yukino; Tadaishi, Miki; Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

    2014-01-01

    Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  12. Distinct effects of sorbic acid and acetic acid on the electrophysiology and metabolism of Bacillus subtilis.

    PubMed

    van Beilen, J W A; Teixeira de Mattos, M J; Hellingwerf, K J; Brul, S

    2014-10-01

    Sorbic acid and acetic acid are among the weak organic acid preservatives most commonly used to improve the microbiological stability of foods. They have similar pKa values, but sorbic acid is a far more potent preservative. Weak organic acids are most effective at low pH. Under these circumstances, they are assumed to diffuse across the membrane as neutral undissociated acids. We show here that the level of initial intracellular acidification depends on the concentration of undissociated acid and less on the nature of the acid. Recovery of the internal pH depends on the presence of an energy source, but acidification of the cytosol causes a decrease in glucose flux. Furthermore, sorbic acid is a more potent uncoupler of the membrane potential than acetic acid. Together these effects may also slow the rate of ATP synthesis significantly and may thus (partially) explain sorbic acid's effectiveness.

  13. Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

    PubMed Central

    Ferreri, Carla; Masi, Annalisa; Sansone, Anna; Giacometti, Giorgia; Larocca, Anna Vita; Menounou, Georgia; Scanferlato, Roberta; Tortorella, Silvia; Rota, Domenico; Conti, Marco; Deplano, Simone; Louka, Maria; Maranini, Anna Rosaria; Salati, Arianna; Sunda, Valentina; Chatgilialoglu, Chryssostomos

    2016-01-01

    Fatty acids, as structural components of membranes and inflammation/anti-inflammatory mediators, have well-known protective and regulatory effects. They are studied as biomarkers of pathological conditions, as well as saturated and unsaturated hydrophobic moieties in membrane phospholipids that contribute to homeostasis and physiological functions. Lifestyle, nutrition, metabolism and stress—with an excess of radical and oxidative processes—cause fatty acid changes that are examined in the human body using blood lipids. Fatty acid-based membrane lipidomics represents a powerful diagnostic tool for assessing the quantity and quality of fatty acid constituents and also for the follow-up of the membrane fatty acid remodeling that is associated with different physiological and pathological conditions. This review focuses on fatty acid biomarkers with two examples of recent lipidomic research and health applications: (i) monounsaturated fatty acids and the analytical challenge offered by hexadecenoic fatty acids (C16:1); and (ii) the cohort of 10 fatty acids in phospholipids of red blood cell membranes and its connections to metabolic and nutritional status in healthy and diseased subjects. PMID:28025506

  14. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    SciTech Connect

    Hingorani, V.; Brecher, P.

    1987-05-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

  15. New insights into the regulation of plant immunity by amino acid metabolic pathways.

    PubMed

    Zeier, Jürgen

    2013-12-01

    Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity.

  16. Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats

    SciTech Connect

    Zordoky, Beshay N.M.; Anwar-Mohamed, Anwar; Aboutabl, Mona E.

    2010-01-01

    Doxorubicin (DOX) is a potent anti-neoplastic antibiotic used to treat a variety of malignancies; however, its use is limited by dose-dependent cardiotoxicity. Moreover, there is a strong correlation between cytochrome P450 (CYP)-mediated arachidonic acid metabolites and the pathogenesis of many cardiovascular diseases. Therefore, in the current study, we have investigated the effect of acute DOX toxicity on the expression of several CYP enzymes and their associated arachidonic acid metabolites in the heart of male Sprague-Dawley rats. Acute DOX toxicity was induced by a single intraperitoneal injection of 15 mg/kg of the drug. Our results showed that DOX treatment for 24 h caused a significant induction of CYP1A1, CYP1B1, CYP2C11, CYP2J3, CYP4A1, CYP4A3, CYP4F1, CYP4F4, and EPHX2 gene expression in the heart of DOX-treated rats as compared to the control. Similarly, there was a significant induction of CYP1A1, CYP1B1, CYP2C11, CYP2J3, CYP4A, and sEH proteins after 24 h of DOX administration. In the heart microsomes, acute DOX toxicity significantly increased the formation of 20-HETE which is consistent with the induction of the major CYP omega-hydroxylases: CYP4A1, CYP4A3, CYP4F1, and CYP4F4. On the other hand, the formation of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) was significantly reduced, whereas the formation of their corresponding dihydroxyeicosatrienoic acids was significantly increased. The decrease in the cardioprotective EETs can be attributed to the increase of sEH activity parallel to the induction of the EPHX2 gene expression in the heart of DOX-treated rats. In conclusion, acute DOX toxicity alters the expression of several CYP and sEH enzymes with a consequent alteration in arachidonic acid metabolism. These results may represent a novel mechanism by which this drug causes progressive cardiotoxicity.

  17. Metabolic regulation of amino acid uptake in marine waters

    SciTech Connect

    Kirchman, D.L.; Hodson, R.E.

    1986-03-01

    To determine the relationships among the processes of uptake, intracellular pool formation, and incorporation of amino acids into protein, the authors measured the uptake of dipeptides and free amino acids by bacterial assemblages in estuarine and coastal waters of the southeast US. The dipeptide phenylalanyl-phenylalanine (phe-phe) lowered V/sub max/ of phenylalanine uptake when the turnover rate of phenylalanine was relatively high. When the turnover rate was relatively low, phe-phe either had no effect or increased V/sub max/ of phenylalanine uptake. An analytical model was developed and tested to measure the turnover time of the intracellular pool of phenylalanine. The results suggested that the size of the intracellular pool is regulated, which precludes high assimilation rates of both phenylalanine and phe-phe. In waters with relatively low phenylalanine turnover rates, bacterial assemblages appear to have a greater capacity to assimilate phenylalanine and phe-phe simultaneously. Marine bacterial assemblages do not substantially increase the apparent respiration of amino acids when concentrations increase. The authors conclude that sustained increases in uptake rates and mineralization by marine bacterial assemblages in response to an increase in the concentrations of dissolved organic nitrogen is determined by the rate of protein synthesis.

  18. Arachidonic acid metabolism in glutathione-deficient macrophages.

    PubMed Central

    Rouzer, C A; Scott, W A; Griffith, O W; Hamill, A L; Cohn, Z A

    1982-01-01

    Mouse resident peritoneal macrophages were treated with the glutathione (GSH) synthesis inhibitor buthionine sulfoximine to deplete intracellular GSH. The arachidonic acid metabolites released by the GSH-depleted macrophages in response to a zymosan challenge were analyzed by HPLC. Buthionine sulfoximine treatment resulted in inhibition of both prostaglandin E2 and leukotriene C synthesis that was directly related to the degree of GSH depletion. Macrophages in which GSH levels were reduced to 3% of normal exhibited reductions to 4% and 1%, respectively, in PGE2 and LTC formation. The total quantity of cyclooxygenase metabolites secreted by GSH-deficient macrophages was identical to that of control cells as a result of increased synthesis of prostacyclin and, to a lesser extent, 12-L-hydroxy-5,8,10-heptadecatrienoic acid. Total lipoxygenase products were decreased, however; increased formation of hydroxyicosatetraenoic acids only partially compensated for the deficit in leukotriene C production. These findings extent our earlier observations on the inhibition of leukotriene C synthesis in GSH-depleted macrophages and confirm with intact cells the previously suggested role of GSH in prostaglandin E2 formation. PMID:6803245

  19. Brain energy metabolism spurns fatty acids as fuel due to their inherent mitotoxicity and potential capacity to unleash neurodegeneration.

    PubMed

    Schönfeld, Peter; Reiser, Georg

    2017-03-30

    The brain uses long-chain fatty acids (LCFAs) to a negligible extent as fuel for the mitochondrial energy generation, in contrast to other tissues that also demand high energy. Besides this generally accepted view, some studies using cultured neural cells or whole brain indicate a moderately active mitochondrial β-oxidation. Here, we corroborate the conclusion that brain mitochondria are unable to oxidize fatty acids. In contrast, the combustion of liver-derived ketone bodies by neural cells is long-known. Furthermore, new insights indicate the use of odd-numbered medium-chain fatty acids as valuable source for maintaining the level of intermediates of the citric acid cycle in brain mitochondria. Non-esterified LCFAs or their activated forms exert a large variety of harmful side-effects on mitochondria, such as enhancing the mitochondrial ROS generation in distinct steps of the β-oxidation and therefore potentially increasing oxidative stress. Hence, the question arises: Why do in brain energy metabolism mitochondria selectively spurn LCFAs as energy source? The most likely answer are the relatively higher content of peroxidation-sensitive polyunsaturated fatty acids and, the low antioxidative defense in brain tissue. There are two remarkable peroxisomal defects, one relating to α-oxidation of phytanic acid and the other to uptake of very long-chain fatty acids (VLCFAs) which lead to pathologically high tissue levels of such fatty acids. Both, the accumulation of phytanic acid and that of VLCFAs give an enlightening insight into harmful activities of fatty acids on neural cells, which possibly explain why evolution has prevented brain mitochondria from the equipment of with significant β-oxidation enzymatic capacity.

  20. Metabolic pathways and fermentative production of L-aspartate family amino acids.

    PubMed

    Park, Jin Hwan; Lee, Sang Yup

    2010-06-01

    The L-aspartate family amino acids (AFAAs), L-threonine, L-lysine, L-methionine and L-isoleucine have recently been of much interest due to their wide spectrum of applications including food additives, components of cosmetics and therapeutic agents, and animal feed additives. Among them, L-threonine, L-lysine and L-methionine are three major amino acids produced currently throughout the world. Recent advances in systems metabolic engineering, which combine various high-throughput omics technologies and computational analysis, are now facilitating development of microbial strains efficiently producing AFAAs. Thus, a thorough understanding of the metabolic and regulatory mechanisms of the biosynthesis of these amino acids is urgently needed for designing system-wide metabolic engineering strategies. Here we review the details of AFAA biosynthetic pathways, regulations involved, and export and transport systems, and provide general strategies for successful metabolic engineering along with relevant examples. Finally, perspectives of systems metabolic engineering for developing AFAA overproducers are suggested with selected exemplary studies.

  1. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    SciTech Connect

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  2. Reappraisal of the 20th-century version of amino acid metabolism.

    PubMed

    Katagiri, Masayuki; Nakamura, Masahiko

    2003-12-05

    In this article, we advocate the radical revision of the 20th-century version of amino acid metabolism as follows. (1) Classic studies on the incorporation of [15N]ammonia into glutamate, once considered to be an epoch-making event, are not distinctive proof of the ability of animals to utilize ammonia for the synthesis of alpha-amino nitrogen. (2) Mammalian glutamate dehydrogenase has been implicated to function as a glutamate-synthesizing enzyme albeit lack of convincing proof. This enzyme, in combination with aminotransferases, is now known to play an exclusive role in the metabolic removal of amino nitrogen and energy production from excess amino acids. (3) Dr. William C Rose's "nutritionally nonessential amino acids" are, of course, essential in cellular metabolism; the nutritional nonessentiality is related to their carbon skeletons, many of which are intermediates of glycolysis or the TCA cycle. Obviously, the prime importance of amino acid nutrition should be the means of obtaining amino nitrogen. (4) Because there is no evidence of the presence of any glutamate-synthesizing enzymes in mammalian tissues, animals must depend on plants and microorganisms for preformed alpha-amino nitrogen. This is analogous to the case of carbohydrates. (5) In contrast, individual essential amino acids, similar to vitamins and essential fatty acids, should be considered important nutrients that must be included regularly in sufficient amounts in the diet.

  3. Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum.

    PubMed

    Amador-Noguez, Daniel; Feng, Xiao-Jiang; Fan, Jing; Roquet, Nathaniel; Rabitz, Herschel; Rabinowitz, Joshua D

    2010-09-01

    Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways of Clostridium acetobutylicum, a soil bacterium whose major fermentation products include the biofuels butanol and hydrogen. While genome annotation suggests the absence of most tricarboxylic acid (TCA) cycle enzymes, our results demonstrate that this bacterium has a complete, albeit bifurcated, TCA cycle; oxaloacetate flows to succinate both through citrate/alpha-ketoglutarate and via malate/fumarate. Our investigations also yielded insights into the pathways utilized for glucose catabolism and amino acid biosynthesis and revealed that the organism's one-carbon metabolism is distinct from that of model microbes, involving reversible pyruvate decarboxylation and the use of pyruvate as the one-carbon donor for biosynthetic reactions. This study represents the first in vivo characterization of the TCA cycle and central metabolism of C. acetobutylicum. Our results establish a role for the full TCA cycle in an obligatory anaerobic organism and demonstrate the importance of complementing genome annotation with isotope tracer studies for determining the metabolic pathways of diverse microbes.

  4. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism

    PubMed Central

    Yoon, Mee-Sup

    2016-01-01

    Insulin is required for maintenance of glucose homeostasis. Despite the importance of insulin sensitivity to metabolic health, the mechanisms that induce insulin resistance remain unclear. Branched-chain amino acids (BCAAs) belong to the essential amino acids, which are both direct and indirect nutrient signals. Even though BCAAs have been reported to improve metabolic health, an increased BCAA plasma level is associated with a high risk of metabolic disorder and future insulin resistance, or type 2 diabetes mellitus (T2DM). The activation of mammalian target of rapamycin complex 1 (mTORC1) by BCAAs has been suggested to cause insulin resistance. In addition, defective BCAA oxidative metabolism might occur in obesity, leading to a further accumulation of BCAAs and toxic intermediates. This review provides the current understanding of the mechanism of BCAA-induced mTORC1 activation, as well as the effect of mTOR activation on metabolic health in terms of insulin sensitivity. Furthermore, the effects of impaired BCAA metabolism will be discussed in detail. PMID:27376324

  5. Lactobacillus acidophilus NCFM affects vitamin E acetate metabolism and intestinal bile acid signature in monocolonized mice.

    PubMed

    Roager, Henrik M; Sulek, Karolina; Skov, Kasper; Frandsen, Henrik L; Smedsgaard, Jørn; Wilcks, Andrea; Skov, Thomas H; Villas-Boas, Silas G; Licht, Tine R

    2014-01-01

    Monocolonization of germ-free (GF) mice enables the study of specific bacterial species in vivo. Lactobacillus acidophilus NCFM(TM) (NCFM) is a probiotic strain; however, many of the mechanisms behind its health-promoting effect remain unknown. Here, we studied the effects of NCFM on the metabolome of jejunum, cecum, and colon of NCFM monocolonized (MC) and GF mice using liquid chromatography coupled to mass-spectrometry (LC-MS). The study adds to existing evidence that NCFM in vivo affects the bile acid signature of mice, in particular by deconjugation. Furthermore, we confirmed that carbohydrate metabolism is affected by NCFM in the mouse intestine as especially the digestion of oligosaccharides (penta- and tetrasaccharides) was increased in MC mice. Additionally, levels of α-tocopherol acetate (vitamin E acetate) were higher in the intestine of GF mice than in MC mice, suggesting that NCFM affects the vitamin E acetate metabolism. NCFM did not digest vitamin E acetate in vitro, suggesting that direct bacterial metabolism was not the cause of the altered metabolome in vivo. Taken together, our results suggest that NCFM affects intestinal carbohydrate metabolism, bile acid metabolism and vitamin E metabolism, although it remains to be investigated whether this effect is unique to NCFM.

  6. Postprandial metabolism of docosapentaenoic acid (DPA, 22:5n-3) and eicosapentaenoic acid (EPA, 20:5n-3) in humans.

    PubMed

    Linderborg, Kaisa M; Kaur, Gunveen; Miller, Eliza; Meikle, Peter J; Larsen, Amy E; Weir, Jacquelyn M; Nuora, Anu; Barlow, Christopher K; Kallio, Heikki P; Cameron-Smith, David; Sinclair, Andrew J

    2013-04-01

    The study of the metabolism of docosapentaenoic acid (DPA, 22:5n-3) in humans has been limited by the unavailability of pure DPA and the fact that DPA is found in combination with eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in natural products. In this double blind cross over study, pure DPA and EPA were incorporated in meals served to healthy female volunteers. Mass spectrometric methods were used to study the chylomicron lipidomics. Plasma chylomicronemia was significantly reduced after the meal containing DPA compared with the meal containing EPA or olive oil only. Both EPA and DPA were incorporated into chylomicron TAGs, while there was less incorporation into chylomicron phospholipids. Lipidomic analysis of the chylomicron TAGs revealed the dynamic nature of chylomicron TAGs. The main TAG species that EPA and DPA were incorporated into were EPA/18:1/18:1, DPA/18:1/16:0 and DPA/18:1/18:1. There was very limited conversion of DPA and EPA to DHA and there were no increases in EPA levels during the 5h postprandial period after the DPA meal. In conclusion, EPA and DPA showed different metabolic fates, and DPA hindered the digestion, ingestion or incorporation into chylomicrons of the olive oil present in the meal.

  7. Metabolites involved in Glycolysis and Amino Acid Metabolism are Altered in Short Children Born Small for Gestational Age

    PubMed Central

    Murray, Philip G; Butcher, Imogen; Dunn, Warwick B; Stevens, Adam; Perchard, Reena; Hanson, Daniel; Whatmore, Andrew; Westwood, Melissa; Clayton, Peter E

    2016-01-01

    Background Later life metabolic dysfunction is a well-recognised consequence of being born Small for Gestational Age (SGA). This study has applied metabolomics to identify whether there are changes in these pathways in pre-pubertal short SGA children and aimed to compare the intracellular and extracellular metabolome in fibroblasts derived from healthy children and SGA children with post-natal growth impairment. Methods Skin fibroblast cell lines were established from eight SGA children (age 1.8 -10.3 years) with failure of catch-up growth and from three healthy control children. Confluent cells were incubated in serum free media and the spent growth medium (metabolic footprint) and intracellular metabolome (metabolic fingerprint) were analysed by gas-chromatography mass spectrometry. Results 19 metabolites were significantly altered between SGA and control cell lines. The greatest fold difference (FD) was seen for alanine (fingerprint FD, SGA: control) 0.3, p=0.01 and footprint FD=0.19, p=0.01), aspartic acid (fingerprint FD=5.21, p=0.01) and cystine (footprint FD=1.66, p=0.02). Network analysis of the differentially expressed metabolites predicted inhibition of insulin and activation of ERK/AKT/PI3K signalling in SGA cells. Conclusions This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in pre-pubertal short children born SGA. PMID:27057740

  8. Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity

    PubMed Central

    Assies, J; Mocking, R J T; Lok, A; Ruhé, H G; Pouwer, F; Schene, A H

    2014-01-01

    Objective Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive responses, might underlie comorbidity between CVD and psychiatric disorders. Method We conducted a literature search and integrated data in a narrative review. Results Oxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine and antioxidant glutathione). Interestingly, corresponding alterations were reported in psychiatric disorders and CVD. Potential mechanisms through which FA and 1-C cycle metabolism may be involved in brain (neurocognition, mood regulation) and cardiovascular system functioning (inflammation, thrombosis) include membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics. Conclusion While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients. PMID:24649967

  9. Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases.

    PubMed

    Kolrep, Franziska; Hessel, Stefanie; These, Anja; Ehlers, Anke; Rein, Kathleen; Lampen, Alfonso

    2016-08-01

    The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear. The aim of our study was to detect the cellular effects in HepG2 cells exposed to OA in the presence of recombinant CYP enzymes of both rat and human for the investigation of species differences. The results should be set in correlation with a CYP-specific metabolite pattern. Comparative metabolite profiles of OA after incubation in rat and human recombinant CYP enzymes were established by using LC-MS/MS technique. Results demonstrated that metabolism of OA to oxygenated metabolites correlates with detoxification which was mainly catalyzed by human CYP3A4 and CYP3A5. Detoxification by rat Cyp3a1 was lower compared to human CYP3A enzymes and activation of OA by Cyp3a2 was observed, coincident with minor overall conversion capacity of OA. By contrast human and rat CYP1A2 seem to activate OA into cytotoxic intermediates. In conclusion, different mechanisms of OA metabolism may occur in the liver. At low OA doses, the human liver is likely well protected against cytotoxic OA, but for high shellfish consumers a potential risk cannot be excluded.

  10. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    PubMed Central

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-01-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress. PMID:26552588

  11. Sulfur alleviates arsenic toxicity by reducing its accumulation and modulating proteome, amino acids and thiol metabolism in rice leaves

    NASA Astrophysics Data System (ADS)

    Dixit, Garima; Singh, Amit Pal; Kumar, Amit; Dwivedi, Sanjay; Deeba, Farah; Kumar, Smita; Suman, Shankar; Adhikari, Bijan; Shukla, Yogeshwar; Trivedi, Prabodh Kumar; Pandey, Vivek; Tripathi, Rudra Deo

    2015-11-01

    Arsenic (As) contamination of water is a global concern and rice consumption is the biggest dietary exposure to human posing carcinogenic risks, predominantly in Asia. Sulfur (S) is involved in di-sulfide linkage in many proteins and plays crucial role in As detoxification. Present study explores role of variable S supply on rice leaf proteome, its inclination towards amino acids (AA) profile and non protein thiols under arsenite exposure. Analysis of 282 detected proteins on 2-DE gel revealed 113 differentially expressed proteins, out of which 80 were identified by MALDI-TOF-TOF. The identified proteins were mostly involved in glycolysis, TCA cycle, AA biosynthesis, photosynthesis, protein metabolism, stress and energy metabolism. Among these, glycolytic enzymes play a major role in AA biosynthesis that leads to change in AAs profiling. Proteins of glycolytic pathway, photosynthesis and energy metabolism were also validated by western blot analysis. Conclusively S supplementation reduced the As accumulation in shoot positively skewed thiol metabolism and glycolysis towards AA accumulation under AsIII stress.

  12. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera)

    PubMed Central

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-01-01

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis. PMID:27455877

  13. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera).

    PubMed

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-07-26

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis.

  14. CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Disruption of the circadian system may be causal for manifestations of Metabolic Syndrome (MetS). Objective: To study the associations of five CLOCK polymorphisms with MetS features considering fatty acid (FA) composition, from dietary and red-blood-cells (RBC) membrane sources. Design: ...

  15. Regulation of the expression of key genes involved in HDL metabolism by unsaturated fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of this study was to determine the effects, and possible mechanisms of action, of unsaturated fatty acids on the expression of genes involved in HDL metabolism in HepG2 cells. The mRNA concentration of target genes was assessed by real time PCR. Protein concentrations were determined by wes...

  16. UPTAKE AND METABOLISM OF ALL-TRANS RETINOIC ACID BY THREE NATIVE NORTH AMERICAN RANIDS

    EPA Science Inventory

    Retinoids, which are Vvitamin A derivatives, are important signaling molecules that regulate processes critical for development in all vertebrates. The objective of our study was to examine uptake and metabolism of the model retinoid, all-trans retinoic acid (all-trans RA), by th...

  17. Physiological and metabolic effects of 5-aminolevulinic acid for mitigating salinity stress in creeping bentgrass.

    PubMed

    Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

    2014-01-01

    The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L-1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense.

  18. Physiological and Metabolic Effects of 5-Aminolevulinic Acid for Mitigating Salinity Stress in Creeping Bentgrass

    PubMed Central

    Yang, Zhimin; Chang, Zuoliang; Sun, Lihong; Yu, Jingjin; Huang, Bingru

    2014-01-01

    The objectives of this study were to determine whether foliar application of a chlorophyll precursor, 5-aminolevulinic acid (ALA), could mitigate salinity stress damages in perennial grass species by regulating photosynthetic activities, ion content, antioxidant metabolism, or metabolite accumulation. A salinity-sensitive perennial grass species, creeping bentgrass (Agrostis stolonifera), was irrigated daily with 200 mM NaCl for 28 d, which were foliar sprayed with water or ALA (0.5 mg L−1) weekly during the experiment in growth chamber. Foliar application of ALA was effective in mitigating physiological damage resulting from salinity stress, as manifested by increased turf quality, shoot growth rate, leaf relative water content, chlorophyll content, net photosynthetic rate, stomatal conductance and transpiration rate. Foliar application of ALA also alleviated membrane damages, as shown by lower membrane electrolyte leakage and lipid peroxidation, which was associated with increases in the activities of antioxidant enzymes. Leaf content of Na+ was reduced and the ratio of K+/Na+ was increased with ALA application under salinity stress. The positive effects of ALA for salinity tolerance were also associated with the accumulation of organic acids (α-ketoglutaric acid, succinic acid, and malic acid), amino acids (alanine, 5-oxoproline, aspartic acid, and γ -aminobutyric acid), and sugars (glucose, fructose, galactose, lyxose, allose, xylose, sucrose, and maltose). ALA-mitigation of physiological damages by salinity could be due to suppression of Na+ accumulation and enhanced physiological and metabolic activities related to photosynthesis, respiration, osmotic regulation, and antioxidant defense. PMID:25551443

  19. Nalidixic Acid and Macromolecular Metabolism in Tetrahymena pyriformis: Effects on Protein Synthesis

    PubMed Central

    de Castro, J. F.; Carvalho, J. F. O.; Moussatché, N.; de Castro, F. T.

    1975-01-01

    A study on the effect of nalidixic acid on macromolecular metabolism, particularly of protein, in Tetrahymena pyriformis was performed. It was shown that the compound is a potent inhibitor of deoxyribonucleic acid, ribonucleic acid, and protein synthesis for this organism. A conspicuous breakdown of polysomes, accompanied by the accumulation of 80S ribosomes, occurred in cells incubated for 10 min with the drug; polysome formation was prevented. The accumulating 80S particles were shown to be run-off ribosomal units. The incorporation of amino acids by a cell-free system is not affected by nalidixic acid. In nonproliferating cells the incorporation was also not prevented, unless the cells were previously incubated with the drug. These results are discussed in terms of the possible mechanism of action of nalidixic acid in T. pyriformis. PMID:807153

  20. Amino Acid and Protein Metabolism in Bermuda Grass During Water Stress 12

    PubMed Central

    Barnett, N. M.; Naylor, A. W.

    1966-01-01

    The ability of Arizona Common and Coastal Bermuda grass [Cynodon dactylon (L.) Pers.] to synthesize amino acids and proteins during water stress was investigated. Amino acids were continually synthesized during the water stress treatments, but protein synthesis was inhibited and protein levels decreased. Water stress induced a 10- to 100-fold accumulation of free proline in shoots and a 2- to 6-fold accumulation of free asparagine, both of which are characteristic responses of water-stressed plants. Valine levels increased, and glutamic acid and alanine levels decreased. 14C labeling experiments showed that free proline turns over more slowly than any other free amino acid during water stress. This proline is readily synthesized and accumulated from glutamic acid. It is suggested that during water stress free proline functions as a storage compound. No significant differences were found in the amino acid and protein metabolism of the 2 varieties of Bermuda grass. PMID:16656387

  1. Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast

    PubMed Central

    Misra, Ashish; Conway, Matthew F.; Johnnie, Joseph; Qureshi, Tabish M.; Lige, Bao; Derrick, Anne M.; Agbo, Eddy C.; Sriram, Ganesh

    2013-01-01

    Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA) in yeast. First, in silico extreme pathway (ExPa) analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP) as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing ExPas to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C) or the NADPH-malic enzyme ME2 (YKL029C) are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W) and an aspartate aminotransferase (YKL106W), and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple non-trivial metabolic engineering strategies for improving DHA yield in yeast. PMID:23898325

  2. Adenosine phosphonoacetic acid is slowly metabolized by NDP kinase.

    PubMed

    Chen, Y; Morera, S; Pasti, C; Angusti, A; Solaroli, N; Véron, M; Janin, J; Manfredini, S; Deville-Bonne, D

    2005-11-01

    NDP kinase catalyzes the last step in the phosphorylation of nucleotides. It is also involved in the activation by cellular kinases of nucleoside analogs used in antiviral therapies. Adenosine phosphonoacetic acid, a close analog of ADP already proposed as an inhibitor of ribonucleotide reductase, was found to be a poor substrate for human NDP kinase, as well as a weak inhibitor with an equilibrium dissociation constant of 0.6 mM to be compared to 0.025 mM for ADP. The X-ray structure of a complex of adenosine phosphonoacetic acid and the NDP kinase from Dictyostelium was determined to 2.0 A resolution showing that the analog adopts a binding mode similar to ADP, but that no magnesium ion is present at the active site. As ACP may also interfere with other cellular kinases, its potential as a drug targeting NDP kinase or ribonucleotide reductase is likely to be limited due to strong side effects. The design of new molecules with a narrower specificity and a stronger affinity will benefit from the detailed knowledge of the complex ACP-NDP kinase.

  3. Good and bad consequences of altered fatty acid metabolism in heart failure: evidence from mouse models.

    PubMed

    Abdurrachim, Desiree; Luiken, Joost J F P; Nicolay, Klaas; Glatz, Jan F C; Prompers, Jeanine J; Nabben, Miranda

    2015-05-01

    The shift in substrate preference away from fatty acid oxidation (FAO) towards increased glucose utilization in heart failure has long been interpreted as an oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted approach to treat heart failure. However, recent data indicate that increased reliance on glucose might be detrimental rather than beneficial for the failing heart. This review discusses new insights into metabolic adaptations in heart failure. A particular focus lies on data obtained from mouse models with modulations of cardiac FA metabolism at different levels of the FA metabolic pathway and how these differently affect cardiac function. Based on studies in which these mouse models were exposed to ischaemic and non-ischaemic heart failure, we discuss whether and when modulations in FA metabolism are protective against heart failure.

  4. Fermentative production of branched chain amino acids: a focus on metabolic engineering.

    PubMed

    Park, Jin Hwan; Lee, Sang Yup

    2010-01-01

    The branched chain amino acids (BCAAs), L-valine, L-leucine, and L-isoleucine, have recently been attracting much attention as their potential to be applied in various fields, including animal feed additive, cosmetics, and pharmaceuticals, increased. Strategies for developing microbial strains efficiently producing BCAAs are now in transition toward systems metabolic engineering from random mutagenesis. The metabolism and regulatory circuits of BCAA biosynthesis need to be thoroughly understood for designing system-wide metabolic engineering strategies. Here we review the current knowledge on BCAAs including their biosynthetic pathways, regulations, and export and transport systems. Recent advances in the development of BCAA production strains are also reviewed with a particular focus on L-valine production strain. At the end, the general strategies for developing BCAA overproducers by systems metabolic engineering are suggested.

  5. Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology.

    PubMed

    Pedersen, Martin B; Gaudu, Philippe; Lechardeur, Delphine; Petit, Marie-Agnès; Gruss, Alexandra

    2012-01-01

    The lactic acid bacteria (LAB) are essential for food fermentations and their impact on gut physiology and health is under active exploration. In addition to their well-studied fermentation metabolism, many species belonging to this heterogeneous group are genetically equipped for respiration metabolism. In LAB, respiration is activated by exogenous heme, and for some species, heme and menaquinone. Respiration metabolism increases growth yield and improves fitness. In this review, we aim to present the basics of respiration metabolism in LAB, its genetic requirements, and the dramatic physiological changes it engenders. We address the question of how LAB acquired the genetic equipment for respiration. We present at length how respiration can be used advantageously in an industrial setting, both in the context of food-related technologies and in novel potential applications.

  6. Medium-chain fatty acids: functional lipids for the prevention and treatment of the metabolic syndrome.

    PubMed

    Nagao, Koji; Yanagita, Teruyoshi

    2010-03-01

    Metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose, that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of medium-chain fatty acids (MCFAs) and medium-chain triglycerides (MCTs) in the development of metabolic syndrome. Experimental studies demonstrate that dietary MCFAs/MCTs suppress fat deposition through enhanced thermogenesis and fat oxidation in animal and human subjects. Additionally, several reports suggest that MCFAs/MCTs offer the therapeutic advantage of preserving insulin sensitivity in animal models and patients with type 2 diabetes.

  7. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    PubMed Central

    Meng, Shengxi; Cao, Jianmei; Feng, Qin; Peng, Jinghua; Hu, Yiyang

    2013-01-01

    Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism. PMID:24062792

  8. Effects of Light Quantity and Quality on the Decarboxylation of Malic Acid in Crassulacean Acid Metabolism Photosynthesis 1

    PubMed Central

    Barrow, Simon R.; Cockburn, William

    1982-01-01

    The rate of malic acid consumption in the Crassulacean acid metabolism (CAM) plant Kalanchoë daigremontiana Hamet et Perrier was found to be more rapid than the rate of photosynthetic oxygen evolution under all levels of irradiation by white light. This accounts for the accumulation of carbon dioxide in CAM tissues in the light. Action spectra of malate consumption and photosynthetic oxygen evolution in Kalanchoë were similar. Experiments using monochromatic photosynthetically active light in addition to a range of narrow waveband irradiations demonstrated that malic acid consumption in the experiments from which the action spectrum of acid consumption was constructed was not limited by the rate of photosynthesis. These data indicate that light involved in the promotion of malate consumption in CAM is absorbed by the same pigments that absorb the light which powers photosynthesis. PMID:16662250

  9. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut

    PubMed Central

    Ridlon, Jason M.; Kang, Dae-Joong; Hylemon, Phillip B.; Bajaj, Jasmohan S

    2015-01-01

    The understanding of the complex role of the bile acid-gut microbiome axis in health and disease processes is evolving rapidly. Our focus revolves around the interaction of the gut microbiota with liver diseases, especially cirrhosis. The bile acid pool size has recently been shown to be a function of microbial metabolism of bile acid and regulation of the microbiota by bile acids is important in the development and progression of several liver diseases. Humans produce a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of FXR in intestine and liver. Microbes use bile acids, and via FXR signaling this results in a smaller, unconjugated hydrophobic bile acid pool. This equilibrium is critical to maintain health. The challenge is to examine the manifold functions of gut bile acids as modulators of antibiotic, probiotic and disease progression in cirrhosis, metabolic syndrome and alcohol use. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. With advancing liver disease and cirrhosis, there is dysbiosis in the fecal, ileal and colonic mucosa, in addition to a decrease in bile acid concentration in the intestine due to the liver problems. This results in a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of deoxycholic acid (DCA). Alcohol intake speeds up these processes in the subjects with and without cirrhosis without significant FXR feedback. Taken together, these pathways can impact intestinal and systemic inflammation while worsening dysbiosis. The interaction between bile acids, alcohol, cirrhosis and dysbiosis is an important relationship that influences intestinal and systemic inflammation, which in turn determines progression of the overall disease process. These interactions and the impact of commonly used therapies for liver disease can provide insight into the pathogenesis

  10. Altered Retinoic Acid Metabolism in Diabetic Mouse Kidney Identified by 18O Isotopic Labeling and 2D Mass Spectrometry

    PubMed Central

    Starkey, Jonathan M.; Zhao, Yingxin; Sadygov, Rovshan G.; Haidacher, Sigmund J.; LeJeune, Wanda S.; Dey, Nilay; Luxon, Bruce A.; Kane, Maureen A.; Napoli, Joseph L.; Denner, Larry; Tilton, Ronald G.

    2010-01-01

    Background Numerous metabolic pathways have been implicated in diabetes-induced renal injury, yet few studies have utilized unbiased systems biology approaches for mapping the interconnectivity of diabetes-dysregulated proteins that are involved. We utilized a global, quantitative, differential proteomic approach to identify a novel retinoic acid hub in renal cortical protein networks dysregulated by type 2 diabetes. Methodology/Principal Findings Total proteins were extracted from renal cortex of control and db/db mice at 20 weeks of age (after 12 weeks of hyperglycemia in the diabetic mice). Following trypsinization, 18O- and 16O-labeled control and diabetic peptides, respectively, were pooled and separated by two dimensional liquid chromatography (strong cation exchange creating 60 fractions further separated by nano-HPLC), followed by peptide identification and quantification using mass spectrometry. Proteomic analysis identified 53 proteins with fold change ≥1.5 and p≤0.05 after Benjamini-Hochberg adjustment (out of 1,806 proteins identified), including alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (RALDH1/ALDH1A1). Ingenuity Pathway Analysis identified altered retinoic acid as a key signaling hub that was altered in the diabetic renal cortical proteome. Western blotting and real-time PCR confirmed diabetes-induced upregulation of RALDH1, which was localized by immunofluorescence predominantly to the proximal tubule in the diabetic renal cortex, while PCR confirmed the downregulation of ADH identified with mass spectrometry. Despite increased renal cortical tissue levels of retinol and RALDH1 in db/db versus control mice, all-trans-retinoic acid was significantly decreased in association with a significant decrease in PPARβ/δ mRNA. Conclusions/Significance Our results indicate that retinoic acid metabolism is significantly dysregulated in diabetic kidneys, and suggest that a shift in all-trans-retinoic acid metabolism is a novel feature in

  11. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control

    PubMed Central

    Xu, Peng; Li, Lingyun; Zhang, Fuming; Stephanopoulos, Gregory; Koffas, Mattheos

    2014-01-01

    Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA–derived compounds. PMID:25049420

  12. Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example.

    PubMed

    Badr, Haitham A; AlSadek, Dina M M; El-Houseini, Motawa E; Saeui, Christopher T; Mathew, Mohit P; Yarema, Kevin J; Ahmed, Hafiz

    2017-02-01

    Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an "Achilles' heel" that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural monosaccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer "sialome" they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.

  13. The metabolism of phenolic acids in the rat

    PubMed Central

    Ranganathan, S.; Ramasarma, T.

    1974-01-01

    Some of the enzyme systems in the formation of p-hydroxybenzoate from tyrosine have been studied in the rat liver in vitro. The conversion of p-hydroxycinnamate into p-hydroxybenzoate, which was found in rat liver mitochondria showed a number of differences when compared with the β-oxidation of fatty acids. Studies with p-hydroxy[U-14C]cinnamate indicated that 14CO2 was released during the formation of p-hydroxybenzoate. The formation of p-hydroxycinnamate from tyrosine of p-hydroxyphenyl-lactate could not be demonstrated in vitro. The interconversion of p-hydroxycinnamate and p-hydroxyphenylpropionate was demonstrated in rat liver mitochondria. PMID:4447627

  14. Monochloramine potently inhibits arachidonic acid metabolism in rat platelets.

    PubMed

    Fujimoto, Yohko; Ikeda, Mai; Sakuma, Satoru

    2006-05-26

    In the present study, the effects of hypochlorous acid (HOCl), monochloramine (NH(2)Cl), glutamine-chloramine (Glu-Cl) and taurine-chloramine (Tau-Cl) on the formation of 12-lipoxygenase (LOX) metabolite, 12-HETE, and cyclooxygenase (COX) metabolites, TXB(2), and 12-HHT, from exogenous arachidonic acid (AA) in rat platelets were examined. Rat platelets (4x10(8)/ml) were preincubated with drugs for 5min at 37 degrees C prior to the incubation with AA (40microM) for 2min at 37 degrees C. HOCl (50-250microM) showed an inhibition on the formation of LOX metabolite (12-HETE, 5-67% inhibition) and COX metabolites (TXB(2), 33-73% inhibition; 12-HHT, 27-74% inhibition). Although Tau-Cl and Glu-Cl up to 100microM were without effect on the formation of 12-HETE, TXB(2) and 12-HTT, NH(2)Cl showed a strong inhibition on the formation of all three metabolites (10-100microM NH(2)Cl, 12-HETE, 21-92% inhibition; TXB(2), 58-94% inhibition; 12-HHT, 36-92% inhibition). Methionine reversed a reduction of formation of LOX and COX metabolites induced by NH(2)Cl, and taurine restoring that induced by both NH(2)Cl and HOCl. These results suggest that NH(2)Cl is a more potent inhibitor of COX and LOX pathways in platelets than HOCl, and taurine and methionine can be modulators of NH(2)Cl-induced alterations in the COX and LOX pathways in vivo.

  15. Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain.

    PubMed

    Arias, B; Arufe, M; Alfonso, M; Duran, R

    1995-04-01

    Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

  16. KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism.

    PubMed

    Zhao, Erhu; Ding, Jane; Xia, Yingfeng; Liu, Mengling; Ye, Bingwei; Choi, Jeong-Hyeon; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Zha, Yunhong; Yang, Liqun; Cui, Hongjuan; Ding, Han-Fei

    2016-01-26

    The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9) trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation.

  17. HPLC analysis of in vivo intestinal absorption and oxidative metabolism of salicylic acid in the rat.

    PubMed

    Kuzma, Mónika; Nyúl, Eszter; Mayer, Mátyás; Fischer, Emil; Perjési, Pál

    2016-12-01

    In vivo absorption and oxidative metabolism of salicylic acid in rat small intestine was studied by luminal perfusion experiment. Perfusion through the lumen of proximal jejunum with isotonic medium containing 250 μm sodium salicylate was carried out. Absorption of salicylate was measured by a validated HPLC-DAD method which was evaluated for a number of validation characteristics (specificity, repeatability and intermediate precision, limit of detection, limit of quantification, linearity and accuracy). The method was linear over the concentration range 0.5-50 μg/mL. After liquid-liquid extraction of the perfusion samples oxidative biotransformation of salicylate was also investigated by HPLC-MS. The method was linear over the concentration range 0.25-5.0 μg/mL. Two hydroxylated metabolites of salicylic acid (2,5-dihydroxybenzoic acid and 2,3-dihydroxybenzoic acid) were detected and identified. The mean recovery of extraction was 72.4% for 2,3-DHB, 72.5% for 2,5-DHB and 50.1% for salicylic acid, respectively. The methods were successfully applied to investigate jejunal absorption and oxidative metabolism of sodium salicylate in experimental animals. The methods provide analytical background for further metabolic studies of salycilates under modified physiological conditions.

  18. KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism

    PubMed Central

    Xia, Yingfeng; Liu, Mengling; Ye, Bingwei; Choi, Jeong-Hyeon; Yan, Chunhong; Dong, Zheng; Huang, Shuang; Zha, Yunhong; Yang, Liqun; Cui, Hongjuan; Ding, Han-Fei

    2015-01-01

    SUMMARY The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in intracellular amino acid levels. Examination of the serine-glycine synthesis pathway reveals that KDM4C epigenetically activates the pathway genes under steady-state and serine deprivation conditions by removing the repressive histone modification H3 lysine 9 (H3K9) trimethylation. This action of KDM4C requires ATF4, a transcriptional master regulator of amino acid metabolism and stress responses. KDM4C activates ATF4 transcription and interacts with ATF4 to target serine pathway genes for transcriptional activation. We further present evidence for KDM4C in transcriptional coordination of amino acid metabolism and cell proliferation. These findings suggest a molecular mechanism linking KDM4C-mediated H3K9 demethylation and ATF4-mediated transactivation in reprogramming amino acid metabolism for cancer cell proliferation. PMID:26774480

  19. Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway.

    PubMed

    Sun, Runbin; Yang, Na; Kong, Bo; Cao, Bei; Feng, Dong; Yu, Xiaoyi; Ge, Chun; Huang, Jingqiu; Shen, Jianliang; Wang, Pei; Feng, Siqi; Fei, Fei; Guo, Jiahua; He, Jun; Aa, Nan; Chen, Qiang; Pan, Yang; Schumacher, Justin D; Yang, Chung S; Guo, Grace L; Aa, Jiye; Wang, Guangji

    2017-02-01

    Previous studies suggest that the lipid-lowering effect of berberine (BBR) involves actions on the low-density lipoprotein receptor and the AMP-activated protein kinase signaling pathways. However, the implication of these mechanisms is unclear because of the low bioavailability of BBR. Because the main action site of BBR is the gut and intestinal farnesoid X receptor (FXR) plays a pivotal role in the regulation of lipid metabolism, we hypothesized that the effects of BBR on intestinal FXR signaling pathway might account for its pharmacological effectiveness. Using wild type (WT) and intestine-specific FXR knockout (FXR(int-/-)) mice, we found that BBR prevented the development of high-fat-diet-induced obesity and ameliorated triglyceride accumulation in livers of WT, but not FXR(int-/-) mice. BBR increased conjugated bile acids in serum and their excretion in feces. Furthermore, BBR inhibited bile salt hydrolase (BSH) activity in gut microbiota, and significantly increased the levels of tauro-conjugated bile acids, especially tauro-cholic acid(TCA), in the intestine. Both BBR and TCA treatment activated the intestinal FXR pathway and reduced the expression of fatty-acid translocase Cd36 in the liver. These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway. In summary, we provide the first evidence to suggest a new mechanism of BBR action in the intestine that involves, sequentially, inhibiting BSH, elevating TCA, and activating FXR, which lead to the suppression of hepatic expression of Cd36 that results in reduced uptake of long-chain fatty acids in the liver.

  20. Activation of phosphatidic acid metabolism of human erythrocyte membranes by perfringolysin O

    SciTech Connect

    Saito, M.; Ando, S.; Mitsui, K.; Homma, Y.; Takenawa, T.

    1986-05-29

    The effect of perfringolysin O on the lipid metabolism of human erythrocyte membranes was investigated. Erythrocytes were prelabeled with (/sup 3/H)arachidonic acid and (/sup 32/P)inorganic phosphate. In the presence of calcium ion (5.5 mM), the effect of perfringolysin O on lipid metabolism was very similar to that of an calcium-ionophore A23187. In the absence of calcium ion, the accumulation of phosphatidic acid and its following decreasing trend were observed during the reaction with the toxin. Such changes were not caused by filipin. These results suggest that perfringolysin O causes the activation of a diglyceride-phosphatidic acid cycle, which might be involved in the calcium transport.

  1. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson ... Physiology . 14th ed. Hoboken, NJ: John Wiley & Sons; 2014:chap ...

  2. Metabolism

    MedlinePlus

    ... El metabolismo Metabolism Basics Our bodies get the energy they need from food through metabolism, the chemical ... that convert the fuel from food into the energy needed to do everything from moving to thinking ...

  3. Phytic acid and raffinose series oligosaccharides metabolism in developing chickpea seeds.

    PubMed

    Zhawar, Vikramjit Kaur; Kaur, Narinder; Gupta, Anil Kumar

    2011-10-01

    Phytic acid and raffinose series oligosaccharides (RFOs) have anti-nutritional properties where phytic acid chelates minerals and reduces their bioavailability to humans and other animals, and RFOs cause flatulence. Both phytic acid and RFOs cannot be digested by monogastric animals and are released as pollutant-wastes. Efforts are being made to reduce the contents of these factors without affecting the viability of seeds. This will require a thorough understanding of their metabolism in different crops. Biosynthetic pathways of both metabolites though are interlinked but not well described. This study was made on metabolism of these two contents in developing chickpea (Cicer arietinum L cv GL 769) seeds. In this study, deposition of RFOs was found to occur before deposition of phytic acid. A decline in inorganic phosphorus and increase in phospholipid phosphorus and phytic acid was observed in seeds during development. Acid phosphatase was the major phosphatase in seed as well as podwall and its activity was highest at early stage of development, thereafter it decreased. Partitioning of (14) C label from (14) C-glucose and (14) C-sucrose into RFOs and phytic acid was studied in seeds in presence of inositol, galactose and iositol and galactose, which favored the view that galactinol synthase is not the key enzyme in RFOs synthesis.

  4. Lysophosphatidic acid metabolism and elimination in cardiovascular disease

    NASA Astrophysics Data System (ADS)

    Salous, Abdelghaffar Kamal

    The bioactive lipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are present in human and mouse plasma at a concentration of ~0.1-1 microM and regulate physiological and pathophysiological processes in the cardiovascular system including atherothrombosis, intimal hyperplasia, and immune function, edema formation, and permeability. PPAP2B, the gene encoding LPP3, a broad activity integral membrane enzyme that terminates LPA actions in the vasculature, has a single nucleotide polymorphism that been recently associated with coronary artery disease risk. The synthesis and signaling of LPA and S1P in the cardiovascular system have been extensively studied but the mechanisms responsible for their elimination are less well understood. The broad goal of this research was to examine the role of LPP3 in the termination of LPA signaling in models of cardiovascular disease involving vascular wall cells, investigate the role of LPP3 in the elimination of plasma LPA, and further characterize the elimination of plasma LPA. The central hypothesis is that LPP3 plays an important role in attenuating the pathological responses to LPA signaling and that it mediates the elimination of exogenously applied bioactive lipids from the plasma. These hypotheses were tested using molecular biological approaches, in vitro studies, synthetic lysophospholipid mimetics, modified surgical procedures, and mass spectrometry assays. My results indicated that LPP3 played a critical role in attenuating LPA signaling mediating the pathological processes of intimal hyperplasia and vascular leak in mouse models of disease. Additionally, enzymatic inactivation of lysophospholipids by LPP and PLA enzymes in the plasma was not a primary mechanism for the rapid elimination of plasma LPA and S1P. Instead, evidence strongly suggested a transcellular uptake mechanism by hepatic non-parenchymal cells as the predominant mechanism for elimination of these molecules. These results support a model in

  5. Impacts of acute imipramine treatment on plasma and brain amino acid metabolism in mice given graded levels of dietary chicken protein.

    PubMed

    Nagasawa, Mao; Murakami, Tatsuro; Tomonaga, Shozo; Sato, Mikako; Takahata, Yoshihisa; Morimatsu, Fumiki; Furuse, Mitsuhiro

    2012-12-01

    Several studies have shown a relationship between depression and animal protein intake. To evaluate whether the difference of dietary chicken protein levels induces an antidepressant-like effect and potentiates acute antidepressant effects, three levels of dietary chicken protein were used as the representative animal protein with imipramine used as the antidepressant. In addition, the effects of dietary chicken protein on brain metabolism were evaluated. Open field test (OFT) and forced swimming test (FST) were conducted on the 27th and 28th days, respectively. OFT and FST were not influenced by both imipramine and dietary protein levels. However, characteristic effects of imipramine treatment on brain monoamine metabolism were observed in the cerebral cortex and hypothalamus. In addition, dietary protein significantly increased taurine and L-ornithine levels even though these amino acids were not contained in the diets. In conclusion, the metabolism of several amino acids in the plasma and brain were altered by dietary chicken protein.

  6. Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

    PubMed Central

    Dawson, Deborah V.; Blanchette, Derek R.; Drake, David R.; Wertz, Philip W.; Brogden, Kim A.

    2015-01-01

    ABSTRACT Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C16:1Δ6) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls. In this study, we further examined whole-cell protein differences between sapienic acid-treated bacteria and untreated controls, and we utilized open-source functional association and annotation programs to explore potential mechanisms for the antimicrobial activity of sapienic acid. Our analyses indicated that sapienic acid treatment induces a unique stress response in P. gingivalis resulting in differential expression of proteins involved in a variety of metabolic pathways. This network of differentially regulated proteins was enriched in protein-protein interactions (P = 2.98 × 10−8), including six KEGG pathways (P value ranges, 2.30 × 10−5 to 0.05) and four Gene Ontology (GO) molecular functions (P value ranges, 0.02 to 0.04), with multiple suggestive enriched relationships in KEGG pathways and GO molecular functions. Upregulated metabolic pathways suggest increases in energy production, lipid metabolism, iron acquisition and processing, and respiration. Combined with a suggested preferential metabolism of serine, which is necessary for fatty acid biosynthesis, these data support our previous findings that the site of sapienic acid antimicrobial activity is likely at the bacterial membrane. IMPORTANCE P. gingivalis is an important opportunistic pathogen implicated in periodontitis. Affecting nearly 50% of the population, periodontitis is treatable, but the resulting damage is irreversible and eventually progresses to tooth loss. There is a great need for natural products that can be used to treat and/or prevent the overgrowth of

  7. Metabolic regulation of the plant hormone indole-3-acetic acid

    SciTech Connect

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  8. Sulfur amino acid metabolism in Zucker diabetic fatty rats.

    PubMed

    Kwak, Hui Chan; Kim, Young-Mi; Oh, Soo Jin; Kim, Sang Kyum

    2015-08-01

    The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels.

  9. Chronic imipramine treatment differentially alters the brain and plasma amino acid metabolism in Wistar and Wistar Kyoto rats.

    PubMed

    Nagasawa, Mao; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

    2015-09-05

    In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.

  10. Vegetable oil blends with α-linolenic acid rich Garden cress oil modulate lipid metabolism in experimental rats.

    PubMed

    Umesha, S S; Naidu, K Akhilender

    2012-12-15

    Vegetable oil blends with modified fatty acid profile are being developed to improve n-6/n-3 polyunsaturated fatty acid (PUFAs) ratio in edible oils. The objective of this study is to develop vegetable oil blends with α-linolenic acid (ALA) rich Garden cress oil (GCO) and assess their modulatory effect on lipid metabolism. Sunflower oil (SFO), Rice bran oil (RBO), Sesame oil (SESO) were blended with GCO at different ratios to obtain n-6/n-3 PUFA ratio of 2.3-2.6. Native and GCO blended oils were fed to Wistar rats at 10% level in the diet for 60 days. Serum and liver lipids showed significant decrease in Total cholesterol (TC), Triglyceride (TG), LDL-C levels in GCO and GCO blended oil fed rats compared to native oil fed rats. ALA, EPA, DHA contents were significantly increased while linoleic acid (LA), arachidonic acid (AA) levels decreased in different tissues of GCO and GCO blended oils fed rats. In conclusion, blending of vegetable oils with GCO increases ALA, decreases n-6 to n-3 PUFA ratio and beneficially modulates lipid profile.

  11. Wine lees modulate lipid metabolism and induce fatty acid remodelling in zebrafish.

    PubMed

    Caro, M; Sansone, A; Amezaga, J; Navarro, V; Ferreri, C; Tueros, I

    2017-03-21

    This study investigates the ability of a polyphenolic extract obtained from a wine lees by-product to modulate zebrafish lipid metabolism. Lees from a Spanish winery were collected and the polyphenolic extract was chemically characterised in terms of antioxidant capacity, total phenolic content and the individual main phenolic compounds. The effects of the extract on lipid metabolism were evaluated using a zebrafish animal model. Lees are rich in polyphenols (42.33 mg gallic acid equivalent per g dry matter) with high antioxidant capacity (56.04 mg Trolox equivalent per g dry matter), rutin and quercetin being their main identified polyphenols. The biological effects of lees extract included (i) a reduction in zebrafish embryos' fat reserve (40%), (ii) changes in the expression of lipid metabolism key genes, (iii) remodelling of the fatty acid content in phospholipid and triglyceride fractions of zebrafish embryos and (iv) reduction in the trans fatty acid content. On the whole, wine lees polyphenolic extract was effective at modulating zebrafish lipid metabolism evidencing remodelling effects and antioxidant properties that can be further developed for food innovation.

  12. Effect of dietary fatty acids on metabolic rate and nonshivering thermogenesis in golden hamsters.

    PubMed

    Jefimow, Małgorzata; Wojciechowski, Michał S

    2014-02-01

    Hibernating rodents prior to winter tend to select food rich in polyunsaturated fatty acids (PUFA). Several studies found that such diet may positively affect their winter energy budget by enhancing torpor episodes. However, the effect of composition of dietary fatty acids (FA) on metabolism of normothermic heterotherms is poorly understood. Thus we tested whether diets different in FA composition affect metabolic rate (MR) and the capacity for nonshivering thermogenesis (NST) in normothermic golden hamsters (Mesocricetus auratus). Animals were housed in outdoor enclosures from May 2010 to April 2011 and fed a diet enriched with PUFA (i.e., standard food supplemented weekly with sunflower and flax seeds) or with saturated and monounsaturated fatty acids (SFA/MUFA, standard food supplemented with mealworms). Since diet rich in PUFA results in lower MR in hibernating animals, we predicted that PUFA-rich diet would have similar effect on MR of normothermic hamsters, that is, normothermic hamsters on the PUFA diet would have lower metabolic rate in cold and higher NST capacity than hamsters supplemented with SFA/MUFA. Indeed, in winter resting metabolic rate (RMR) below the lower critical temperature was higher and NST capacity was lower in SFA/MUFA-supplemented animals than in PUFA-supplemented ones. These results suggest that the increased capacity for NST in PUFA-supplemented hamsters enables them lower RMR below the lower critical temperature of the thermoneural zone.

  13. Metabolic diversity in biohydrogenation of polyunsaturated fatty acids by lactic acid bacteria involving conjugated fatty acid production.

    PubMed

    Kishino, Shigenobu; Ogawa, Jun; Yokozeki, Kenzo; Shimizu, Sakayu

    2009-08-01

    Lactobacillus plantarum AKU 1009a effectively transforms linoleic acid to conjugated linoleic acids of cis-9,trans-11-octadecadienoic acid (18:2) and trans-9,trans-11-18:2. The transformation of various polyunsaturated fatty acids by washed cells of L. plantarum AKU 1009a was investigated. Besides linoleic acid, alpha-linolenic acid [cis-9,cis-12,cis-15-octadecatrienoic acid (18:3)], gamma-linolenic acid (cis-6,cis-9,cis-12-18:3), columbinic acid (trans-5,cis-9,cis-12-18:3), and stearidonic acid [cis-6,cis-9,cis-12,cis-15-octadecatetraenoic acid (18:4)] were found to be transformed. The fatty acids transformed by the strain had the common structure of a C18 fatty acid with the cis-9,cis-12 diene system. Three major fatty acids were produced from alpha-linolenic acid, which were identified as cis-9,trans-11,cis-15-18:3, trans-9,trans-11,cis-15-18:3, and trans-10,cis-15-18:2. Four major fatty acids were produced from gamma-linolenic acid, which were identified as cis-6,cis-9,trans-11-18:3, cis-6,trans-9,trans-11-18:3, cis-6,trans-10-18:2, and trans-10-octadecenoic acid. The strain transformed the cis-9,cis-12 diene system of C18 fatty acids into conjugated diene systems of cis-9,trans-11 and trans-9,trans-11. These conjugated dienes were further saturated into the trans-10 monoene system by the strain. The results provide valuable information for understanding the pathway of biohydrogenation by anaerobic bacteria and for establishing microbial processes for the practical production of conjugated fatty acids, especially those produced from alpha-linolenic acid and gamma-linolenic acid.

  14. Metabolism of oleic acid in differentiating BFC-1 preadipose cells.

    PubMed

    Abumrad, N A; Forest, C; Regen, D M; Barnella, U S; Melki, S A

    1991-07-01

    Incorporation of [3H]oleate and [14C]glucose into cellular lipids was studied in the preadipose cell line BFC-1 to determine flux changes that accompany the adipose conversion process. Dilution of oleate by intracellular fatty acids (FA) was estimated from the 3H/14C incorporation ratios and from relating steady-state radioactivity in diglycerides to their measured cellular levels. The data indicated that exogenous FA mixed with less than 1% of endogenous FA on its pathway to esterification. Conversion of preadipocytes to adipocytes increased uptake of FA and glucose by approximately 3-fold and synthesis of diglycerides and triglycerides by 5- and 16-fold, respectively, with little if any increase of phospholipid synthesis. A 50% drop in 3H/14C incorporation ratio indicated a doubling of the rate at which endogenous FA mixed with the exogenous FA that had entered the cell. Adipocytes compared with preadipocytes exhibited a 50% greater cell diameter and a doubling of intracellular water volume and of protein and phospholipid levels, reflecting cellular enlargement consequent to the arrest of cell division that precedes adipose conversion. Diglyceride levels were also increased in adipocytes, however, since their turnover was fast, as indicated by rapid equilibration of diglyceride labeling; the increase reflected changes in their relative rates of synthesis and disposal. Diglyceride levels related to cell phospholipid, and other indexes of cell size remained constant. This indicated that the supply of diglycerides was tightly coupled to the synthesis of triglycerides and phospholipids, which suggested feedback regulation of diglyceride formation. The studies provide a methodological approach to measurement and interpretation of rates of lipid deposition in cultured cells.

  15. Serum Phospholipid Docosahexaenoic Acid Is Inversely Associated with Arterial Stiffness in Metabolically Healthy Men

    PubMed Central

    Lee, Mi-Hyang; Kwon, Nayeon; Yoon, So Ra

    2016-01-01

    We hypothesized that lower proportion of serum phospholipid docosahexaenoic acid (DHA) is inversely associated with increased cardiovascular risk and vascular function in metabolically healthy men. To elucidate it, we first compared serum phospholipid free fatty acid (FA) compositions and cardiovascular risk parameters between healthy men (n = 499) and male patients with coronary artery disease (CAD, n = 111) (30-69 years) without metabolic syndrome, and then further-analyzed the association of serum phospholipid DHA composition with arterial stiffness expressed by brachial-ankle pulse wave velocity (ba-PWV) in metabolically healthy men. Basic parameters, lipid profiles, fasting glycemic status, adiponectin, high sensitivity C-reactive protein (hs-CRP) and LDL particle size, and serum phospholipid FA compositions were significantly different between the two subject groups. Serum phospholipid DHA was highly correlated with most of long-chain FAs. Metabolically healthy men were subdivided into tertile groups according to serum phospholipid DHA proportion: lower (< 2.061%), middle (2.061%-3.235%) and higher (> 3.235%). Fasting glucose, insulin resistance, hs-CRP and ba-PWVs were significantly higher and adiponectin and LDL particle size were significantly lower in the lower-DHA group than the higher-DHA group after adjusted for confounding factors. In metabolically healthy men, multiple stepwise regression analysis revealed that serum phospholipid DHA mainly contributed to arterial stiffness (β′-coefficients = -0.127, p = 0.006) together with age, systolic blood pressure, triglyceride (r = 0.548, p = 0.023). Lower proportion of serum phospholipid DHA was associated with increased cardiovascular risk and arterial stiffness in metabolically healthy men. It suggests that maintaining higher proportion of serum phospholipid DHA may be beneficial for reducing cardiovascular risk including arterial stiffness in metabolically healthy men. PMID:27482523

  16. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  17. The role of holotrichs in the metabolism of dietary linoleic acid in the rumen.

    PubMed

    Girard, V; Hawke, J C

    1978-01-27

    The uptake and metabolism of linoleic acid by rumen holotrichs (mainly Isotricha prostoma and I. intestinalis) has been examined in in vitro infusion experiments. Maximum absorption and metabolism of [1-14C]linoleate by 2 . 10(6) Isotricha suspended in 100 ml buffer was obtained using an infusion rate of 1.6 mg linoleate/h. After 90 min, 84% of the added substrate was recovered within the cells, mainly as free fatty acid or phospholipid. There was a rapid incorporation of radioactivity into phospholipid, mainly phosphatidylcholine, at the commencement of linoleate infusion but no further incorporation after about 40 min. The presence of bacteria during incubations, in approximately the same Isotricha/bacteria ratio as found in the rumen, reduced the uptake of linoleate and the accumulation of free fatty acid by holotrichs but the incorporation into phospholipid remained similar to that obtained in the absence of bacteria. Very little biohydrogenation of linoleic acid occurred in incubations with holotrichs alone. Bacterial suspensions converted linoleic acid to mainly trans monoene and a small amount of stearic acid, but in incubations containing both bacteria and holotrichs, both stearic acid and trans monoene were major products. Using the latter mixed culture, about 20% of the added [1-14C]linoleic acid was present in holotrich phospholipid of which 62% remained as octadecadienoic acid. The Isotricha population was 3 . 10(3)--2 . 10(4)/ml rumen fluid and it contributed about 23% of the linoleic acid in the rumen of a cow on a hay diet.

  18. [Nutrition, acid-base metabolism, cation-anion difference and total base balance in humans].

    PubMed

    Mioni, R; Sala, P; Mioni, G

    2008-01-01

    The relationship between dietary intake and acid-base metabolism has been investigated in the past by means of the inorganic cation-anion difference (C(+)(nm)-A(-)(nm)) method based on dietary ash-acidity titration after the oxidative combustion of food samples. Besides the inorganic components of TA (A(-)(nm)-C(+)(nm)), which are under renal control, there are also metabolizable components (A(-)(nm)-C(+)(nm)) of TA, which are under the control of the intermediate metabolism. The whole body base balance, NBb(W), is obtained only by the application of C(+)(nm)-A(-)(nm) to food, feces and urine, while the metabolizable component (A(-)(nm)-C(+)(nm)) is disregarded. A novel method has been subsequently suggested to calculate the net balance of fixed acid, made up by the difference between the input of net endogenous acid production: NEAP = SO(4)(2-)+A(-)(m)-(C(+)(nm)-A(-)(nm)), and the output of net acid excretion: NAE = TA + NH(4)(+) - HCO(3)(-). This approach has been criticized because 1) it includes metabolizable acids, whose production cannot be measured independently; 2) the specific control of metabolizable acid and base has been incorrectly attributed to the kidney; 3) the inclusion of A-m in the balance input generates an acid overload; 4) the object of measurement in making up a balance has to be the same, a condition not fulfilled as NEAP is different from NAE. Lastly, by rearranging the net balance of the acid equation, the balance of nonmetabolizable acid equation is obtained. Therefore, any discrepancy between these two equations is due to the inaccuracy in the urine measurement of metabolizable cations and/or anions.

  19. Metabolism of branched-chain keto acids in neonatal rat liver perfusions.

    PubMed

    Frost, S C; Wells, M A

    1983-10-15

    The ability of the neonatal rat to oxidize the branched-chain amino acids leucine and valine and their corresponding keto acids was evaluated. In vivo, about 20% of orally administered labeled amino or keto acids were oxidized in 6 h, after which time little further oxidation occurred. In perfused neonatal liver the amino acids were oxidized at only 5-10% the rate of the keto acids. The oxidation of the keto acids showed a saturable dependence on concentration. The decarboxylation of ketoisocaproate (KIC) had a maximal rate of 40.1 +/- 1.6 mumol/h/g liver with an apparent Km of 0.27 +/- 0.03 mM, and decarboxylation of ketoisovalerate (KIV) had a maximal rate of 37.9 +/- 1.9 mumol/h/g liver and an apparent Km of 0.28 +/- 0.04 mM. KIC was ketogenic, producing mainly acetoacetate at a maximal rate of 44.5 +/- 1.6 mumol/h/g liver with an apparent Km of 0.27 +/- 0.03 mM. On the other hand, KIV was not gluconeogenic, although the perfused neonatal liver was able to produce glucose from lactate. During liver perfusion, KIV did not produce measurable quantities of either propionic or beta-aminoisobutyric acids, which are possible end products of KIV metabolism. Decanoic acid inhibited the decarboxylation of both keto acids to the same extent with a maximal effect at 0.4 mM fatty acid. At saturating levels, KIC was less ketogenic than decanoate. Inhibition of endogenous fatty acid oxidation by 2-tetradecylglycidic acid had no effect on keto acid oxidation. These data suggest that branched-chain amino acids derived from milk proteins are probably not quantitatively significant sources of either ketone bodies or glucose in the neonatal rat.

  20. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders

    PubMed Central

    Burrage, Lindsay C.; Nagamani, Sandesh C.S.; Campeau, Philippe M.; Lee, Brendan H.

    2014-01-01

    Branched-chain amino acid (BCAA) metabolism plays a central role in the pathophysiology of both rare inborn errors of metabolism and the more common multifactorial diseases. Although deficiency of the branched-chain ketoacid dehydrogenase (BCKDC) and associated elevations in the BCAAs and their ketoacids have been recognized as the cause of maple syrup urine disease (MSUD) for decades, treatment options for this disorder have been limited to dietary interventions. In recent years, the discovery of improved leucine tolerance after liver transplantation has resulted in a new therapeutic strategy for this disorder. Likewise, targeting the regulation of the BCKDC activity may be an alternative potential treatment strategy for MSUD. The regulation of the BCKDC by the branched-chain ketoacid dehydrogenase kinase has also been implicated in a new inborn error of metabolism characterized by autism, intellectual disability and seizures. Finally, there is a growing body of literature implicating BCAA metabolism in more common disorders such as the metabolic syndrome, cancer and hepatic disease. This review surveys the knowledge acquired on the topic over the past 50 years and focuses on recent developments in the field of BCAA metabolism. PMID:24651065

  1. Valproic Acid as a Potentiator of Metabolic Syndrome In Institutionalized Residents on Concomitant Antipsychotics: Fat Chance, or Slim to None?

    PubMed Central

    Zuo, Silu; Fries, Brant E.; Szafara, Kristina; Regal, Randolph

    2015-01-01

    Background: Valproic acid (VPA) is one of the most commonly used antiepileptic medications worldwide; it is also a popular mood stabilizer for use in bipolar disorder and dementia. This study assessed whether VPA may potentiate metabolic side effects in patients with psychiatric disorders taking concomitant antipsychotics (APs). VPA alone has been associated with weight gain, dyslipidemia, hypertension, and diabetes. Patients with psychiatric disorders, especially those on second-generation (atypical) APs, appear to be at increased risk of these metabolic effects. A secondary purpose was to determine if a linear dose–response relationship exists between the VPA dose and adverse metabolic effects. Methods: This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m2); very high BMI (BMI greater than 40 kg/m2); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects. Results: Patients in the VPA plus APs group were 3.2 kg heavier than those in the APs group (P = 0.05) at baseline. Compared with the APs group, the VPA plus APs group had a higher prevalence of high and very high BMI, diabetes, hypertension, and the combination of any three factors of high BMI, hyperlipidemia/dyslipidemia, diabetes, and hypertension. However, these differences were not

  2. The Immunosuppressant Mycophenolic Acid Alters Nucleotide and Lipid Metabolism in an Intestinal Cell Model

    PubMed Central

    Heischmann, Svenja; Dzieciatkowska, Monika; Hansen, Kirk; Leibfritz, Dieter; Christians, Uwe

    2017-01-01

    The study objective was to elucidate the molecular mechanisms underlying the negative effects of mycophenolic acid (MPA) on human intestinal cells. Effects of MPA exposure and guanosine supplementation on nucleotide concentrations in LS180 cells were assessed using liquid chromatography-mass spectrometry. Proteomics analysis was carried out using stable isotope labeling by amino acids in cell culture combined with gel-based liquid chromatography-mass spectrometry and lipidome analysis using 1H nuclear magnetic resonance spectroscopy. Despite supplementation, depletion of guanosine nucleotides (p < 0.001 at 24 and 72 h; 5, 100, and 250 μM MPA) and upregulation of uridine and cytidine nucleotides (p < 0.001 at 24 h; 5 μM MPA) occurred after exposure to MPA. MPA significantly altered 35 proteins mainly related to nucleotide-dependent processes and lipid metabolism. Cross-reference with previous studies of MPA-associated protein changes widely corroborated these results, but showed differences that may be model- and/or method-dependent. MPA exposure increased intracellular concentrations of fatty acids, cholesterol, and phosphatidylcholine (p < 0.01 at 72 h; 100 μM MPA) which corresponded to the changes in lipid-metabolizing proteins. MPA affected intracellular nucleotide levels, nucleotide-dependent processes, expression of structural proteins, fatty acid and lipid metabolism in LS180 cells. These changes may compromise intestinal membrane integrity and contribute to gastrointestinal toxicity. PMID:28327659

  3. The heparan and heparin metabolism pathway is involved in regulation of fatty acid composition.

    PubMed

    Jiang, Zhihua; Michal, Jennifer J; Wu, Xiao-Lin; Pan, Zengxiang; MacNeil, Michael D

    2011-01-01

    Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1 (heparan sulfate 6-O-sulfotransferase 1), HS6ST3 (heparan sulfate 6-O-sulfotransferase 3), NDST3 (N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3), and SULT1A1 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1), were investigated for their associations with muscle lipid composition using cattle as a model organism. Nineteen single nucleotide polymorphisms (SNPs)/multiple nucleotide length polymorphisms (MNLPs) were identified in five of these six genes. Six of these mutations were then genotyped on 246 Wagyu x Limousin F(2) animals, which were measured for 5 carcass, 6 eating quality and 8 fatty acid composition traits. Association analysis revealed that DSEL, EXTL1 and HS6ST1 significantly affected two stearoyl-CoA desaturase activity indices, the amount of conjugated linoleic acid (CLA), and the relative amount of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in skeletal muscle (P<0.05). In particular, HS6ST1 joined our previously reported SCD1 and UQCRC1 genes to form a three gene network for one of the stearoyl-CoA desaturase activity indices. These results provide evidence that genes involved in heparan sulfate and heparin metabolism are also involved in regulation of lipid metabolism in bovine muscle. Whether the SNPs affected heparan sulfate proteoglycan structure is unknown and warrants further investigation.

  4. Emerging Perspectives on Essential Amino Acid Metabolism in Obesity and the Insulin-Resistant State12

    PubMed Central

    Adams, Sean H.

    2011-01-01

    Dysregulation of insulin action is most often considered in the context of impaired glucose homeostasis, with the defining feature of diabetes mellitus being elevated blood glucose concentration. Complications arising from the hyperglycemia accompanying frank diabetes are well known and epidemiological studies point to higher risk toward development of metabolic disease in persons with impaired glucose tolerance. Although the central role of proper blood sugar control in maintaining metabolic health is well established, recent developments have begun to shed light on associations between compromised insulin action [obesity, prediabetes, and type 2 diabetes mellitus (T2DM)] and altered intermediary metabolism of fats and amino acids. For amino acids, changes in blood concentrations of select essential amino acids and their derivatives, in particular BCAA, sulfur amino acids, tyrosine, and phenylalanine, are apparent with obesity and insulin resistance, often before the onset of clinically diagnosed T2DM. This review provides an overview of these changes and places recent observations from metabolomics research into the context of historical reports in the areas of biochemistry and nutritional biology. Based on this synthesis, a model is proposed that links the FFA-rich environment of obesity/insulin resistance and T2DM with diminution of BCAA catabolic enzyme activity, changes in methionine oxidation and cysteine/cystine generation, and tissue redox balance (NADH/NAD+). PMID:22332087

  5. Trehalose 6-phosphate coordinates organic and amino acid metabolism with carbon availability.

    PubMed

    Figueroa, Carlos M; Feil, Regina; Ishihara, Hirofumi; Watanabe, Mutsumi; Kölling, Katharina; Krause, Ursula; Höhne, Melanie; Encke, Beatrice; Plaxton, William C; Zeeman, Samuel C; Li, Zhi; Schulze, Waltraud X; Hoefgen, Rainer; Stitt, Mark; Lunn, John E

    2016-02-01

    Trehalose 6-phosphate (Tre6P) is an essential signal metabolite in plants, linking growth and development to carbon metabolism. The sucrose-Tre6P nexus model postulates that Tre6P acts as both a signal and negative feedback regulator of sucrose levels. To test this model, short-term metabolic responses to induced increases in Tre6P levels were investigated in Arabidopsis thaliana plants expressing the Escherichia coli Tre6P synthase gene (otsA) under the control of an ethanol-inducible promoter. Increased Tre6P levels led to a transient decrease in sucrose content, post-translational activation of nitrate reductase and phosphoenolpyruvate carboxylase, and increased levels of organic and amino acids. Radio-isotope ((14)CO2) and stable isotope ((13)CO2) labelling experiments showed no change in the rates of photoassimilate export in plants with elevated Tre6P, but increased labelling of organic acids. We conclude that high Tre6P levels decrease sucrose levels by stimulating nitrate assimilation and anaplerotic synthesis of organic acids, thereby diverting photoassimilates away from sucrose to generate carbon skeletons and fixed nitrogen for amino acid synthesis. These results are consistent with the sucrose-Tre6P nexus model, and implicate Tre6P in coordinating carbon and nitrogen metabolism in plants.

  6. Ca2+ channel blockade prevents lysergic acid diethylamide-induced changes in dopamine and serotonin metabolism.

    PubMed

    Antkiewicz-Michaluk, L; Románska, I; Vetulani, J

    1997-07-30

    To investigate the effect of a single and multiple administration of lysergic acid diethylamide (LSD) on cerebral metabolism of dopamine and serotonin, male Wistar rats were treated with low and high doses (0.1 and 2.0 mg/kg i.p.) of LSD and the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, serotonin and 5-hydroxyindoleacetic acid were assayed by HPLC in the nucleus accumbens, striatum and frontal cortex. Some rats received nifedipine, 5 mg/kg i.p., before each injection of LSD to assess the effect of a Ca2+ channel blockade. High-dose LSD treatment (8 x 2 mg/kg per day) caused a strong stimulation of dopamine metabolism in the nucleus accumbens and striatum, and serotonin metabolism in the nucleus accumbens: the changes were observed 24 (but not 1 h) after the last dose. The changes induced by the low-dose treatment (8 x 0.1 mg/kg per day) had a different pattern, suggesting the release of dopamine from vesicles to cytoplasm. Co-administration of nifedipine completely prevented the LSD-induced biochemical changes. The results suggest that Ca2+ channel blocking agents may prevent development of some behavioral consequences of chronically used LSD.

  7. Arterio-venous balance studies of skeletal muscle fatty acid metabolism: what can we believe?

    PubMed Central

    Guo, ZengKui

    2013-01-01

    The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infusion in healthy humans is somewhat unexpected (26). It appears that given the complex anatomy of human limbs, as to be discussed in this review, it is virtually impossible to determine whether any fatty acids being released into the venous circulation of an arm or leg derive from the lipolysis of intermuscular fat residing between muscle groups, intramuscular fat residing within muscle groups (between epimysium and perimysium, or bundles), or the intramyocellular triglyceride droplets (imcTG). In many cases, it may even be difficult to be confident that there is no contribution of FFA from subcutaneous adipose tissue. This question is fundamentally important as one attempts to interpret the results of skeletal muscle fatty acid metabolism studies using the A-V balance technique. In this Perspectives article, we examine the reported results of fatty acid kinetics obtained using the techniques to evaluate the degree of and how to minimize contamination when attempting to sample skeletal muscle-specific fatty acids. PMID:23941872

  8. The chromatin remodeler DDM1 promotes hybrid vigor by regulating salicylic acid metabolism.

    PubMed

    Zhang, Qingzhu; Li, Yanqiang; Xu, Tao; Srivastava, Ashish Kumar; Wang, Dong; Zeng, Liang; Yang, Lan; He, Li; Zhang, Heng; Zheng, Zhimin; Yang, Dong-Lei; Zhao, Cheng; Dong, Juan; Gong, Zhizhong; Liu, Renyi; Zhu, Jian-Kang

    2016-01-01

    In plants, hybrid vigor is influenced by genetic and epigenetic mechanisms; however, the molecular pathways are poorly understood. We investigated the potential contributions of epigenetic regulators to heterosis in Arabidposis and found that the chromatin remodeler DECREASED DNA METHYLATION 1 (DDM1) affects early seedling growth heterosis in Col/C24 hybrids. ddm1 mutants showed impaired heterosis and increased expression of non-additively expressed genes related to salicylic acid metabolism. Interestingly, our data suggest that salicylic acid is a hormetic regulator of seedling growth heterosis, and that hybrid vigor arises from crosses that produce optimal salicylic acid levels. Although DNA methylation failed to correlate with differential non-additively expressed gene expression, we uncovered DDM1 as an epigenetic link between salicylic acid metabolism and heterosis, and propose that the endogenous salicylic acid levels of parental plants can be used to predict the heterotic outcome. Salicylic acid protects plants from pathogens and abiotic stress. Thus, our findings suggest that stress-induced hormesis, which has been associated with increased longevity in other organisms, may underlie specific hybrid vigor traits.

  9. Metabolic engineering of microorganisms to produce omega-3 very long-chain polyunsaturated fatty acids.

    PubMed

    Gong, Yangmin; Wan, Xia; Jiang, Mulan; Hu, Chuanjiong; Hu, Hanhua; Huang, Fenghong

    2014-10-01

    Omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) have received growing attention due to their significant roles in human health. Currently the main source of these nutritionally and medically important fatty acids is marine fish, which has not met ever-increasing global demand. Microorganisms are an important alternative source also being explored. Although many microorganisms accumulate omega-3 LC-PUFAs naturally, metabolic engineering might still be necessary for significantly improving their yields. Here, we review recent research involving the engineering of microorganisms for production of omega-3 LC-PUFAs, including eicospentaenoic acid and docosohexaenoic acid. Both reconstitution of omega-3 LC-PUFA biosynthetic pathways and modification of existing pathways in microorganisms have demonstrated the potential to produce high levels of omega-3 LC-PUFAs. However, the yields of omega-3 LC-PUFAs in host systems have been substantially limited by potential metabolic bottlenecks, which might be caused partly by inefficient flux of fatty acid intermediates between the acyl-CoA and different lipid class pools. Although fatty acid flux in both native and heterologous microbial hosts might be controlled by several acyltransferases, evidence has suggested that genetic manipulation of one acyltransferase alone could significantly increase the accumulation of LC-PUFAs. The number of oleaginous microorganisms that can be genetically transformed is increasing, which will advance engineering efforts to maximize LC-PUFA yields in microbial strains.

  10. The chromatin remodeler DDM1 promotes hybrid vigor by regulating salicylic acid metabolism

    PubMed Central

    Zhang, Qingzhu; Li, Yanqiang; Xu, Tao; Srivastava, Ashish Kumar; Wang, Dong; Zeng, Liang; Yang, Lan; He, Li; Zhang, Heng; Zheng, Zhimin; Yang, Dong-Lei; Zhao, Cheng; Dong, Juan; Gong, Zhizhong; Liu, Renyi; Zhu, Jian-Kang

    2016-01-01

    In plants, hybrid vigor is influenced by genetic and epigenetic mechanisms; however, the molecular pathways are poorly understood. We investigated the potential contributions of epigenetic regulators to heterosis in Arabidposis and found that the chromatin remodeler DECREASED DNA METHYLATION 1 (DDM1) affects early seedling growth heterosis in Col/C24 hybrids. ddm1 mutants showed impaired heterosis and increased expression of non-additively expressed genes related to salicylic acid metabolism. Interestingly, our data suggest that salicylic acid is a hormetic regulator of seedling growth heterosis, and that hybrid vigor arises from crosses that produce optimal salicylic acid levels. Although DNA methylation failed to correlate with differential non-additively expressed gene expression, we uncovered DDM1 as an epigenetic link between salicylic acid metabolism and heterosis, and propose that the endogenous salicylic acid levels of parental plants can be used to predict the heterotic outcome. Salicylic acid protects plants from pathogens and abiotic stress. Thus, our findings suggest that stress-induced hormesis, which has been associated with increased longevity in other organisms, may underlie specific hybrid vigor traits. PMID:27551435

  11. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    SciTech Connect

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

    1986-03-05

    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  12. Technical note: stearidonic acid metabolism by mixed ruminal microorganisms in vitro.

    PubMed

    Maia, M R G; Correia, C A S; Alves, S P; Fonseca, A J M; Cabrita, A R J

    2012-03-01

    Dietary supplementation of stearidonic acid (SDA; 18:4n-3) has been considered a possible strategy to increase n-3 unsaturated fatty acid content in ruminant products; however, little is known about its metabolism in the rumen. In vitro batch incubations were carried out with bovine ruminal digesta to investigate the metabolism of SDA and its biohydrogenation products. Incubation mixtures (4.5 mL) that contained 0 (control), 0.25, 0.50, 0.75, 1.00, 1.25, or 1.50 mg of SDA supplemented to 33 mg (DM basis) of commercial total mixed ration based on corn silage, for dairy cows, were incubated for 72 h at 39°C. The content of most fatty acids in whole freeze-dried cultures was affected by SDA supplementation. Branched-chain fatty acids decreased linearly (P < 0.01), and odd-chain fatty acids decreased quadratically (P < 0.01), particularly from 1.00 mg of SDA and above, whereas most C18 fatty acids increased linearly or quadratically (P ≤ 0.04). Stearidonic acid concentrations at 72 h of incubation were very small (<0.6% of total fatty acids and ≤0.9% of added SDA) in all treatments. The apparent biohydrogenation of SDA was extensive, but it was not affected by SDA concentration (P > 0.05). Biohydrogenation followed a pattern similar to that of other C18 unsaturated fatty acids up to 1.00 mg of SDA. Stearic acid (18:0) and vaccenic acid (18:1 trans-11) were the major fatty acids formed, with the latter increasing 9-fold in the 1.00 mg of SDA treatment. At greater inclusion rates, 18:0 and 18:1 trans isomers decreased (P ≤ 0.03), accompanied by increases in unidentified 18:3 and 18:4 isomers (P = 0.02), suggesting that the biohydrogenation pathway was inhibited. The present results clearly indicate that SDA was metabolized extensively, with numerous 18:4 and 18:3 products formed en route to further conversion to 18:2, 18:1 isomers, and 18:0.

  13. Assessment of the Effects of Zoledronic Acid Therapy on Bone Metabolic Indicators in Hormone-Resistant Prostate Cancer Patients with Bone Metastatasis

    PubMed Central

    Demirtas, Abdullah; Sahin, Nurettin; Caniklioglu, Mehmet; Kula, Mustafa; Ekmekcioglu, Oguz; Tatlisen, Atila

    2011-01-01

    Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID:22084798

  14. Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells

    PubMed Central

    Angela, Mulki; Endo, Yusuke; Asou, Hikari K.; Yamamoto, Takeshi; Tumes, Damon J.; Tokuyama, Hirotake; Yokote, Koutaro; Nakayama, Toshinori

    2016-01-01

    To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. PPARγ directly binds and induces genes associated with fatty acid uptake in CD4+ T cells in both mice and humans. The PPARγ-dependent fatty acid uptake programme is critical for metabolic reprogramming. Thus, we provide important mechanistic insights into the metabolic reprogramming mechanisms that govern the expression of key enzymes, fatty acid metabolism and the acquisition of an activated phenotype during CD4+ T cell activation. PMID:27901044

  15. Transport and metabolic effects of alpha-aminoisobutyric acid in Saccharomyces cerevisiae.

    PubMed

    Kim, K W; Roon, R J

    1982-11-24

    alpha-Aminoisobutyric acid is actively transported into yeast cells by the general amino acid transport system. The system exhibits a Km for alpha-aminoisobutyric acid of 270 microM, a Vmax of 24 nmol/min per mg cells (dry weight), and a pH optimum of 4.1-4.3. alpha-Aminoisobutyric acid is also transported by a minor system(s) with a Vmax of 1.7 nmol/min per mg cells. Transport occurs against a concentration gradient with the concentration ratio reaching over 1000:1 (in/out). The alpha-aminoisobutyric acid is not significantly metabolized or incorporated into protein after an 18 h incubation. alpha-Aminoisobutyric acid inhibits cell growth when a poor nitrogen source such as proline is provided but not with good nitrogen sources such as NH+4. During nitrogen starvation alpha-aminoisobutyric acid strongly inhibits the synthesis of the nitrogen catabolite repression sensitive enzyme, asparaginase II. Studies with a mutant yeast strain (GDH-CR) suggest that alpha-aminoisobutyric acid inhibition of asparaginase II synthesis occurs because alpha-aminoisobutyric acid is an effective inhibitor of protein synthesis in nitrogen starved cells.

  16. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats.

    PubMed

    Khaire, Amrita; Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2015-08-01

    Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (p<0.01) but reduced docosahexaenoic acid (DHA) (p<0.05), liver mRNA levels of acetyl CoA carboxylase-1 (ACC-1) (p<0.05) and carnitine palmitoyltransferase-1 (CPT-1) (p<0.01) in the offspring. Omega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (p<0.01) and reduced liver mRNA levels of adiponectin, ACC-1, and CPT-1 (p<0.01 for all). Supplementation of both vitamin B12 and omega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.

  17. A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism.

    PubMed

    Cabruja, Matías; Mondino, Sonia; Tsai, Yi Ting; Lara, Julia; Gramajo, Hugo; Gago, Gabriela

    2017-02-01

    Unlike most bacteria, mycobacteria rely on the multi-domain enzyme eukaryote-like fatty acid synthase I (FAS I) to make fatty acids de novo. These metabolites are precursors of the biosynthesis of most of the lipids present both in the complex mycobacteria cell wall and in the storage lipids inside the cell. In order to study the role of the type I FAS system in Mycobacterium lipid metabolism in vivo, we constructed a conditional mutant in the fas-acpS operon of Mycobacterium smegmatis and analysed in detail the impact of reduced de novo fatty acid biosynthesis on the global architecture of the cell envelope. As expected, the mutant exhibited growth defect in the non-permissive condition that correlated well with the lower expression of fas-acpS and the concomitant reduction of FAS I, confirming that FAS I is essential for survival. The reduction observed in FAS I provoked an accumulation of its substrates, acetyl-CoA and malonyl-CoA, and a strong reduction of C12 to C18 acyl-CoAs, but not of long-chain acyl-CoAs (C19 to C24). The most intriguing result was the ability of the mutant to keep synthesizing mycolic acids when fatty acid biosynthesis was impaired. A detailed comparative lipidomic analysis showed that although reduced FAS I levels had a strong impact on fatty acid and phospholipid biosynthesis, mycolic acids were still being synthesized in the mutant, although with a different relative species distribution. However, when triacylglycerol degradation was inhibited, mycolic acid biosynthesis was significantly reduced, suggesting that storage lipids could be an intracellular reservoir of fatty acids for the biosynthesis of complex lipids in mycobacteria. Understanding the interaction between FAS I and the metabolic pathways that rely on FAS I products is a key step to better understand how lipid homeostasis is regulated in this microorganism and how this regulation could play a role during infection in pathogenic mycobacteria.

  18. [Metabolic engineering of wild acid-resistant yeast for L-lactic acid production].

    PubMed

    Zhang, Qin; Zhang, Liang; Ding, Zhongyang; Wang, Zhengxiang; Shi, Guiyang

    2011-07-01

    In order to obtain a yeast strain able to produce L-lactic acid under the condition of low pH and high lactate content, one wild acid-resistant yeast strain isolated from natural samples, was found to be able to grow well in YEPD medium (20 g/L glucose, 20 g/L tryptone, 10 g/L yeast extract, adjusted pH 2.5 with lactic acid) without consuming lactic acid. Based on further molecular biological tests, the strain was identified as Candida magnolia. Then, the gene ldhA, encoding a lactate dehydrogenase from Rhizopus oryzae, was cloned into a yeast shuttle vector containing G418 resistance gene. The resultant plasmid pYX212-kanMX-ldhA was introduced into C. magnolia by electroporation method. Subsequently, a recombinant L-lactic acid producing yeast C. magnolia-2 was obtained. The optimum pH of the recombinant yeast is 3.5 for lactic acid production. Moreover, the recombinant strain could grow well and produce lactic acid at pH 2.5. This recombinant yeast strain could be useful for producing L-lactic acid.

  19. Neutrophil chemotaxis and arachidonic acid metabolism are not linked: evidence from metal ion probe studies

    SciTech Connect

    Turner, S.R.; Turner, R.A.; Smith, D.M.; Johnson, J.A.

    1986-03-05

    Heavy metal ions can inhibit arachidonic acid (AA) metabolism protect against ionophore cytotoxicity (ibid) and inhibit neutrophil chemotaxis. In this study they used Au/sup 3 +/, Zn/sup 2 +/, Cr/sup 3 +/, Mn/sup 2 +/ and Cu/sup 2 +/ as probes of the interrelationships among AA metabolism, ionophore-mediated cytotoxicity, and chemotaxis. Phospholipid deacylation was measured in ionophore-treated cells prelabeled with /sup 3/H-AA. Eicosanoid release from ionophore-treated cells was monitored by radioimmunoassay. Cytoprotection was quantitated as ability to exclude trypan blue. Chemotaxis toward f-met-leu-phe was measured by leading front analysis. The results imply that metal ions attenuate ionophore cytotoxicity by blocking phospholipid deacylation and eicosanoid release. In contrast to previous reports, no correlation between AA metabolism and chemotaxis was demonstrated, suggesting that these 2 processes are not linked.

  20. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation.

    PubMed

    Kasubuchi, Mayu; Hasegawa, Sae; Hiramatsu, Takero; Ichimura, Atsuhiko; Kimura, Ikuo

    2015-04-14

    During feeding, the gut microbiota contributes to the host energy acquisition and metabolic regulation thereby influencing the development of metabolic disorders such as obesity and diabetes. Short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A) and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC). Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues. In this review, we summarize the roles of gut microbial SCFAs in the host energy regulation and present an overview of the current understanding of its physiological functions.

  1. Genetic Investigation of Tricarboxylic Acid Metabolism During the Plasmodium falciparum Lifecycle

    PubMed Central

    Ke, Hangjun; Lewis, Ian A.; Morrisey, Joanne M.; McLean, Kyle J.; Ganesan, Suresh M.; Painter, Heather J.; Mather, Michael W.; Jacobs-Lorena, Marcelo; Llinás, Manuel; Vaidya, Akhil B.

    2015-01-01

    SUMMARY New antimalarial drugs are urgently needed to control drug resistant forms of the malaria parasite, Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO) lines that delete six of the eight mitochondrial tricarboxylic acid (TCA) cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted lifecycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate dehydrogenase deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of 13C isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development. PMID:25843709

  2. Yeast genes involved in response to lactic acid and acetic acid: acidic conditions caused by the organic acids in Saccharomyces cerevisiae cultures induce expression of intracellular metal metabolism genes regulated by Aft1p.

    PubMed

    Kawahata, Miho; Masaki, Kazuo; Fujii, Tsutomu; Iefuji, Haruyuki

    2006-09-01

    Using two types of genome-wide analysis to investigate yeast genes involved in response to lactic acid and acetic acid, we found that the acidic condition affects metal metabolism. The first type is an expression analysis using DNA microarrays to investigate 'acid shock response' as the first step to adapt to an acidic condition, and 'acid adaptation' by maintaining integrity in the acidic condition. The other is a functional screening using the nonessential genes deletion collection of Saccharomyces cerevisiae. The expression analysis showed that genes involved in stress response, such as YGP1, TPS1 and HSP150, were induced under the acid shock response. Genes such as FIT2, ARN1 and ARN2, involved in metal metabolism regulated by Aft1p, were induced under the acid adaptation. AFT1 was induced under acid shock response and under acid adaptation with lactic acid. Moreover, green fluorescent protein-fused Aft1p was localized to the nucleus in cells grown in media containing lactic acid, acetic acid, or hydrochloric acid. Both analyses suggested that the acidic condition affects cell wall architecture. The depletion of cell-wall components encoded by SED1, DSE2, CTS1, EGT2, SCW11, SUN4 and YNL300W and histone acetyltransferase complex proteins encoded by YID21, EAF3, EAF5, EAF6 and YAF9 increased resistance to lactic acid. Depletion of the cell-wall mannoprotein Sed1p provided resistance to lactic acid, although the expression of SED1 was induced by exposure to lactic acid. Depletion of vacuolar membrane H+-ATPase and high-osmolarity glycerol mitogen-activated protein kinase proteins caused acid sensitivity. Moreover, our quantitative PCR showed that expression of PDR12 increased under acid shock response with lactic acid and decreased under acid adaptation with hydrochloric acid.

  3. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana.

    PubMed

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice

    2010-12-15

    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate.

  4. Effect of arachidonic and eicosapentaenoic acid metabolism on RAW 264.7 macrophage proliferation.

    PubMed

    Nieves, Diana; Moreno, Juan José

    2006-08-01

    Prostaglandins (PGs) and leukotrienes (LTs) derived from arachidonic acid (AA) are potent mediators of inflammation and cell proliferation. Dietary intake of eicosapentaenoic acid (EPA) appears beneficial to both inflammatory processes and cell proliferation. However, there is no clear mechanism explaining these effects. In this study, we investigated the effect of EPA on the AA incorporation in phospholipid membranes, on AA release and metabolism, and consequently, on PG synthesis. Our results showed not only that [(3)H]AA and [(14)C]EPA were similar incorporated into RAW 264.7 macrophage membranes, but also that the redistribution pattern between phospholipids was alike. [(3)H]AA or [(14)C]EPA release was induced by fetal bovine serum (FBS) in a similar fashion with AA metabolizing 3-fold more than EPA. In this way, we observed that AA could be metabolized by cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase (5-LOX) whereas EPA was metabolized by COX-2 and 5-LOX pathways. Moreover, both fatty acids were able to induce COX-2 expression. When we incubated [(3)H]AA labeled cells with exogenous EPA, we observed that EPA did not modify FBS-induced [(3)H]AA release but that the presence of EPA decreased [(3)H]AA metabolism and therefore PGE(2) synthesis. Moreover, we studied the effect of AA and EPA metabolites on macrophage proliferation. Our results showed that PGE(3) stimulated cell growth with a potency similar to that of PGE(2), whereas LTB(5) was less effective than LTB(4). These data suggest that the effects of EPA on cell growth might be attributable, at least in part, to the marked decrease of eicosanoid release.

  5. Defining meal requirements for protein to optimize metabolic roles of amino acids12345

    PubMed Central

    Anthony, Tracy G; Rasmussen, Blake B; Adams, Sean H; Lynch, Christopher J; Brinkworth, Grant D; Davis, Teresa A

    2015-01-01

    Dietary protein provides essential amino acids (EAAs) for the synthesis of new proteins plus an array of other metabolic functions; many of these functions are sensitive to postprandial plasma and intracellular amino acid concentrations. Recent research has focused on amino acids as metabolic signals that influence the rate of protein synthesis, inflammation responses, mitochondrial activity, and satiety, exerting their influence through signaling systems including mammalian/mechanistic target of rapamycin complex 1 (mTORC1), general control nonrepressed 2 (GCN2), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), serotonin, and insulin. These signals represent meal-based responses to dietary protein. The best characterized of these signals is the leucine-induced activation of mTORC1, which leads to the stimulation of skeletal muscle protein synthesis after ingestion of a meal that contains protein. The response of this metabolic pathway to dietary protein (i.e., meal threshold) declines with advancing age or reduced physical activity. Current dietary recommendations for protein are focused on total daily intake of 0.8 g/kg body weight, but new research suggests daily needs for older adults of ≥1.0 g/kg and identifies anabolic and metabolic benefits to consuming at least 20–30 g protein at a given meal. Resistance exercise appears to increase the efficiency of EAA use for muscle anabolism and to lower the meal threshold for stimulation of protein synthesis. Applying this information to a typical 3-meal-a-day dietary plan results in protein intakes that are well within the guidelines of the Dietary Reference Intakes for acceptable macronutrient intakes. The meal threshold concept for dietary protein emphasizes a need for redistribution of dietary protein for optimum metabolic health. PMID:25926513

  6. Defining meal requirements for protein to optimize metabolic roles of amino acids.

    PubMed

    Layman, Donald K; Anthony, Tracy G; Rasmussen, Blake B; Adams, Sean H; Lynch, Christopher J; Brinkworth, Grant D; Davis, Teresa A

    2015-04-29

    Dietary protein provides essential amino acids (EAAs) for the synthesis of new proteins plus an array of other metabolic functions; many of these functions are sensitive to postprandial plasma and intracellular amino acid concentrations. Recent research has focused on amino acids as metabolic signals that influence the rate of protein synthesis, inflammation responses, mitochondrial activity, and satiety, exerting their influence through signaling systems including mammalian/mechanistic target of rapamycin complex 1 (mTORC1), general control nonrepressed 2 (GCN2), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), serotonin, and insulin. These signals represent meal-based responses to dietary protein. The best characterized of these signals is the leucine-induced activation of mTORC1, which leads to the stimulation of skeletal muscle protein synthesis after ingestion of a meal that contains protein. The response of this metabolic pathway to dietary protein (i.e., meal threshold) declines with advancing age or reduced physical activity. Current dietary recommendations for protein are focused on total daily intake of 0.8 g/kg body weight, but new research suggests daily needs for older adults of ≥1.0 g/kg and identifies anabolic and metabolic benefits to consuming at least 20-30 g protein at a given meal. Resistance exercise appears to increase the efficiency of EAA use for muscle anabolism and to lower the meal threshold for stimulation of protein synthesis. Applying this information to a typical 3-meal-a-day dietary plan results in protein intakes that are well within the guidelines of the Dietary Reference Intakes for acceptable macronutrient intakes. The meal threshold concept for dietary protein emphasizes a need for redistribution of dietary protein for optimum metabolic health.

  7. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    PubMed Central

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors. PMID:24971025

  8. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork.

    PubMed

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors.

  9. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    PubMed

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  10. [Controlling arachidonic acid metabolic network: from single- to multi-target inhibitors of key enzymes].

    PubMed

    Liu, Ying; Chen, Zheng; Shang, Er-chang; Yang, Kun; Wei, Deng-guo; Zhou, Lu; Jiang, Xiao-lu; He, Chong; Lai, Lu-hua

    2009-03-01

    Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.

  11. Developmental pattern of 3-oxo-Δ4 bile acids in neonatal bile acid metabolism

    PubMed Central

    Inoue, T.; Kimura, A.; Aoki, K.; Tohma, M.; Kato, H.

    1997-01-01

    AIMS—To investigate whether a fetal pathway of bile acid synthesis persists in neonates and infants.
METHODS—3-oxo-Δ4 bile acids were determined qualitatively and quantitatively in the urine, meconium, and faeces of healthy neonates and infants, using gas chromatography-mass spectrometry.
RESULTS—The mean percentage of 3-oxo-Δ4 bile acids in total bile acids in urine at birth was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age. The concentration of this component in meconium was significantly higher than that in faeces at 7 days and at 1 or 3 months of age.
CONCLUSIONS—The presence of large amounts of urinary 3-oxo-Δ4 bile acids may indicate immaturity in the activity of hepatic 3-oxo-Δ4-steroid 5β-reductase in the first week of postnatal life. Large amounts of this component in meconium may be due to the ingestion of amniotic fluid by the fetus during pregnancy.

 Keywords: ketonic bile acid; 3-oxo-Δ4 bile acid; 3-oxo-Δ4-steroid 5β-reductase; meconium; gas chromatography-mass spectrometry PMID:9279184

  12. Dynamics of amino acid metabolism of primary human liver cells in 3D bioreactors

    PubMed Central

    Zeilinger, K.; Sickinger, S.; Schmidt-Heck, W.; Buentemeyer, H.; Iding, K.; Lehmann, J.; Pfaff, M.; Pless, G.; Gerlach, J.C.

    2006-01-01

    The kinetics of 18 amino acids, ammonia (NH3) and urea (UREA) in 18 liver cell bioreactor runs were analyzed and simulated by a two-compartment model consisting of a system of 42 differential equations. The model parameters, most of them representing enzymatic activities, were identified and their values discussed with respect to the different liver cell bioreactor performance levels. The nitrogen balance based model was used as a tool to quantify the variability of runs and to describe different kinetic patterns of the amino acid metabolism, in particular with respect to glutamate (GLU) and aspartate (ASP). PMID:16550345

  13. Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability.

    PubMed

    Patella, Francesca; Schug, Zachary T; Persi, Erez; Neilson, Lisa J; Erami, Zahra; Avanzato, Daniele; Maione, Federica; Hernandez-Fernaud, Juan R; Mackay, Gillian; Zheng, Liang; Reid, Steven; Frezza, Christian; Giraudo, Enrico; Fiorio Pla, Alessandra; Anderson, Kurt; Ruppin, Eytan; Gottlieb, Eyal; Zanivan, Sara

    2015-03-01

    Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability.

  14. Oleic acid in olive oil: from a metabolic framework toward a clinical perspective.

    PubMed

    Bermudez, Beatriz; Lopez, Sergio; Ortega, Almudena; Varela, Lourdes M; Pacheco, Yolanda M; Abia, Rocio; Muriana, Francisco J G

    2011-01-01

    Traditionally, nutrients such as fatty acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, accumulating data from multiple lines of evidence suggest that dietary fatty acids are linked not only to health promotion but also to disease pathogenesis. Metabolism in humans is regulated by complex hormonal signals and substrate interactions. For many years, the clinical focus has centered on a wide metabolic picture after an overnight fast. Nonetheless, the postprandial state (i.e., "the period that comprises and follows a meal") is an important one, and silent disturbances in this period are involved in the genesis of numerous pathological conditions, including atherosclerosis. In this review article, we present an overview of the evidence demonstrating the relevance of oleic acid in olive oil on different nutrition-related issues. We also discuss the impact of oleic acid in olive oil and its clinical relevance to major risk factors for cardiovascular disease in the context of the postprandial state and with regard to other dietary fatty acids.

  15. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression.

    PubMed

    Mocking, Roel J T; Ruhé, Henricus G; Assies, Johanna; Lok, Anja; Koeter, Maarten W J; Visser, Ieke; Bockting, Claudi L H; Schene, Aart H

    2013-09-01

    Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity and fatty acid (FA)-metabolism have been observed in (recurrent) major depressive disorder (MDD). Through the pathophysiological roles of FAs in the brain and cardiovascular system, a hypothesized relationship between HPA-axis activity and FA-metabolism could form a possible missing link accounting for the association of HPA-axis hyperactivity with recurrence and cardiovascular disease in MDD. In 137 recurrent MDD-patients and 73 age- and sex-matched controls, we therefore investigated associations between salivary cortisol (morning and evening) and the following indicators of FA-metabolism measured in the red blood cell membrane: (I) three main FAs [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)], and (II) structural FA indices (unsaturation, chain length, peroxidation) calculated from concentrations of 29 FAs to delineate overall FA-characteristics. In addition, we compared these associations in patients with those in controls. In patients, evening cortisol concentrations were significantly negatively associated with DHA (B=-1.358; SE=0.499; t=-2.72; p=.006), the unsaturation index (B=-0.021; SE=0.009; t=-2.42; p=.018), chain length index (B=-0.060; SE=0.025; t=-2.41; p=.019), and peroxidation index (B=-0.029; SE=0.012; t=-2.48; p=.015). The relations between cortisol and the latter three variables were significantly negative in patients relative to controls. Significance remained after correction for confounders. Our results suggest a relationship between HPA-axis activity and FA-metabolism in recurrent MDD. Future randomized experimental intervention studies using clinical outcome measures could help to further elucidate the suggested effects of hypercortisolemia in the brain and cardiovascular system in recurrent MDD.

  16. Fatty Acid Metabolism and Ketogenesis in the Rat Exposed to Streptococcus pneumoniae.

    DTIC Science & Technology

    1980-04-30

    supplementation during infectious illness, these data suggest that carnitine supplementation would have no protein sparing effect during infection...If necessary end Identify by block number) Fatty acid metabolism, ketogenesis, carnitine , coenzymeA Am~ AT ~en80 5 22 01S 20. 9SrA~r(Cerdlus 10 0~0...control sites of hepatic ketogenesis, including hepatic concentrations * of coenzyme A, carnitine and malonyl-coenzyme A.. These studies show that dun

  17. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production.

    PubMed

    Michelucci, Alessandro; Cordes, Thekla; Ghelfi, Jenny; Pailot, Arnaud; Reiling, Norbert; Goldmann, Oliver; Binz, Tina; Wegner, André; Tallam, Aravind; Rausell, Antonio; Buttini, Manuel; Linster, Carole L; Medina, Eva; Balling, Rudi; Hiller, Karsten

    2013-05-07

    Immunoresponsive gene 1 (Irg1) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis-aconitate, a tricarboxylic acid cycle intermediate. Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect. We purified IRG1 protein and identified its cis-aconitate decarboxylating activity in an enzymatic assay. Itaconic acid is an organic compound that inhibits isocitrate lyase, the key enzyme of the glyoxylate shunt, a pathway essential for bacterial growth under specific conditions. Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis. Furthermore, Irg1 gene silencing in macrophages resulted in significantly decreased intracellular itaconic acid levels as well as significantly reduced antimicrobial activity during bacterial infections. Taken together, our results demonstrate that IRG1 links cellular metabolism with immune defense by catalyzing itaconic acid production.

  18. Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge.

    PubMed

    Cho, Joo-Youn; Matsubara, Tsutomu; Kang, Dong Wook; Ahn, Sung-Hoon; Krausz, Kristopher W; Idle, Jeffrey R; Luecke, Hans; Gonzalez, Frank J

    2010-05-01

    Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.

  19. Analysis of Growth Inhibition and Metabolism of Hydroxycinnamic Acids by Brewing and Spoilage Strains of Brettanomyces Yeast.

    PubMed

    Lentz, Michael; Harris, Chad

    2015-10-15

    Brettanomyces yeasts are well-known as spoilage organisms in both the wine and beer industries, but also contribute important desirable characters to certain beer styles. These properties are mediated in large part by Brettanomyces' metabolism of hydroxycinnamic acids (HCAs) present in beverage raw materials. Here we compare growth inhibition by, and metabolism of, HCAs among commercial brewing strains and spoilage strains of B. bruxellensis and B. anomalus. These properties vary widely among the different strains tested and between the HCAs analyzed. Brewing strains showed more efficient metabolism of ferulic acid over p-coumaric acid, a trait not shared among the spoilage strains.

  20. Analysis of Growth Inhibition and Metabolism of Hydroxycinnamic Acids by Brewing and Spoilage Strains of Brettanomyces Yeast

    PubMed Central

    Lentz, Michael; Harris, Chad

    2015-01-01

    Brettanomyces yeasts are well-known as spoilage organisms in both the wine and beer industries, but also contribute important desirable characters to certain beer styles. These properties are mediated in large part by Brettanomyces’ metabolism of hydroxycinnamic acids (HCAs) present in beverage raw materials. Here we compare growth inhibition by, and metabolism of, HCAs among commercial brewing strains and spoilage strains of B. bruxellensis and B. anomalus. These properties vary widely among the different strains tested and between the HCAs analyzed. Brewing strains showed more efficient metabolism of ferulic acid over p-coumaric acid, a trait not shared among the spoilage strains. PMID:28231223

  1. Amino acid metabolism by perfused rat hindquarter. Effects of insulin, leucine and 2-chloro-4-methylvalerate.

    PubMed Central

    Davis, E J; Lee, S H

    1985-01-01

    Hindquarters from starved rats were perfused without substrates but in the presence of an O2- and CO2-carrying perfluorocarbon emulsion to evaluate principally the metabolism of individual endogenous and protein-derived amino acids by this muscle preparation. This experimental model was shown, by a battery of metabolite measurements, to maintain cellular homoeostasis for at least 2h. The net appearance of most amino acids closely approximated their frequency of occurrence in muscle proteins, showing that they are not significantly metabolized. Exceptions were the branched-chain amino acids, methionine and those amino acids that are interconvertible with intermediates of the citrate cycle and pyruvate through coupled transaminations. The evidence indicates that only valine, isoleucine, aspartate and probably methionine can be catabolized by skeletal muscle to provide carbon precursors for glutamate/glutamine and alanine that are formed de novo by protein-catabolic muscle. The protein-sparing effects of insulin and leucine were confirmed. Although each decreased proteolysis and the net appearance of free amino acids, they were generally without effect on the ratios of amino acids formed. 2-Chloro-4-methylvalerate selectively stimulated the removal rate for the branched-chain amino acids, confirming the idea that the branched-chain oxo acid dehydrogenase normally limits the rate of their oxidation by muscle. It is also concluded that, since alanine was not formed in excess of that found in muscle proteins when no glucose was added as substrate, the excess of alanine (carbon) released from muscles in other studies is derived to a large extent, but not exclusively, from preformed carbohydrate. PMID:3899101

  2. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    PubMed

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  3. Metabolic Effects of Cholecystectomy: Gallbladder Ablation Increases Basal Metabolic Rate through G-Protein Coupled Bile Acid Receptor Gpbar1-Dependent Mechanisms in Mice

    PubMed Central

    Cortés, Víctor; Amigo, Ludwig; Zanlungo, Silvana; Galgani, José; Robledo, Fermín; Arrese, Marco; Bozinovic, Francisco; Nervi, Flavio

    2015-01-01

    Background & Aims Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor Gpbar1/TGR5 by cAMP-dependent mechanisms. Cholecystectomy (XGB) increases BAs recirculation rates resulting in increased tissue exposure to BAs during the light phase of the diurnal cycle in mice. We aimed to determine: 1) the effects of XGB on basal metabolic rate (BMR) and 2) the roles of TGR5 on XGB-dependent changes in BMR. Methods BMR was determined by indirect calorimetry in wild type and Tgr5 deficient (Tgr5-/-) male mice. Bile flow and BAs secretion rates were measured by surgical diversion of biliary duct. Biliary BAs and cholesterol were quantified by enzymatic methods. BAs serum concentration and specific composition was determined by liquid chromatography/tandem mass spectrometry. Gene expression was determined by qPCR analysis. Results XGB increased biliary BAs and cholesterol secretion rates, and elevated serum BAs concentration in wild type and Tgr5-/- mice during the light phase of the diurnal cycle. BMR was ~25% higher in cholecystectomized wild type mice (p <0.02), whereas no changes were detected in cholecystectomized Tgr5-/- mice compared to wild-type animals. Conclusion XGB increases BMR by TGR5-dependent mechanisms in mice. PMID:25738495

  4. Metabolic flux analysis of Escherichia coli MG1655 under octanoic acid (C8) stress.

    PubMed

    Fu, Yanfen; Yoon, Jong Moon; Jarboe, Laura; Shanks, Jacqueline V

    2015-05-01

    Systems metabolic engineering has made the renewable production of industrial chemicals a feasible alternative to modern operations. One major example of a renewable process is the production of carboxylic acids, such as octanoic acid (C8), from Escherichia coli, engineered to express thioesterase enzymes. C8, however, is toxic to E. coli above a certain concentration, which limits the final titer. (13)C metabolic flux analysis of E. coli was performed for both C8 stress and control conditions using NMR2Flux with isotopomer balancing. A mixture of labeled and unlabeled glucose was used as the sole carbon source for bacterial growth for (13)C flux analysis. By comparing the metabolic flux maps of the control condition and C8 stress condition, pathways that were altered under the stress condition were identified. C8 stress was found to reduce carbon flux in several pathways: the tricarboxylic acid (TCA) cycle, the CO2 production, and the pyruvate dehydrogenase pathway. Meanwhile, a few pathways became more active: the pyruvate oxidative pathway, and the extracellular acetate production. These results were statistically significant for three biological replicates between the control condition and C8 stress. As a working hypothesis, the following causes are proposed to be the main causes for growth inhibition and flux alteration for a cell under stress: membrane disruption, low activity of electron transport chain, and the activation of the pyruvate dehydrogenase regulator (PdhR).

  5. Contrasting metabolic effects of medium- versus long-chain fatty acids in skeletal muscle[S

    PubMed Central

    Montgomery, Magdalene K.; Osborne, Brenna; Brown, Simon H. J.; Small, Lewin; Mitchell, Todd W.; Cooney, Gregory J.; Turner, Nigel

    2013-01-01

    Dietary intake of long-chain fatty acids (LCFAs) plays a causative role in insulin resistance and risk of diabetes. Whereas LCFAs promote lipid accumulation and insulin resistance, diets rich in medium-chain fatty acids (MCFAs) have been associated with increased oxidative metabolism and reduced adiposity, with few deleterious effects on insulin action. The molecular mechanisms underlying these differences between dietary fat subtypes are poorly understood. To investigate this further, we treated C2C12 myotubes with various LCFAs (16:0, 18:1n9, and 18:2n6) and MCFAs (10:0 and 12:0), as well as fed mice diets rich in LCFAs or MCFAs, and investigated fatty acid-induced changes in mitochondrial metabolism and oxidative stress. MCFA-treated cells displayed less lipid accumulation, increased mitochondrial oxidative capacity, and less oxidative stress than LCFA-treated cells. These changes were associated with improved insulin action in MCFA-treated myotubes. MCFA-fed mice exhibited increased energy expenditure, reduced adiposity, and better glucose tolerance compared with LCFA-fed mice. Dietary MCFAs increased respiration in isolated mitochondria, with a simultaneous reduction in reactive oxygen species generation, and subsequently low oxidative damage. Collectively our findings indicate that in contrast to LCFAs, MCFAs increase the intrinsic respiratory capacity of mitochondria without increasing oxidative stress. These effects potentially contribute to the beneficial metabolic actions of dietary MCFAs. PMID:24078708

  6. Sulfur amino acid metabolism limits the growth of children living in environments of poor sanitation.

    PubMed

    Bickler, Stephen W; Ring, Jason; De Maio, Antonio

    2011-09-01

    Environmental enteropathy has been identified as a cause of poor growth in children living in low-income countries, but a mechanism has not been well defined. We suggest changes in sulfur amino acid metabolism can in part explain the poor growth and possibly the histological changes in the small bowel, which is the hallmark of environmental enteropathy. In environments of poor sanitation, where infection is common, we propose increased oxidative stress drives methionine metabolism toward cystathionine synthesis. This "cystathionine siphon" limits sulfur amino acids from participating in critical protein synthesis pathways. Increased expression of cystathionine β-synthase (CBS) could be one mechanism, as lipopolysaccharide and TNFα increase activity of this enzyme in vivo. CBS catalyzes the first of two steps in the transsulfuration pathway that converts homocysteine to cysteine. As enterocytes are one of the most rapidly proliferating cells in the body, we suggest diminished translation might also be important in the barrier failure observed in environmental enteropathy. Identifying sulfur amino acid metabolism as a mechanism leading to poor growth provides a new testable hypothesis for the undernutrition observed in children living in settings of poor sanitation.

  7. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    PubMed Central

    Todorčević, Marijana; Hodson, Leanne

    2015-01-01

    Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182

  8. Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men

    PubMed Central

    Blondin, Denis P.; Tingelstad, Hans C.; Noll, Christophe; Frisch, Frédérique; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric E; Richard, Denis; Haman, François; Carpentier, André C.

    2017-01-01

    In rodents, brown adipose tissue (BAT) plays an important role in producing heat to defend against the cold and can metabolize large amounts of dietary fatty acids (DFA). The role of BAT in DFA metabolism in humans is unknown. Here we show that mild cold stimulation (18 °C) results in a significantly greater fractional DFA extraction by BAT relative to skeletal muscle and white adipose tissue in non-cold-acclimated men given a standard liquid meal containing the long-chain fatty acid PET tracer, 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid (18FTHA). However, the net contribution of BAT to systemic DFA clearance is comparatively small. Despite a 4-week cold acclimation increasing BAT oxidative metabolism 2.6-fold, BAT DFA uptake does not increase further. These findings show that cold-stimulated BAT can contribute to the clearance of DFA from circulation but its contribution is not as significant as the heart, liver, skeletal muscles or white adipose tissues. PMID:28134339

  9. Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons

    PubMed Central

    Kang, Kyungtae; Joo, Sunghoon; Choi, Ji Yu; Geum, Sujeong; Hong, Seok-Pyo; Lee, Seung-Yeul; Kim, Yong Ho; Kim, Seong-Min; Yoon, Myung-Han; Nam, Yoonkey; Lee, Kyung-Bok; Lee, Hee-Yoon; Choi, Insung S.

    2015-01-01

    The posttranslational modification of neural cell-adhesion molecule (NCAM) with polysialic acid (PSA) and the spatiotemporal distribution of PSA-NCAM play an important role in the neuronal development. In this work, we developed a tissue-based strategy for metabolically incorporating an unnatural monosaccharide, peracetylated N-azidoacetyl-d-mannosamine, in the sialic acid biochemical pathway to present N-azidoacetyl sialic acid to PSA-NCAM. Although significant neurotoxicity was observed in the conventional metabolic labeling that used the dissociated neuron cells, neurotoxicity disappeared in this modified strategy, allowing for investigation of the temporal and spatial distributions of PSA in the primary hippocampal neurons. PSA-NCAM was synthesized and recycled continuously during neuronal development, and the two-color labeling showed that newly synthesized PSA-NCAMs were transported and inserted mainly to the growing neurites and not significantly to the cell body. This report suggests a reliable and cytocompatible method for in vitro analysis of glycans complementary to the conventional cell-based metabolic labeling for chemical glycobiology. PMID:25564666

  10. Effects of bioactive fatty acid amide derivatives in zebrafish scale model of bone metabolism and disease.

    PubMed

    Carnovali, M; Ottria, R; Pasqualetti, S; Banfi, G; Ciuffreda, P; Mariotti, M

    2016-02-01

    The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

  11. Aspartic acid concentrations in coral skeletons as recorders of past disturbances of metabolic rates

    NASA Astrophysics Data System (ADS)

    Gupta, Lallan P.; Suzuki, Atsushi; Kawahata, Hodaka

    2006-11-01

    The composition of total hydrolysable amino acids (THAAs) in a skeleton of the coral Porites australiensis, collected from Ishigaki Island, Japan, was examined in order to determine whether amino acids (AA) can be used as biomarkers of past changes in coral physiology (metabolism). Micro-samples, corresponding to a time resolution of 1 month, were collected along the growth axis of the coral. Of the 20 AAs analyzed, aspartic acid (Asp) was the most abundant, and its mole concentration relative to the sum of all other AAs (mole%Asp) showed a clear seasonal pattern of low content during winters and high during summers. A growth disturbance in the coral skeleton during 1988 1990, shown by X-ray scans and oxygen and carbon stable isotope data, was marked by a high mole%Asp ratio. Variability in carbon isotope data has often been attributed to metabolic effects, or changes in the isotopic composition of seawater, or both. The changes in mole%Asp shown here suggest that metabolic effects are mainly responsible for sharp changes in carbon isotope profiles during periods of growth disturbance.

  12. Phase I Metabolic Stability and Electrophilic Reactivity of 2-Phenylaminophenylacetic Acid Derived Compounds.

    PubMed

    Pang, Yi Yun; Tan, Yee Min; Chan, Eric Chun Yong; Ho, Han Kiat

    2016-07-18

    Diclofenac and lumiracoxib are two highly analogous 2-phenylaminophenylacetic acid anti-inflammatory drugs exhibiting occasional dose-limiting hepatotoxicities. Prior data indicate that bioactivation and reactive metabolite formation play roles in the observed toxicity, but the exact chemical influence of the substituents remains elusive. In order to elucidate the role of chemical influence on metabolism related toxicity, metabolic stability and electrophilic reactivity were investigated for a series of structurally related analogues and their resulting metabolites. The resulting analogues embody progressive physiochemical changes through varying halogeno- and aliphatic substituents at two positions and were subjected to in vitro human liver microsomal metabolic stability and cell-based GSH depletion assays (to measure electrophilic reactivity). LC-MS/MS analysis of the GSH trapped reactive intermediates derived from the analogues was then used to identify the putative structures of reactive metabolites. We found that chemical modifications of the structural backbone led to noticeable perturbations of metabolic stability, electrophilic reactivity, and structures and composition of reactive metabolites. With the acquired data, the relationships between stability, reactivity, and toxicity were investigated in an attempt to correlate between Phase I metabolism and in vitro toxicity. A positive correlation was identified between reactivity and in vitro toxicity, indicating that electrophilic reactivity can be an indicator for in vitro toxicity. All in all, the effect of substituents on the structures and reactivity of the metabolites, however subtle the changes, should be taken into consideration during future drug design involving similar chemical features.

  13. Opportunities for probiotics and polyunsaturated fatty acids to improve metabolic health of overweight pregnant women.

    PubMed

    Mokkala, K; Röytiö, H; Ekblad, U; Laitinen, K

    2017-02-07

    Overweight during pregnancy predisposes both the mother and foetus to health complications. Maternal complications include gestational diabetes, obstetric problems and type 2 diabetes later in life. Complications for the offspring are not only restricted to the foetal period or birth, such as prematurity and foetal macrosomia, but may also have long-term metabolic health implications through the mechanism of early nutrition programming. One of the key metabolic components characterising overweight in the non-pregnant state is low-grade inflammation manifested by elevated levels of circulatory pro-inflammatory cytokines. In pregnancy, in addition to adipose tissue and placenta, inflammatory response may originate from the gut. The extent to which overweight induces metabolic maladaptation during pregnancy and further compromises maternal and child health is currently poorly understood. In this review, we evaluate recent scientific literature and describe the suggested links between overweight, gut and low-grade inflammation associated metabolic disorders. We focus on overweight pregnant women and gestational diabetes, and discuss how specific dietary factors, probiotics and long-chain polyunsaturated fatty acids (fish oil), might confer health benefits in combatting against metabolic risk factors.

  14. Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

    PubMed Central

    Ljungdahl, Per O.; Daignan-Fornier, Bertrand

    2012-01-01

    Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear. PMID:22419079

  15. Proline Coordination with Fatty Acid Synthesis and Redox Metabolism of Chloroplast and Mitochondria1[OPEN

    PubMed Central

    Shinde, Suhas; Villamor, Joji Grace; Lin, Wendar; Verslues, Paul E.

    2016-01-01

    Proline (Pro) accumulation is one of the most prominent changes in plant metabolism during drought and low water potential; however, the regulation and function of Pro metabolism remain unclear. We used a combination of forward genetic screening based on a Proline Dehydrogenase1 (PDH1) promoter-luciferase reporter (PDH1pro:LUC2) and RNA sequencing of the Pro synthesis mutant p5cs1-4 to identify multiple loci affecting Pro accumulation in Arabidopsis (Arabidopsis thaliana). Two mutants having high PDH1pro:LUC2 expression and increased Pro accumulation at low water potential were found to be alleles of Cytochrome P450, Family 86, Subfamily A, Polypeptide2 (CYP86A2) and Long Chain Acyl Synthetase2 (LACS2), which catalyze two successive steps in very-long-chain fatty acid (VLCFA) synthesis. Reverse genetic experiments found additional VLCFA and lipid metabolism-related mutants with increased Pro accumulation. Altered cellular redox status is a key factor in the coordination of Pro and VLCFA metabolism. The NADPH oxidase inhibitor diphenyleneiodonium (DPI) induced high levels of Pro accumulation and strongly repressed PDH1pro:LUC2 expression. cyp86a2 and lacs2 mutants were hypersensitive to diphenyleneiodonium but could be reverted to wild-type Pro and PDH1pro:LUC2 expression by reactive oxygen species scavengers. The coordination of Pro and redox metabolism also was indicated by the altered expression of chloroplast and mitochondria electron transport genes in p5cs1-4. These results show that Pro metabolism is both influenced by and influences cellular redox status via previously unknown coordination with several metabolic pathways. In particular, Pro and VLCFA synthesis share dual roles to help buffer cellular redox status while producing products useful for stress resistance, namely the compatible solute Pro and cuticle lipids. PMID:27512016

  16. G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice.

    PubMed

    Donepudi, Ajay C; Boehme, Shannon; Li, Feng; Chiang, John Y L

    2017-03-01

    Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G-protein-coupled receptor (Takeda G-protein-coupled receptor 5; Tgr5). The role of FXR in regulation of bile acid synthesis and hepatic metabolism has been studied extensively. However, the role of TGR5 in hepatic metabolism has not been explored. The liver plays a central role in lipid metabolism, and impaired response to fasting and feeding contributes to steatosis and nonalcoholic fatty liver and obesity. We have performed a detailed analysis of gallbladder bile acid and lipid metabolism in Tgr5(-/-) mice in both free-fed and fasted conditions. Lipid profiles of serum, liver and adipose tissues, bile acid composition, energy metabolism, and messenger RNA and protein expression of the genes involved in lipid metabolism were analyzed. Results showed that deficiency of the Tgr5 gene in mice alleviated fasting-induced hepatic lipid accumulation. Expression of liver oxysterol 7α-hydroxylase in the alternative bile acid synthesis pathway was reduced. Analysis of gallbladder bile acid composition showed marked increase of taurocholic acid and decrease of tauro-α and β-muricholic acid in Tgr5(-/-) mice. Tgr5(-/-) mice had increased hepatic fatty acid oxidation rate and decreased hepatic fatty acid uptake. Interestingly, fasting induction of fibroblast growth factor 21 in liver was attenuated. In addition, fasted Tgr5(-/-) mice had increased activation of hepatic growth hormone-signal transducer and activator of transcription 5 (GH-Stat5) signaling compared to wild-type mice.

  17. Systematic identification of genes involved in metabolic acid stress resistance in yeast and their potential as cancer targets

    PubMed Central

    Shin, John J.; Aftab, Qurratulain; Austin, Pamela; McQueen, Jennifer A.; Poon, Tak; Li, Shu Chen; Young, Barry P.; Roskelley, Calvin D.

    2016-01-01

    ABSTRACT A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV), mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln) amidotransferase complex], histone methylation (Set1C–COMPASS), lysosome biogenesis (AP-3 adapter complex), and mRNA processing and P-body formation (PAN complex). We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial

  18. Lipid and fatty acid metabolism in Ralstonia eutropha: relevance for the biotechnological production of value-added products.

    PubMed

    Riedel, Sebastian L; Lu, Jingnan; Stahl, Ulf; Brigham, Christopher J

    2014-02-01

    Lipid and fatty acid metabolism has been well studied in model microbial organisms like Escherichia coli and Bacillus subtilis. The major precursor of fatty acid biosynthesis is also the major product of fatty acid degradation (β-oxidation), acetyl-CoA, which is a key metabolite for all organisms. Controlling carbon flux to fatty acid biosynthesis and from β-oxidation allows for the biosynthesis of natural products of biotechnological importance. Ralstonia eutropha can utilize acetyl-CoA from fatty acid metabolism to produce intracellular polyhydroxyalkanoate (PHA). R. eutropha can also be engineered to utilize fatty acid metabolism intermediates to produce different PHA precursors. Metabolism of lipids and fatty acids can be rerouted to convert carbon into other value-added compounds like biofuels. This review discusses the lipid and fatty acid metabolic pathways in R. eutropha and how they can be used to construct reagents for the biosynthesis of products of industrial importance. Specifically, how the use of lipids or fatty acids as the sole carbon source in R. eutropha cultures adds value to these biotechnological products will be discussed here.

  19. Impact of combined resistance and aerobic exercise training on branched-chain amino acid turnover, glycine metabolism and insulin sensitivity in overweight humans

    PubMed Central

    Glynn, Erin L.; Piner, Lucy W.; Huffman, Kim M.; Slentz, Cris A.; Elliot-Penry, Lorraine; AbouAssi, Hiba; White, Phillip J.; Bain, James R.; Muehlbauer, Michael J.; Ilkayeva, Olga R.; Stevens, Robert D.; Porter Starr, Kathryn N.; Bales, Connie W.; Volpi, Elena; Brosnan, M. Julia; Trimmer, Jeff K.; Rolph, Timothy P.

    2016-01-01

    Aims/hypotheses Obesity is associated with decreased insulin sensitivity (IS) and elevated plasma branched-chain amino acids (BCAAs). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight (OW) individuals during exercise intervention. Methods Whole-body leucine turnover, IS by hyperinsulinaemic–euglycaemic clamp, and circulating and skeletal muscle amino acids, branched-chain α-keto acids and acylcarnitines were measured in ten healthy controls (Control) and nine OW, untrained, insulin-resistant individuals (OW-Untrained). OW-Untrained then underwent a 6 month aerobic and resistance exercise programme and repeated testing (OW-Trained). Results IS was higher in Control vs OW-Untrained and increased significantly following exercise. IS was lower in OW-Trained vs Control expressed relative to body mass, but was not different from Control when normalised to fat-free mass (FFM). Plasma BCAAs and leucine turnover (relative to FFM) were higher in OW-Untrained vs Control, but did not change on average with exercise. Despite this, within individuals, the decrease in molar sum of circulating BCAAs was the best metabolic predictor of improvement in IS. Circulating glycine levels were higher in Control and OW-Trained vs OW-Untrained, and urinary metabolic profiling suggests that exercise induces more efficient elimination of excess acyl groups derived from BCAA and aromatic amino acid (AA) metabolism via formation of urinary glycine adducts. Conclusions/interpretation A mechanism involving more efficient elimination of excess acyl groups derived from BCAA and aromatic AA metabolism via glycine conjugation in the liver, rather than increased BCAA disposal through oxidation and turnover, may mediate interactions between exercise, BCAA metabolism and IS. Trial registration Clinicaltrials.gov NCT01786941 PMID:26254576

  20. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    SciTech Connect

    Liu, Jie; Lu, Yuan-Fu; Zhang, Youcai; Wu, Kai Connie; Fan, Fang; Klaassen, Curtis D.

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  1. Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population.

    PubMed

    Tang, Shanshan; Zhang, Rong; Jiang, Feng; Wang, Jie; Chen, Miao; Peng, Danfeng; Yan, Jing; Wang, Shiyun; Bao, Yuqian; Hu, Cheng; Jia, Weiping

    2015-06-26

    Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with NGT, 63 subjects with IGR and 72 subjects with new-onset T2DM. Circulating irisin levels were measured by ELISA. Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups (p=0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol (p=0.0005), low-density lipoprotein cholesterol (p=0.0014), fasting fatty acids (p=0.0402) and uric acid (p=0.0062). By dividing the serum irisin levels into three tertile group, the values of total cholesterol, low-density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin (p<0.05) . Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population. This article is protected by copyright. All rights reserved.

  2. Metabolism in humans of cis-12,trans-15-octadecadienoic acid relative to palmitic, stearic, oleic and linoleic acids

    SciTech Connect

    Emken, E.A.; Rohwedder, W.K.; Adlof, R.O.; Rakoff, H.; Gulley, R.M.

    1987-07-01

    Mixtures of triglycerides containing deuterium-labeled hexadecanoic acid (16:0), octadecanoic acid (18:0), cis-9-octadecenoic acid (9c-18:1), cis-9,cis-12-octadecadienoic acid (9c, 12c-18:2) and cis-12,trans-15-octadecadienoic acid (12c,15t-18:2) were fed to two young-adult males. Plasma lipid classes were isolated from samples collected periodically over 48 hr. Incorporation and turnover of the deuterium-labeled fats in plasma lipids were followed by gas chromatography-mass spectrometry (GC-MS) analysis of the methyl ester derivatives. Absorption of the deuterated fats was followed by GC-MS analysis of chylomicron triglycerides isolated by ultracentrifugation. Results were the following: (i) endogenous fat contributed about 40% of the total fat incorporated into chylomicron triglycerides; (ii) elongation, desaturation and chain-shortened products from the deuterated fats were not detected; (iii) the polyunsaturated isomer 12c,15t-18:2 was metabolically more similar to saturated and 9c-18:1 fatty acids than to 9c,12c-18:2; (iv) relative incorporation of 9c,12c-18:2 into phospholipids did not increase proportionally with an increase of 9c,12c-18:2 in the mixture of deuterated fats fed; (v) absorption of 16:0, 18:0, 9c-18:1, 9c,12c-18:2 and 12c,15t-18:2 were similar; and (vi) data for the 1- and 2-acyl positions of phosphatidylcholine and for cholesteryl ester fractions reflected the known high specificity of phosphatidylcholine acyltransferase and lecithin:cholesteryl acyltransferase for 9c,12c-18:2. These results illustrate that incorporation of dietary fatty acids into human plasma lipid classes is selectively controlled and that incorporation of dietary 9c,12c-18:2 is limited.

  3. Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120.

    PubMed

    Ulven, Trond; Christiansen, Elisabeth

    2015-01-01

    It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides acting as precursors of potent signaling molecules, dietary fatty acids act directly on intracellular and cell surface receptors. The free fatty acid receptor 4 (FFA4, previously GPR120) is linked to the regulation of body weight, inflammation, and insulin resistance and represents a potential target for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also discuss the possibility of dietary schemes that implement activation of FFA4.

  4. The Effects of Lowering Uric Acid Levels Using Allopurinol on Components of Metabolic Syndrome

    PubMed Central

    Heimbach, Esther J.; Bowden, Rodney G.; Griggs, Jackson O.; Beaujean, A. Alexander; Doyle, Eva I.; Doyle, Robert D.

    2012-01-01

    Background Researchers have reported an independent direct relationship between lipid levels and hyperuricemia with MetS. The purpose of this study was to determine the relationship between serum uric acid levels and lipids among patients on allopurinol. Methods A retrospective secondary data analysis was conducted on 66 adult patients from a family health clinic in Central Texas. Medical records used were recorded during a nine year period (2002 - 2010) ascertaining the relationship between uric acid and lipids. Results Spearman correlations revealed a weak correlation between uric acid and total cholesterol, a weak correlation between uric acid and triglycerides and LDL-C. A weak inverse correlation was discovered between uric acid and HDL-C. A moderate correlation was discovered when all lipid variables combined were compared to uric acid. Conclusions We discovered LDL-C and triglycerides to be significant predictors of uric acid with weak correlations. Additionally, weak correlations existed between uric acid and total cholesterol and HDL-C with an inverse relationship discovered with HDL-C. These findings support the literature suggesting that uric acid is more likely to be associated with total cholesterol and triglycerides. In addition, new discoveries serve as an indication that LDL-C may also be associated with uric acids levels. The mechanism by which uric acid may regulate lipids is elusive but suggestions have included suppression of lipid peroxidase and decreases in critical lipase activity.

  5. Yhhu981, a novel compound, stimulates fatty acid oxidation via the activation of AMPK and ameliorates lipid metabolism disorder in ob/ob mice

    PubMed Central

    Zeng, Hong-liang; Huang, Su-ling; Xie, Fu-chun; Zeng, Li-min; Hu, You-hong; Leng, Ying

    2015-01-01

    Aim: Defects in fatty acid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fatty acid metabolism in vitro and in vivo. Methods: The capacity to stimulate fatty acid oxidation was assessed in C2C12 myotubes. The fatty acid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg·kg−1·d−1 for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5–25 μmol/L) significantly increased fatty acid oxidation and the expression of related genes (Sirt1, Pgc1α and Mcad) in C2C12 myotubes, and inhibited fatty acid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fatty acid oxidation in yhhu981-treated C2C12 myotubes and fatty acid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fatty acid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. PMID:25732571

  6. Modulation of tissue fatty acids by L-carnitine attenuates metabolic syndrome in diet-induced obese rats.

    PubMed

    Panchal, Sunil K; Poudyal, Hemant; Ward, Leigh C; Waanders, Jennifer; Brown, Lindsay

    2015-08-01

    Obesity and dyslipidaemia are metabolic defects resulting from impaired lipid metabolism. These impairments are associated with the development of cardiovascular disease and non-alcoholic fatty liver disease. Correcting the defects in lipid metabolism may attenuate obesity and dyslipidaemia, and reduce cardiovascular risk and liver damage. L-Carnitine supplementation was used in this study to enhance fatty acid oxidation so as to ameliorate diet-induced disturbances in lipid metabolism. Male Wistar rats (8-9 weeks old) were fed with either corn starch or high-carbohydrate, high-fat diets for 16 weeks. Separate groups were supplemented with L-carnitine (1.2% in food) on either diet for the last 8 weeks of the protocol. High-carbohydrate, high-fat diet-fed rats showed central obesity, dyslipidaemia, hypertension, impaired glucose tolerance, hyperinsulinaemia, cardiovascular remodelling and non-alcoholic fatty liver disease. L-Carnitine supplementation attenuated these high-carbohydrate, high-fat diet-induced changes, together with modifications in lipid metabolism including the inhibition of stearoyl-CoA desaturase-1 activity, reduced storage of short-chain monounsaturated fatty acids in the tissues with decreased linoleic acid content and trans fatty acids stored in retroperitoneal fat. Thus, L-carnitine supplementation attenuated the signs of metabolic syndrome through inhibition of stearoyl-CoA desaturase-1 activity, preferential β-oxidation of some fatty acids and increased storage of saturated fatty acids and relatively inert oleic acid in the tissues.

  7. Invited review: palmitic and stearic acid metabolism in lactating dairy cows.

    PubMed

    Loften, J R; Linn, J G; Drackley, J K; Jenkins, T C; Soderholm, C G; Kertz, A F

    2014-01-01

    Energy is the most limiting nutritional component in diets for high-producing dairy cows. Palmitic (C16:0) and stearic (C18:0) acids have unique and specific functions in lactating dairy cows beyond a ubiquitous energy source. This review delineates their metabolism and usage in lactating dairy cows from diet to milk production. Palmitic acid is the fatty acid (FA) found in the greatest quantity in milk fat. Dietary sources of C16:0 generally increase milk fat yield and are used as an energy source for milk production and replenishing body weight loss during periods of negative energy balance. Stearic acid is the most abundant FA available to the dairy cow and is used to a greater extent for milk production and energy balance than C16:0. However, C18:0 is also intimately involved in milk fat production. Quantifying the transfer of each FA from diet into milk fat is complicated by de novo synthesis of C16:0 and desaturation of C18:0 to oleic acid in the mammary gland. In addition, incorporation of both FA into milk fat appears to be limited by the cow's requirement to maintain fluidity of milk, which requires a balance between saturated and unsaturated FA. Oleic acid is the second most abundant FA in milk fat and likely the main unsaturated FA involved in regulating fluidity of milk. Because the mammary gland can desaturate C18:0 to oleic acid, C18:0 appears to have a more prominent role in milk production than C16:0. To understand metabolism and utilization of these FA in lactating dairy cows, we reviewed production and milk fat synthesis studies. Additional and longer lactation studies on feeding both FA to lactating dairy cows are required to better delineate their roles in optimizing milk production and milk FA composition and yield.

  8. Effects of Heat Shock on Amino Acid Metabolism of Cowpea Cells 1

    PubMed Central

    Mayer, Randall R.; Cherry, Joe H.; Rhodes, David

    1990-01-01

    When cowpea (Vigna unguiculata) cells maintained at 26°C are transferred to 42°C, rapid accumulation of γ-aminobutyrate (>10-fold) is induced. Several other amino acids (including β-alanine, alanine, and proline) are also accumulated, but less extensively than γ-aminobutyrate. Total free amino acid levels are increased approximately 1.5-fold after 24 hours at 42°C. Heat shock also leads to release of amino acids into the medium, indicating heat shock damage to the integrity of the plasmalemma. Some of the changes in metabolic rates associated with heat shock were estimated by monitoring the 15N labeling kinetics of free intracellular, extracellular and protein-bound amino acids of cultures supplied with 15NH4+, and analyzing the labeling data by computer simulation. Preliminary computer simulation models of nitrogen flux suggest that heat shock induces an increase in the γ-aminobutyrate synthesis rate from 12.5 nanomoles per hour per gram fresh weight in control cells maintained at 26°C, to as high as 800 nanomoles per hour per gram fresh weight within the first 2 hours of heat shock. This 64-fold increase in the γ-aminobutyrate synthesis rate greatly exceeds the expected (Q10) change of metabolic rate of 2.5- to 3-fold due to a 16°C increase in temperature. We suggest that this metabolic response may in part involve an activation of glutamate decarboxylase in vivo, perhaps mediated by a transient cytoplasmic acidification. Proline appears to be synthesized from glutamate and not from ornithine in cowpea cells. Proline became severalfold more heavily labeled than ornithine, citrulline and arginine in both control and heat-shocked cultures. Proline synthesis rate was increased 2.7-fold by heat shock. Alanine, β-alanine, valine, leucine, and isoleucine synthesis rates were increased 1.6-, 3.5-, 2.0-, 5.0-, and 6.0-fold, respectively, by heat shock. In contrast, the phenylalanine synthesis rate was decreased by 50% in response to heat shock. The

  9. [Reponses of sugar metabolism in seed germination of three various acid-fast plants to acid rain].

    PubMed

    Wang, Li-Hong; Zhou, Qing; Zeng, Qing-Ling

    2008-03-01

    Responses of sugar metabolism during germination of rice (O. sativa ), wheat (T. aestivum) and rape (B. chinensis var. oleifera) seeds to simulated acid rain (pH 2.0, pH 2.5, pH 3.0, pH 3.5, pH 4.0, pH 4.5, pH 5.0) were investigated. The purpose was to clarify the mechanism of acid rain affecting seed germination. The results show that the alpha-amylase activity, contents of soluble sugar and reducing sugar of the rice, wheat and rape seeds decrease with increased stress level (pH 5.0 - 2.0), and are lower than CK. The response order of three indexes to stress level of acid rain is that rice (pH 3.5 - 4.0/53.88% - 77.7%) is smaller than wheat (pH 3.5 - 4.5/58.60% - 89.41%), and rape (pH 4.0 - 5.0/60.14% - 100%) is the smallest, alpha-amylase activity, contents of soluble sugar and reducing sugar of rice increase with prolonged stress time, but the three indexes of wheat and rape increase at first, and then decrease. In the same stress time (3 - 7 d), the three indexes of the three species for all treatment groups are lower than CK, and decrease with increased stress level. The stress time when the maximum damage of a-amylase activity, contents of soluble sugar and reducing sugar appeared is that rice (7 d, 7 d, 7 d) > wheat (7 d, 6 d, 5 d) > rape (3 d, 7 d, 5 d). Responses of three indexes to stress level and stress time of acid rain show that the ability of sugar metabolism resisting acid rain is that rice is stronger than wheat and rape is the worst, and the difference in sugar metabolism of 3 species is one of the internal reasons why the germination indexes behave differently.

  10. Soybean Seed Development: Fatty Acid and Phytohormone Metabolism and Their Interactions.

    PubMed

    Nguyen, Quoc Thien; Kisiala, Anna; Andreas, Peter; Neil Emery, R J; Narine, Suresh

    2016-06-01

    Vegetable oil utilization is determined by its fatty acid composition. In soybean and other grain crops, during the seed development oil accumulation is important trait for value in food or industrial applications. Seed development is relatively short and sensitive to unfavorable abiotic conditions. These stresses can lead to a numerous undesirable qualitative as well as quantitative changes in fatty acid production. Fatty acid manipulation which targets a higher content of a specific single fatty acid for food or industrial application has gained more attention. Despite several successes in modifying the ratio of endogenous fatty acids in most domesticated oilseed crops, numerous obstacles in FA manipulation of seed maturation are yet to be overcome. Remarkably, connections with plant hormones have not been well studied despite their critical roles in the regulation and promotion of a plethora of processes in plant growth and development. While activities of phytohormones during the reproductive phase have been partially clarified in seed physiology, the biological role of plant hormones in oil accumulation during seed development has not been investigated. In this review seed development and numerous effects of abiotic stresses are discussed. After describing fatty acid and phytohormone metabolism and their interactions, we postulate that the endogenous plant hormones play important roles in fatty acid production in soybean seeds.

  11. Hyaluronic acid as capacitation inductor: metabolic changes and membrane-associated adenylate cyclase regulation.

    PubMed

    Fernández, S; Córdoba, M

    2014-12-01

    The aim of this research was to study the effect of hyaluronic acid on bovine cryopreserved spermatozoa compared with heparin as regards the variation of capacitation induction, cellular oxidative metabolism and intracellular signal induced by membrane-associated adenylate cyclase to propose hyaluronic acid as a capacitation inductor. Heparin or hyaluronic acid and lysophosphatidylcholine were used to induce sperm capacitation and acrosome reaction, respectively. 2',5'-dideoxyadenosine was used as a membrane-associated adenylate cyclase inhibitor. The highest percentages of capacitated spermatozoa and live spermatozoa with acrosome integrity were obtained by incubating sperm for 60 min using 1000 μg/ml hyaluronic acid. In these conditions, capacitation induced by hyaluronic acid was lower compared with heparin; nonetheless both glycosaminoglycans promote intracellular changes that allow true acrosome reaction in vitro induced by lysophosphatidylcholine in bovine spermatozoa. Oxygen consumption in heparin-capacitated spermatozoa was significantly higher than in hyaluronic acid-treated spermatozoa. With all treatments, mitochondrial coupling was observed when a specific uncoupler of the respiratory chain was added. The inhibition of membrane-associated adenylate cyclase significantly blocked capacitation induction produced by hyaluronic acid, maintaining a basal sperm oxygen uptake in contrast to heparin effect in which both sperm parameters were inhibited, suggesting that the membrane-associated adenylate cyclase activation is involved in the intracellular signal mechanisms induced by both capacitation inductors, but only regulates mitochondrial oxidative phosphorylation in heparin-capacitated spermatozoa.

  12. The Relation between Photosynthesis, Respiration, and Crassulacean Acid Metabolism in Leaf Slices of Aloe arborescens Mill.

    PubMed

    Denius, H R; Homann, P H

    1972-06-01

    Leaves and leaf slices from Aloe arborescens Mill. were used to study the interrelations between Crassulacean acid metabolism, photosynthesis, and respiration. Oxygen exchange of leaf slices was measured polarographically. It was found that the photosynthetic utilization of stored malic acid resulted in a net evolution of oxygen. This oxygen production, and the decrease in acid content of the leaf tissue, were completely inhibited by amytal, although the rate of respiratory oxygen uptake was hardly affected by the presence of this inhibitor of mitochondrial electron transport. Other poisons of respiration (cyanide) and of the tricarboxylic acid cycle (trifluoroacetate, 2-diethyl malonate) also were effective in preventing acid-dependent oxygen evolution. It is concluded that the mobilization of stored acids during light-dependent deacidification of the leaves depends on the operation of the tricarboxylic acid cycle and of the electron transport of the mitochondria.A comparison of enzyme activities in extracts from Aloe leaves and from other plants and studies of leaf anatomy and chloroplast morphology revealed typical characteristics of C(3)-, as well as C(4)-, plants in Aloe.

  13. Soybean Seed Development: Fatty Acid and Phytohormone Metabolism and Their Interactions

    PubMed Central

    Nguyen, Quoc Thien.; Kisiala, Anna; Andreas, Peter; Neil Emery, R.J.; Narine, Suresh

    2016-01-01

    Vegetable oil utilization is determined by its fatty acid composition. In soybean and other grain crops, during the seed development oil accumulation is important trait for value in food or industrial applications. Seed development is relatively short and sensitive to unfavorable abiotic conditions. These stresses can lead to a numerous undesirable qualitative as well as quantitative changes in fatty acid production. Fatty acid manipulation which targets a higher content of a specific single fatty acid for food or industrial application has gained more attention. Despite several successes in modifying the ratio of endogenous fatty acids in most domesticated oilseed crops, numerous obstacles in FA manipulation of seed maturation are yet to be overcome. Remarkably, connections with plant hormones have not been well studied despite their critical roles in the regulation and promotion of a plethora of processes in plant growth and development. While activities of phytohormones during the reproductive phase have been partially clarified in seed physiology, the biological role of plant hormones in oil accumulation during seed development has not been investigated. In this review seed development and numerous effects of abiotic stresses are discussed. After describing fatty acid and phytohormone metabolism and their interactions, we postulate that the endogenous plant hormones play important roles in fatty acid production in soybean seeds. PMID:27252591

  14. Histochemical Compartmentation of Photosynthesis in the Crassulacean Acid Metabolism Plant Crassula falcata1

    PubMed Central

    Springer, Stefan A.; Outlaw, William H.

    1988-01-01

    The succulent leaf of the obligate Crassulacean acid metabolism plant Crassula falcata comprises two distinct types of parenchyma. The peripheral tissue is dark green, whereas the central tissue is relatively colorless. We have investigated whether the conventional interpretation of Crassulacean acid metabolism—simply, temporal separation of light and dark CO2 fixation within individual cells—is sufficient. Ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) and chlorophyll, indicating the photosynthetic-carbon-reduction pathway, were concentrated in peripheral tissue. Specific activities of P-enolpyruvate carboxylase (4.1.1.31) and of NAD+-malic enzyme (1.1.1.39), indicating capacity for dark CO2 fixation and release, respectively, were high in both types of parenchyma. Measured directly as malic acid decline at the beginning of the photoperiod, CO2 “storage” occurred in both tissues. These data indicate that there is a spatial component to Crassulacean acid metabolism in C. falcata. Images Fig. 1 Fig. 2 Fig. 5 PMID:16666360

  15. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation.

    PubMed

    Oexle, H; Gnaiger, E; Weiss, G

    1999-11-10

    Iron modulates the expression of the critical citric acid cycle enzyme aconitase via a translational mechanism involving iron regulatory proteins. Thus, the present study was undertaken to investigate the consequences of iron perturbation on citric acid cycle activity, oxidative phosphorylation and mitochondrial respiration in the human cell line K-562. In agreement with previous data iron increases the activity of mitochondrial aconitase while it is reduced upon addition of the iron chelator desferrioxamine (DFO). Interestingly, iron also positively affects three other citric acid cycle enzymes, namely citrate synthase, isocitric dehydrogenase, and succinate dehydrogenase, while DFO decreases the activity of these enzymes. Consequently, iron supplementation results in increased formation of reducing equivalents (NADH) by the citric acid cycle, and thus in increased mitochondrial oxygen consumption and ATP formation via oxidative phosphorylation as shown herein. This in turn leads to downregulation of glucose utilization. In contrast, all these metabolic pathways are reduced upon iron depletion, and thus glycolysis and lactate formation are significantly increased in order to compensate for the decrease in ATP production via oxidative phosphorylation in the presence of DFO. Our results point to a complex interaction between iron homeostasis, oxygen supply and cellular energy metabolism in human cells.

  16. Relationships between Stomatal Behavior and Internal Carbon Dioxide Concentration in Crassulacean Acid Metabolism Plants

    PubMed Central

    Cockburn, William; Ting, Irwin P.; Sternberg, Leonel O.

    1979-01-01

    Measurements of internal gas phase CO2 concentration, stomatal resistance, and acid content were made in Crassulacean acid metabolism plants growing under natural conditions. High CO2 concentrations, sometimes in excess of 2%, were observed during the day in a range of taxonomically widely separated plants (Opuntia ficus-indica L., Opuntia basilaris Engelm. and Bigel., Agave desertii Engelm., Yucca schidigera Roezl. ex Ortiges, Ananas comosus [L.] Merr., Aloe vera L., Cattleya sp. and Phalanopsis sp.) and below ambient air concentrations were observed at night. Stomatal resistance was always high when CO2 concentration was high and experiments in which attempts were made to manipulate internal CO2 concentrations gave data consistent with stomatal behavior in Crassulacean acid metabolism being controlled by internal CO2 concentration. Exogenous CO2 applied in darkness at a concentration similar to those observed in the light caused stomatal resistance to increase. In pads of Opuntia basilaris Engelm. and Bigel. subjected to severe water stress internal gas phase CO2 concentrations exhibited fluctuations opposite in phase to fluctuations in acid content. Stomatal resistance remained high and the opening response to low CO2 concentration was almost entirely eliminated. PMID:16660851

  17. Relationships between Stomatal Behavior and Internal Carbon Dioxide Concentration in Crassulacean Acid Metabolism Plants.

    PubMed

    Cockburn, W

    1979-06-01

    Measurements of internal gas phase CO(2) concentration, stomatal resistance, and acid content were made in Crassulacean acid metabolism plants growing under natural conditions. High CO(2) concentrations, sometimes in excess of 2%, were observed during the day in a range of taxonomically widely separated plants (Opuntia ficus-indica L., Opuntia basilaris Engelm. and Bigel., Agave desertii Engelm., Yucca schidigera Roezl. ex Ortiges, Ananas comosus [L.] Merr., Aloe vera L., Cattleya sp. and Phalanopsis sp.) and below ambient air concentrations were observed at night.Stomatal resistance was always high when CO(2) concentration was high and experiments in which attempts were made to manipulate internal CO(2) concentrations gave data consistent with stomatal behavior in Crassulacean acid metabolism being controlled by internal CO(2) concentration. Exogenous CO(2) applied in darkness at a concentration similar to those observed in the light caused stomatal resistance to increase.In pads of Opuntia basilaris Engelm. and Bigel. subjected to severe water stress internal gas phase CO(2) concentrations exhibited fluctuations opposite in phase to fluctuations in acid content. Stomatal resistance remained high and the opening response to low CO(2) concentration was almost entirely eliminated.

  18. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    PubMed Central

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  19. Amino Acid Mixture Enriched With Arginine, Alanine, and Phenylalanine Stimulates Fat Metabolism During Exercise.

    PubMed

    Ueda, Keisuke; Nakamura, Yutaka; Yamaguchi, Makoto; Mori, Takeshi; Uchida, Masayuki; Fujita, Satoshi

    2016-02-01

    Although there have been many investigations of the beneficial effects of both exercise and amino acids (AAs), little is known about their combined effects on the single-dose ingestion of AAs for lipid metabolism during exercise. We hypothesize that taking a specific combination of AAs implicated in glucagon secretion during exercise may increase fat metabolism. We recently developed a new mixture, d-AA mixture (D-mix), that contains arginine, alanine, and phenylalanine to investigate fat oxidation. In a double-blind, placebo-controlled crossover study, 10 healthy male volunteers were randomized to ingest either D-mix (3 g/dose) or placebo. Subjects in each condition subsequently performed a physical task that included workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 hr. After oral intake of D-mix, maximum serum concentrations of glycerol (9.32 ± 6.29 mg/L and 5.22 ± 2.22 mg/L, respectively; p = .028), free fatty acid level (0.77 ± 0.26 mEq/L and 0.63 ± 0.28 mEq/L, respectively; p = .022), and acetoacetic acid levels (37.9 ± 17.7 μmol/L and 30.3 ± 13.9 μmol/L, respectively; p = .040) were significantly higher than in the placebo groups. The area under the curve for glucagon during recovery was numerically higher than placebo (6.61 ± 1.33 μg/L · min and 6.06 ± 1.23 μg/L · min, respectively; p = .099). These results suggest that preexercise ingestion of D-mix may stimulate fat metabolism. Combined with exercise, the administration of AA mixtures could prove to be a useful nutritional strategy to maximize fat metabolism.

  20. Stimulus-specific induction of phospholipid and arachidonic acid metabolism in human neutrophils

    SciTech Connect

    Godfrey, R.W.; Manzi, R.M.; Clark, M.A.; Hoffstein, S.T.

    1987-04-01

    Phospholipid remodeling resulting in arachidonic acid (AA) release and metabolism in human neutrophils stimulated by calcium ionophore A23187 has been extensively studied, while data obtained using physiologically relevant stimuli is limited. Opsonized zymosan and immune complexes induced stimulus-specific alterations in lipid metabolism that were different from those induced by A23187. (/sup 3/H)AA release correlated with activation of phospholipase A2 (PLA2) but not with cellular activation as indicated by superoxide generation. The latter correlated more with calcium-dependent phospholipase C (PLC) activation and elevation of cellular diacylglycerol (DAG) levels. When cells that had been allowed to incorporate (/sup 3/H)AA were stimulated with A23187, large amounts of labeled AA was released, most of which was metabolized to 5-HETE and leukotriene B4. Stimulation with immune complexes also resulted in the release of (/sup 3/H)AA but this released radiolabeled AA was not metabolized. In contrast, stimulation with opsonized zymosan induced no detectable release of (/sup 3/H)AA. Analysis of (/sup 3/H)AA-labeled lipids in resting cells indicated that the greatest amount of label was incorporated into the phosphatidylinositol (PI) pool, followed closely by phosphatidylcholine and phosphatidylserine, while little (/sup 3/H)AA was detected in the phosphatidylethanolamine pool. During stimulation with A23187, a significant decrease in labeled PI occurred and labeled free fatty acid in the pellet increased. With immune complexes, only a small decrease was seen in labeled PI while the free fatty acid in the pellets was unchanged. In contrast, opsonized zymosan decreased labeled PI, and increased labeled DAG. Phospholipase activity in homogenates from human neutrophils was also assayed. A23187 and immune complexes, but not zymosan, significantly enhanced PLA2 activity in the cell homogenates. On the other hand, PLC activity was enhanced by zymosan and immune complexes

  1. On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism.

    PubMed

    Ikon, Nikita; Ryan, Robert O

    2016-09-01

    3-methylglutaconic acid (3MGA)-uria occurs in numerous inborn errors of metabolism (IEM) associated with compromised mitochondrial energy metabolism. This organic acid arises from thioester cleavage of 3-methylglutaconyl CoA (3MG CoA), an intermediate in leucine catabolism. In individuals harboring mutations in 3MG CoA hydratase (i.e., primary 3MGA-uria), dietary leucine is the source of 3MGA. In secondary 3MGA-uria, however, no leucine metabolism defects have been reported. While others have suggested 3MGA arises from aberrant isoprenoid shunting from cytosol to mitochondria, an alternative route posits that 3MG CoA arises in three steps from mitochondrial acetyl CoA. Support for this biosynthetic route in IEMs is seen by its regulated occurrence in microorganisms. The fungus, Ustilago maydis, the myxobacterium, Myxococcus xanthus and the marine cyanobacterium, Lyngbya majuscule, generate 3MG CoA (or acyl carrier protein derivative) in the biosynthesis of iron chelating siderophores, iso-odd chain fatty acids and polyketide/nonribosomal peptide products, respectively. The existence of this biosynthetic machinery in these organisms supports a model wherein, under conditions of mitochondrial dysfunction, accumulation of acetyl CoA in the inner mitochondrial space as a result of inefficient fuel utilization drives de novo synthesis of 3MG CoA. Since humans lack the downstream biosynthetic capability of the organisms mentioned above, as 3MG CoA levels rise, thioester hydrolysis yields 3MGA, which is excreted in urine as unspent fuel. Understanding the metabolic origins of 3MGA may increase its utility as a biomarker.

  2. CHARACTERIZATION OF CYPS IN THE METABOLISM OF ALL TRANS RETINOIC ACID BY LIVER MICROSOMES FROM MICE TREATED WITH CONAZOLES

    EPA Science Inventory

    Conazoles are fungicides used in crop protection and as pharmaceuticals. Triadimefon and propiconazole are hepatotumorigenic in mice, while myclobutanil is not. Previous toxicogenomic studies suggest that alteration of the retinoic acid metabolism pathway may involve in conazole-...

  3. Dietary Omega-3 Fatty Acid Deficiency and High Fructose intake in the Development of Metabolic Syndrome Brain, Metabolic Abnormalities, and Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Simopoulos, Artemis P.

    2013-01-01

    Western diets are characterized by both dietary omega-3 fatty acid deficiency and increased fructose intake. The latter found in high amounts in added sugars such as sucrose and high fructose corn syrup (HFCS). Both a low intake of omega-3 fatty acids or a high fructose intake contribute to metabolic syndrome, liver steatosis or non-alcoholic fatty liver disease (NAFLD), promote brain insulin resistance, and increase the vulnerability to cognitive dysfunction. Insulin resistance is the core perturbation of metabolic syndrome. Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function. Fish oil supplementation maintains proper insulin signaling in the brain, ameliorates NAFLD and decreases the risk to metabolic syndrome suggesting that adequate levels of omega-3 fatty acids in the diet can cope with the metabolic challenges imposed by high fructose intake in Western diets which is of major public health importance. This review presents the current status of the mechanisms involved in the development of the metabolic syndrome, brain insulin resistance, and NAFLD a most promising area of research in Nutrition for the prevention of these conditions, chronic diseases, and improvement of Public Health. PMID:23896654

  4. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    PubMed

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease.

  5. Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes.

    PubMed

    Mamoon, Abulkhair; Subauste, Angela; Subauste, Maria C; Subauste, Jose

    2014-10-25

    Retinoic acid (RA) affects multiple aspects of development, embryogenesis and cell differentiation processes. The liver is a major organ that stores RA suggesting that retinoids play an important role in the function of hepatocytes. In our previous studies, we have demonstrated the involvement of small heterodimer partner (SHP) in RA-induced signaling in a non-transformed hepatic cell line AML 12. In the present study, we have identified several critical genes in lipid homeostasis (Apoa1, Apoa2 and ApoF) that are repressed by RA-treatment in a SHP dependent manner, in vitro and also in vivo with the use of the SHP null mice. In a similar manner, RA also represses several critical genes involved in bile acid metabolism (Cyp7a1, Cyp8b1, Mdr2, Bsep, Baat and Ntcp) via upregulation of SHP. Collectively our data suggest that SHP plays a major role in RA-induced potential changes in pathophysiology of metabolic disorders in the liver.

  6. Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

  7. Comparison of amino acid profiles and metabolic gene expression in muskrat scented glands in secretion and non-secretion season

    PubMed Central

    Li, Yimeng; Zhang, Tianxiang; Fan, Mengyuan; Zhou, Juntong; Yang, Shuang; Zhang, Meishan; Qi, Lei; Lin, Shaobi; Hu, Defu; Liu, Shuqiang

    2017-01-01

    The scented gland is an organ responsible for producing musk in muskrats. During musk secretion season, the metabolism of glandular cells increases in the scented glands and a large amount of musk is synthesised. In this study, we collected scented gland arterial blood from six healthy adult male muskrats during non-secretion season (November). We also obtained scented gland arterial blood, venous blood, and musk from six healthy adult males during secretion season (March). Qualitative and quantitative analyses of free amino acids in blood and musk were performed with an automated amino acid analyzer. Additionally, we employed RNA sequencing technology to study the expression patterns of amino acid metabolic pathways in scented glands. Amino acid profile analysis indicates that scented glands can concentrate amino acids during secretion season, and transcriptome analysis suggests that some amino acid metabolism-related genes undergo significant seasonal changes. In summary, scented gland amino acid metabolism displays seasonal differences. Elevated amino acid metabolic activity during secretion season sustains the glands’ secretory function. PMID:28145478

  8. Comparison of amino acid profiles and metabolic gene expression in muskrat scented glands in secretion and non-secretion season.

    PubMed

    Li, Yimeng; Zhang, Tianxiang; Fan, Mengyuan; Zhou, Juntong; Yang, Shuang; Zhang, Meishan; Qi, Lei; Lin, Shaobi; Hu, Defu; Liu, Shuqiang

    2017-02-01

    The scented gland is an organ responsible for producing musk in muskrats. During musk secretion season, the metabolism of glandular cells increases in the scented glands and a large amount of musk is synthesised. In this study, we collected scented gland arterial blood from six healthy adult male muskrats during non-secretion season (November). We also obtained scented gland arterial blood, venous blood, and musk from six healthy adult males during secretion season (March). Qualitative and quantitative analyses of free amino acids in blood and musk were performed with an automated amino acid analyzer. Additionally, we employed RNA sequencing technology to study the expression patterns of amino acid metabolic pathways in scented glands. Amino acid profile analysis indicates that scented glands can concentrate amino acids during secretion season, and transcriptome analysis suggests that some amino acid metabolism-related genes undergo significant seasonal changes. In summary, scented gland amino acid metabolism displays seasonal differences. Elevated amino acid metabolic activity during secretion season sustains the glands' secretory function.

  9. Study of metabolic profile of Rhizopus oryzae to enhance fumaric acid production under low pH condition.

    PubMed

    Liu, Ying; Xu, Qing; Lv, Chunwei; Yan, Caixia; Li, Shuang; Jiang, Ling; Huang, He; Ouyang, Pingkai

    2015-12-01

    Ensuring a suitable pH is a major problem in industrial organic acid fermentation. To circumvent this problem, we used a metabolic profiling approach to analyze metabolite changes in Rhizopus oryzae under different pH conditions. A correlation between fumaric acid production and intracellular metabolic characteristics of R. oryzae was revealed by principal component analysis. The results showed that to help cell survival in the presence of low pH, R. oryzae altered amino acid and fatty acid metabolism and promoted sugar or sugar alcohol synthesis, corresponding with a suppressing of energy metabolism, phenylalanine, and tyrosine synthesis and finally resulting in the low performance of fumaric acid production. Based on this observation, 1 % linoleic acid was added to the culture medium in pH 3.0 to decrease the carbon demand for cell survival, and the fumaric acid titer was enhanced by 39.7 % compared with the control (pH 3.0 without linoleic acid addition), reaching 18.3 g/L after 84 h of fermentation. These findings provide new insights into the mechanism by which R. oryzae responds to acidic stress and would be helpful for the development of efficient strategies for fumaric acid production at low pH.

  10. Postoperative metabolic alkalosis and acute renal failure: rationale for the use of hydrochloric acid.

    PubMed

    Shavelle, H S; Parke, R

    1975-10-01

    Metabolic alkalosis secondary to chloride depletion, especially following gastrointestinal surgery and associated with acute renal failure, is a frequent clinical occurrence. Management of the resultant acid-base disturbance mandates chloride replacement. The presence of oliguria limits the choice of accompanying cation. The use of intravenous hydrochloric acid to correct and maintain proper chloride balance, secondary to external gastric fluid losses, is recommended as a straightforward approach. Two brief case synopses are presented. Both patients, florid examples of profound chloride depletion, required large amounts of intravenous hydrochloric acid. The options regarding the choice of chloride solution, hazards involved, and a simplified schema of replacement therapy are presented. Combined gastrointestinal and renal dysfunction create unusual biochemical and clinical alterations and may result in a complex management problem.