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Sample records for 6-18ffluoro-l-dopa fdopa metabolism

  1. Sensitivity of kinetic macro parameters to changes in dopamine synthesis, storage, and metabolism: a simulation study for [¹⁸F]FDOPA PET by a model with detailed dopamine pathway.

    PubMed

    Matsubara, Keisuke; Watabe, Hiroshi; Kumakura, Yoshitaka; Hayashi, Takuya; Endres, Christopher J; Minato, Kotaro; Iida, Hidehiro

    2011-08-01

    Quantitative interpretation of brain [¹⁸F]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [¹⁸F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage, and catabolism from (18) F-labeled dopamine to DOPAC and HVA. A macro parameter most sensitive to the changes of these processes would be potentially beneficial to identify impaired processes in a neurodegenerative disorder such as Parkinson's disease. The purpose of this study is a systematic comparison of several [¹⁸F]FDOPA macro parameters in terms of sensitivities to process-specific changes in simulated time-activity curve (TAC) data of [¹⁸F]FDOPA PET. We introduced a multiple-compartment kinetic model to simulate PET TACs with physiological changes in the dopamine pathway. TACs in the alteration of dopamine synthesis, storage, and metabolism were simulated with a plasma input function obtained by a non-human primate [¹⁸F]FDOPA PET study. Kinetic macro parameters were calculated using three conventional linear approaches (Gjedde-Patlak, Logan, and Kumakura methods). For simulated changes in dopamine storage and metabolism, the slow clearance rate (k(loss) ) as calculated by the Kumakura method showed the highest sensitivity to these changes. Although k(loss) performed well at typical ROI noise levels, there was large bias at high noise level. In contrast, for simulated changes in DDC activity it was found that K(i) and V(T), estimated by Gjedde-Patlak and Logan method respectively, have better performance than k(loss). PMID:21190220

  2. Lateralisation of striatal function: evidence from 18F-dopa PET in Parkinson's disease

    PubMed Central

    Cheesman, A; Barker, R; Lewis, S; Robbins, T; Owen, A; Brooks, D

    2005-01-01

    Objectives: The aetiology of the cognitive changes seen in Parkinson's disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using 18F-6-fluorodopa positron emission tomography (18F-dopa PET) in PD subjects with early cognitive changes. Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and 18F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which 18F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET. Results: SPM localised significant covariation between right caudate 18F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and 18F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes. PMID:16107352

  3. Comparative study of 18F-DOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors

    PubMed Central

    Jacob, Mattakarottu J; Pandit, Aniruddha G; Jora, Charu; Mudalsha, Ravina; Sharma, Amit; Pathak, Harish C

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT in primary brain tumors. We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 18F-FDOPA, 13N-Ammonia and F18-FDG PET/CT. Materials and Methods: Nine patients undergoing evaluation for brain tumors were studied. Tracer uptake was quantified by the use of standardized uptake values and the ratio of tumor uptake to normal identical area of contra lateral hemisphere (T/N). In addition, PET uptake with 18F-FDOPA was quantified by use of ratio of tumor uptake to striatum uptake (T/S). The results were correlated with the patient's clinical profile. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA. The sensitivity for identifying tumors was substantially higher with 18F-FDOPA PET than with F18-FDG and 13N-Ammonia PET as determined by simple visual inspection. The sensitivity for identifying recurrence in low grade gliomas is higher with 13N-Ammonia than with F18-FDG. Conclusion: 18F-FDOPA PET is more reliable than F18-FDG and 13N-Ammonia PET for evaluating brain tumors. PMID:23326065

  4. Dual acquisition of 18F-FMISO and 18F-FDOPA

    NASA Astrophysics Data System (ADS)

    Bell, Christopher; Rose, Stephen; Puttick, Simon; Pagnozzi, Alex; Poole, Christopher M.; Gal, Yaniv; Thomas, Paul; Fay, Michael; Jeffree, Rosalind L.; Dowson, Nicholas

    2014-07-01

    Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

  5. Striatal FDOPA uptake and cognition in advanced non-demented Parkinson's disease: a clinical and FDOPA-PET study.

    PubMed

    van Beilen, Marije; Portman, Axel T; Kiers, Henk A L; Maguire, Ralph P; Kaasinen, Valtteri; Koning, Marthe; Pruim, Jan; Leenders, Klaus L

    2008-01-01

    This study sought to determine the nature of the relationship between cognition and striatal dopaminergic functioning in 28 patients with advanced Parkinson's disease (PD) using fluorodopa Positron emission tomography (FDOPA-PET) and neuropsychological test scores. Mental flexibility was related to putamen activity while mental organization (executive memory and fluency) was related to caudate FDOPA uptake. Interestingly, the caudate may be more important in the mental components of executive functioning, while the putamen may be more important in the motor components of executive functioning. PMID:18249027

  6. Contribution of FDOPA PET to radiotherapy planning for advanced glioma

    NASA Astrophysics Data System (ADS)

    Dowson, Nicholas; Fay, Michael; Thomas, Paul; Jeffree, Rosalind; McDowall, Robert; Winter, Craig; Coulthard, Alan; Smith, Jye; Gal, Yaniv; Bourgeat, Pierrick; Salvado, Olivier; Crozier, Stuart; Rose, Stephen

    2014-03-01

    Despite radical treatment with surgery, radiotherapy and chemotherapy, advanced gliomas recur within months. Geographic misses in radiotherapy planning may play a role in this seemingly ineluctable recurrence. Planning is typically performed on post-contrast MRIs, which are known to underreport tumour volume relative to FDOPA PET scans. FDOPA PET fused with contrast enhanced MRI has demonstrated greater sensitivity and specificity than MRI alone. One sign of potential misses would be differences between gross target volumes (GTVs) defined using MRI alone and when fused with PET. This work examined whether such a discrepancy may occur. Materials and Methods: For six patients, a 75 minute PET scan using 3,4-dihydroxy-6-18F-fluoro-L-phynel-alanine (18F-FDOPA) was taken within 2 days of gadolinium enhanced MRI scans. In addition to standard radiotherapy planning by an experienced radiotherapy oncologist, a second gross target volume (GTV) was defined by an experienced nuclear medicine specialist for fused PET and MRI, while blinded to the radiotherapy plans. The volumes from standard radiotherapy planning were compared to the PET defined GTV. Results: The comparison indicated radiotherapy planning would change in several cases if FDOPA PET data was available. PET-defined contours were external to 95% prescribed dose for several patients. However, due to the radiotherapy margins, the discrepancies were relatively small in size and all received a dose of 50 Gray or more. Conclusions: Given the limited size of the discrepancies it is uncertain that geographic misses played a major role in patient outcome. Even so, the existence of discrepancies indicates that FDOPA PET could assist in better defining margins when planning radiotherapy for advanced glioma, which could be important for highly conformal radiotherapy plans.

  7. The sensitivity and specificity of F-DOPA PET in a movement disorder clinic

    PubMed Central

    Ibrahim, Nevein; Kusmirek, Joanna; Struck, Aaron F; Floberg, John M; Perlman, Scott B; Gallagher, Catherine; Hall, Lance T

    2016-01-01

    Idiopathic Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with nigral degeneration or striatal dopamine deficiency. Therefore, the early clinical diagnosis alone may not be accurate and this reinforces the importance of functional imaging targeting the pathophysiology of the disease process. 18F-DOPA L-6-[18F] fluoro-3,4-dihydroxyphenylalnine (18F-DOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the monoaminergic disturbances in PD. In this study, we aim to illustrate our local experience to determine the accuracy of 18F-DOPA PET for diagnosis of PD. We studied a total of 27 patients. A retrospective analysis was carried out for all patients that underwent 18F-DOPA PET brain scan for motor symptoms suspicious for PD between 2001-2008. Both qualitative and semi-quantitative analyses of the scans were performed. The patient’s medical records were then assessed for length of follow-up, response to levodopa, clinical course of illness, and laterality of symptoms at time of 18F-DOPA PET. The eventual diagnosis by the referring neurologist, movement disorder specialist, was used as the reference standard for further analysis. Of the 28 scans, we found that one was a false negative, 20 were true positives, and 7 were true negatives. The resultant values are Sensitivity 95.4% (95% CI: 100%-75.3%), Specificity 100% (95% CI: 100%-59.0%), PPV 100% (95% CI 100%-80.7%), and NPV 87.5% (95% CI: 99.5%-50.5%). PMID:27069770

  8. Diagnostic FDG and FDOPA positron emission tomography scans distinguish the genomic type and treatment outcome of neuroblastoma

    PubMed Central

    Chang, Hsiu-Hao; Lu, Ching-Chu; Lin, Dong-Tsamn; Jou, Shiann-Tarng; Yang, Yung-Li; Lee, Ya-Ling; Huang, Shiu-Feng; Jeng, Yung-Ming; Lee, Hsinyu; Miser, James S.; Lin, Kai-Hsin; Liao, Yung-Feng; Hsu, Wen-Ming; Tzen, Kai-Yuan

    2016-01-01

    Neuroblastoma (NB) is a heterogeneous childhood cancer that requires multiple imaging modalities for accurate staging and surveillances. This study aims to investigate the utility of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-dihydroxyphenylalanine (FDOPA) in determining the prognosis of NB. During 2007–2014, forty-two NB patients (male:female, 28:14; median age, 2.0 years) undergoing paired FDG and FDOPA PET scans at diagnosis were evaluated for the maximum standardized uptake value (SUVmax) of FDG or FDOPA by the primary tumor. Patients with older age, advanced stages, or MYCN amplification showed higher FDG and lower FDOPA SUVmax (all P < 0.02). Receiver operating characteristics analysis identified FDG SUVmax≥ 3.31 and FDOPA SUVmax < 4.12 as an ultra-high-risk feature (PET-UHR) that distinguished the most unfavorable genomic types, i.e. segmental chromosomal alterations and/or MYCN amplification, at a sensitivity of 81.3% (54.4%–96.0%) and a specificity of 93.3% (68.1%–99.8%). Considering with age, stage, MYCN status, and anatomical image-defined risk factor, PET-UHR was an independent predictor of inferior event-free survival (multivariate hazard ratio, 4.9 [1.9–30.1]; P = 0.012). Meanwhile, the ratio between FDG and FDOPA SUVmax (G:D) correlated positively with HK2 (Spearman's ρ = 0.86, P < 0.0001) and negatively with DDC (ρ = −0.58, P = 0.02) gene expression levels, which might suggest higher glycolytic activity and less catecholaminergic differentiation in NB tumors taking up higher FDG and lower FDOPA. In conclusion, the intensity of FDG and FDOPA uptake on diagnostic PET scans may predict the tumor behavior and complement the current risk stratification systems of NB. PMID:26959748

  9. Relation of 18-F-Dopa PET with hypokinesia-rigidity, tremor and freezing in Parkinson’s disease

    PubMed Central

    Pikstra, Angelina R.A.; van der Hoorn, Anouk; Leenders, Klaus L.; de Jong, Bauke M.

    2016-01-01

    Introduction In this retrospective study concerning patients with Parkinson's disease (PD) scanned with 18-F-Dopa PET (N = 129), we looked for an association between reduced 18-F-Dopa uptake and the key PD symptoms tremor and hypokinesia-rigidity. We hypothesized to find a stronger correlation between dopaminergic depletion in the striatum and hypokinesia-rigidity compared to tremor. Methods The onset side of symptoms (documented for 102 patients) as well as the first registered UPDRS (available for 79 patients) was used to correlate with F-Dopa uptake values in the caudate nucleus and putamen in this large retrospective sample. Results Reduced F-Dopa uptake was contralateral to hypokinesia-rigidity symptoms and correlated with its severity (quantified by UPDRS). For tremor severity, no correlation was seen with F-Dopa reduction. Furthermore, freezing of gait correlated with reduced F-Dopa uptake in the putamen of the right hemisphere. Conclusion and discussion Our results, obtained in a large patient group, provides support for the concept that tremor in PD is not only based on a dopamine related pathway but may rely on a different pathway. PMID:26909330

  10. [18F]FDOPA PET as an endophenotype for Parkinson's Disease linkage studies.

    PubMed

    Racette, Brad A; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M; Videen, Tom O; Perlmutter, Joel S

    2006-04-01

    Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

  11. [18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

    PubMed Central

    Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

    2008-01-01

    Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

  12. Reduced uptake of [18F]FDOPA PET in asymptomatic welders with occupational manganese exposure

    PubMed Central

    Criswell, S.R.; Perlmutter, J.S.; Videen, T.O.; Moerlein, S.M.; Flores, H.P.; Birke, A.M.

    2011-01-01

    Background: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[18F]fluoro-l-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine whether welding exposure is associated with damage to nigrostriatal neurons in asymptomatic workers. Methods: We imaged 20 asymptomatic welders exposed to Mn fumes, 20 subjects with idiopathic Parkinson disease (IPD), and 20 normal controls using FDOPA PET. All subjects were examined by a movement disorders specialist. Basal ganglia volumes of interest were identified for each subject. The specific uptake of FDOPA, Ki, was generated for each region using graphical analysis method. Results: Repeated measures general linear model (GLM) analysis demonstrated a strong interaction between diagnostic group and region (F4,112 = 15.36, p < 0.001). Caudate Kis were lower in asymptomatic welders (0.0098 + 0.0013 minutes−1) compared to control subjects (0.0111 + 0.0012 minutes−1, p = 0.002). The regional pattern of uptake in welders was most affected in the caudate > anterior putamen > posterior putamen. This uptake pattern was anatomically reversed from the pattern found in subjects with IPD. Conclusions: Active, asymptomatic welders with Mn exposure demonstrate reduced FDOPA PET uptake indicating dysfunction in the nigrostriatal dopamine system. The caudate Ki reduction in welders may represent an early (asymptomatic) marker of Mn neurotoxicity and appears to be distinct from the pattern of dysfunction found in symptomatic IPD. PMID:21471467

  13. 18F-DOPA PET/CT in Orbital Metastasis From Medullary Thyroid Carcinoma.

    PubMed

    Ruiz, Jean-Baptiste; Orré, Mathieu; Cazeau, Anne-Laure; Henriques de Figueiredo, Bénédicte; Godbert, Yann

    2016-06-01

    A 53-year-old-woman is being followed up for a sporadic medullary thyroid carcinoma that was initially treated surgically. Nine years later, a progressive increase in calcitonin levels along with headaches was observed. An orbital metastasis from medullary thyroid carcinoma was diagnosed by performing an F-DOPA PET/CT. The orbital lesion was treated by an external beam radiation. Four months later, an MRI revealed a global morphological stability and a reduction in calcitonin levels. PMID:27055131

  14. 18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

    PubMed

    Calabria, Ferdinando F; Chiaravalloti, Agostino; Calabria, Eros N; Grillea, Giovanni; Schillaci, Orazio

    2016-08-01

    A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas. PMID:27187729

  15. Differing patterns of striatal sup 18 F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

    SciTech Connect

    Brooks, D.J.; Ibanez, V.; Sawle, G.V.; Quinn, N.; Lees, A.J.; Mathias, C.J.; Bannister, R.; Marsden, C.D.; Frackowiak, R.S. )

    1990-10-01

    Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.

  16. Orbitofrontal (18) F-DOPA Uptake and Movement Preparation in Parkinson's Disease.

    PubMed

    Marinelli, Lucio; Piccardo, Arnoldo; Mori, Laura; Morbelli, Silvia; Girtler, Nicola; Castaldi, Antonio; Picco, Agnese; Trompetto, Carlo; Ghilardi, Maria Felice; Abbruzzese, Giovanni; Nobili, Flavio

    2015-01-01

    In Parkinson's disease (PD) degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD. The aim of this study is to characterize the role of dopamine on the cognitive processes that precede movement in a reaction time paradigm in PD. We enrolled 16 newly diagnosed and untreated patients with PD without cognitive impairment or depression and 10 control subjects with essential tremor. They performed multiple-choice reaction time task with the right upper limb and brain (18)F-DOPA PET/CT scan. A significant inverse correlation was highlighted between average reaction time and (18)F-DOPA uptake in the left lateral orbitofrontal cortex. No correlations were found between reaction time and PD disease severity or between reaction time and (18)F-DOPA uptake in controls. Our study shows that in PD, but not in controls, reaction time is inversely related to the levels of dopamine in the left lateral orbitofrontal cortex. This novel finding underlines the role of dopamine in the lateral orbitofrontal cortex in the early stages of PD, supporting a relation between the compensatory cortical dopamine and movement preparation. PMID:26171275

  17. Postinjection L-phenylalanine increases basal ganglia contrast in PET scans of 6-18F-DOPA

    SciTech Connect

    Doudet, D.J.; McLellan, C.A.; Aigner, T.G.; Wyatt, R.; Adams, H.R.; Miyake, H.; Finn, R.T.; Cohen, R.M. )

    1991-07-01

    The sensitivity of 18F-DOPA positron emission tomography for imaging presynaptic dopamine systems is limited by the amount of specific-to-nonspecific accumulation of radioactivity in brain. In rhesus monkeys, we have been able to increase this ratio by taking advantage of the lag time between 18F-DOPA injection and the formation of its main metabolite, the amino acid 18F-fluoromethoxydopa, the entrance of which into brain is responsible for most of the brain's nonspecific radioactivity. By infusing an unlabeled amino acid, L-phenylalanine, starting 15 min after 18F-DOPA administration, we preferentially blocked the accumulation of 18F-fluoromethoxydopa by preventing its entrance into brain through competition at the large neutral amino acid transport system of the blood-brain barrier. This method appears as reliable as the original and more sensitive, as demonstrated by the comparison of normal and MPTP-treated animals under both conditions.

  18. Adrenal Metastasis of a Poorly Differentiated Adenocarcinoma Mimicking a Pheochromocytoma on 18F-FDOPA PET/CT.

    PubMed

    Heimburger, Céline; Averous, Gerlinde; Charlin, Emmanuelle; Lang, Hervé; Kurtz, Jean-Emmanuel; Imperiale, Alessio

    2016-09-01

    We report the surprising intense uptake of F-FDOPA in a right adrenal metastasis of a poorly differentiated metastatic adenocarcinoma of unknown primary mimicking a pheochromocytoma in a hemodialyzed patient with the typical Menard's triad and increased serum catecholamines. Our observation emphasizes that F-FDOPA is not a specific radiotracer for pheochromocytoma and paraganglioma investigation, although it is currently and successfully used in this clinical setting. Moreover, we underline that kidney failure may be responsible for abnormally high serum catecholamines values even in subjects without pheochromocytoma, leading to erroneous diagnostic conclusions particularly in patients with adrenal masses. PMID:27355847

  19. Radionecrosis versus disease progression in brain metastasis. Value of (18)F-DOPA PET/CT/MRI.

    PubMed

    Hernández Pinzón, J; Mena, D; Aguilar, M; Biafore, F; Recondo, G; Bastianello, M

    2016-01-01

    The use of (18)F-DOPA PET/CT with magnetic resonance imaging fusion and the use of visual methods and quantitative analysis helps to differentiate between changes post-radiosurgery vs. suspicion of disease progression in a patient with brain metastases from melanoma, thus facilitating taking early surgical action. PMID:27117985

  20. Dopaminergic correlates of metabolic network activity in Parkinson's disease.

    PubMed

    Holtbernd, Florian; Ma, Yilong; Peng, Shichun; Schwartz, Frank; Timmermann, Lars; Kracht, Lutz; Fink, Gereon R; Tang, Chris C; Eidelberg, David; Eggers, Carsten

    2015-09-01

    Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss. PMID:26037537

  1. Using kinetic parameter analysis of dynamic FDOPA-PET for brain tissue classification

    NASA Astrophysics Data System (ADS)

    Lin, Hong-Dun; Lin, Kang-Ping; Chung, Being-Tau; Yu, Chin-Lung; Wang, Rong-Fa; Wu, Liang-Chi; Liu, Ren-Shyan

    2002-04-01

    In clinically, structural image based brain tissue segmentation as a preprocess plays an important and essential role on a number of image preprocessing, such as image visualization, object recognition, image registration, and so forth. However, when we need to classify the tissues according to their physiological functions, those strategies are not satisfactory. In this study, we incorporated both tissue time-activity curves (TACs) and derived kinetic parametric curves (KPCs) information to segment brain tissues, such as striatum, gray and white matters, in dynamic FDOPA-PET studies. Four common clustering techniques, K-mean (KM), Fuzzy C-mean (FCM), Isodata (ISO), Markov Random Fields (MRF), and our method were compared to evaluate its precision. The results show 41% and 48% less mean errors in mean difference for KPCs and TACs, respectively, than other methods. Combined KPCs and TACs based clustering method provide the ability to define brain structure effectively.

  2. Comparative evaluation of 18F-FDOPA, 13N-AMMONIA, 18F-FDG PET/CT and MRI in primary brain tumors - A pilot study

    PubMed Central

    Jora, Charu; Mattakarottu, Jacob J; Aniruddha, Pandit G; Mudalsha, Ravina; Singh, Dhananjay K; Pathak, Harish C; Sharma, Nitin; Sarin, Arti; Prince, Arvind; Singh, Giriraj

    2011-01-01

    Aim: To determine the diagnostic reliability of 18F-FDOPA, 13N-Ammonia and 18F-FDG PET/CT in primary brain tumors and comparison with magnetic resonance imaging (MRI). Materials and Methods: A total of 23 patients, 8 preoperative and 15 postoperative, undergoing evaluation for primary brain tumors were included in this study. Of them, 9/15 were operated for high grade gliomas (7/9 astrocytomas and 2/9 oligodendrogliomas) and 6/15 for low grade gliomas (5/6 astrocytomas and 1/6 oligodendroglioma). After PET study, 2 of 8 preoperative cases were histopathologically proven to be of benign etiology. 3 low grade and 2 high grade postoperative cases were disease free on 6 months follow-up. Tracer uptake was quantified by standardized uptake values (SUVmax) and the SUV max ratio of tumor to normal symmetrical area of contra lateral hemisphere (T/N). 18F-FDOPA uptake was also quantified by SUVmax ratio of tumor to striatum (T/S). Conventional MR studies were done in all patients. Results: Both high-grade and low-grade tumors were well visualized with 18F-FDOPA PET. Sensitivity of 18F-FDOPA PET was substantially higher (6/6 preoperative, 3/3 low grade postoperative, 7/7 high grade postoperative) than with 18F-FDG (3/6 preoperative, 1/3 low grade postoperative, 3/7 high grade postoperative) and 13N-Ammonia PET (2/6 preoperative, 1/3 low grade postoperative, 1/7 high grade postoperative). FDOPA was equally specific as FDG and Ammonia PET in operated cases but was falsely positive in two preoperative cases. Sensitivity of FDOPA (16/16) was more than MRI (13/16). Conclusion: 18F-FDG uptake correlates with tumor grade. Though 18F-FDOPA PET cannot distinguish between tumor grade, it is more reliable than 18F-FDG and 13N-Ammonia PET for evaluating brain tumors. 18F-FDOPA PET may prove to be superior to MRI in evaluating recurrence and residual tumor tissue. 13N-Ammonia PET did not show any encouraging results. PMID:22174511

  3. 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 BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  4. 18F-FDOPA and 18F-FLT positron emission tomography parametric response maps predict response in recurrent malignant gliomas treated with bevacizumab.

    PubMed

    Harris, Robert J; Cloughesy, Timothy F; Pope, Whitney B; Nghiemphu, Phioanh L; Lai, Albert; Zaw, Taryar; Czernin, Johannes; Phelps, Michael E; Chen, Wei; Ellingson, Benjamin M

    2012-08-01

    The current study examined the use of voxel-wise changes in (18)F-FDOPA and (18)F-FLT PET uptake, referred to as parametric response maps (PRMs), to determine whether they were predictive of response to bevacizumab in patients with recurrent malignant gliomas. Twenty-four patients with recurrent malignant gliomas who underwent bevacizumab treatment were analyzed. Patients had MR and PET images acquired before and at 2 time points after bevacizumab treatment. PRMs were created by examining the percentage change in tracer uptake between time points in each image voxel. Voxel-wise increase in PET uptake in areas of pretreatment contrast enhancement defined by MRI stratified 3-month progression-free survival (PFS) and 6-month overall survival (OS) according to receiver-operating characteristic curve analysis. A decrease in PET tracer uptake was associated with longer PFS and OS, whereas an increase in PET uptake was associated with short PFS and OS. The volume fraction of increased (18)F-FDOPA PET uptake between the 2 posttreatment time points also stratified long- and short-term PFS and OS (log-rank, P < .05); however, (18)F-FLT uptake did not stratify OS. This study suggests that an increase in FDOPA or FLT PET uptake on PRMs after bevacizumab treatment may be a useful biomarker for predicting PFS and that FDOPA PET PRMs are also predictive of OS in recurrent gliomas treated with bevacizumab. PMID:22711609

  5. Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations.

    PubMed

    Wu, Ruey-Meei; Shan, Din-E; Sun, Chen-Ming; Liu, Ren-Shyan; Hwu, Wuh-Liang; Tai, Chun-Hwei; Hussey, Jennifer; West, Andrew; Gwinn-Hardy, Katrina; Hardy, John; Chen, Judy; Farrer, Matt; Lincoln, Sarah

    2002-07-01

    We report on clinical (18)F-labeled 6-fluorodopa ((18)F-dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early-onset Parkinson's disease. As described in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive-compulsive disorders were manifest. The (18)F-dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function. PMID:12210855

  6. 18F-DOPA PET/CT but not 68Ga-DOTA-TOC PET/CT revealed the underlying cause of ectopic Cushing syndrome.

    PubMed

    Schalin-Jäntti, Camilla; Ahonen, Aapo; Seppänen, Marko

    2012-09-01

    F-DOPA PET/CT but not Ga-DOTA-TOC PET/CT revealed the cause of ectopic Cushing syndrome in a 61-year-old man. The patient presented with rapid weight gain, swollen legs, and sleep disturbances. Plasma potassium level was 2.7 mM (reference range, 3.3-4.9 mM), 24-hour urinary cortisol level was 13,124 nmol (reference range, 30-144 nmol), and plasma adrenocorticotropin level was 61 ng/L (reference range, <48 g/L). CT demonstrated prominent lymph nodes in the left lung hilus and hyperplastic adrenals but no primary tumor. Ga-DOTA-TOC PET/CT, which is recommended as the first-line PET imaging, was performed, but it was not diagnostic. Imaging with F-DOPA PET/CT revealed the underlying cause. PMID:22889786

  7. 18F-DOPA Uptake of Developmental Venous Anomalies in Children With Brain Tumors.

    PubMed

    Morana, Giovanni; Piccardo, Arnoldo; Garrè, Maria Luisa; Cabria, Manlio; Rossi, Andrea

    2016-07-01

    We report the finding of increased F-3,4-dihydroxyphenylalanine uptake of the brain parenchyma adjacent to developmental venous anomalies, incidentally discovered in 3 pediatric patients with diffusely infiltrating gliomas. One patient presented 3 developmental venous anomalies located distant from the tumor, whereas in the remaining 2 patients, the vascular anomalies were inside the tumoral area mimicking a focal area of increased tumor metabolism. In the setting of brain tumor imaging, focal increased F-3,4-dihydroxyphenylalanine uptake should be carefully interpreted in light of MRI findings, and nuclear medicine physicians should be aware of any incidental minor vascular abnormality for proper interpretation of PET data. PMID:26909711

  8. High-Grade Glioma Radiation Therapy Target Volumes and Patterns of Failure Obtained From Magnetic Resonance Imaging and {sup 18}F-FDOPA Positron Emission Tomography Delineations From Multiple Observers

    SciTech Connect

    Kosztyla, Robert; Chan, Elisa K.; Hsu, Fred; Wilson, Don; Ma, Roy; Cheung, Arthur; Zhang, Susan; Moiseenko, Vitali; Benard, Francois; Nichol, Alan

    2013-12-01

    Purpose: The objective of this study was to compare recurrent tumor locations after radiation therapy with pretreatment delineations of high-grade gliomas from magnetic resonance imaging (MRI) and 3,4-dihydroxy-6-[{sup 18}F]fluoro-L-phenylalanine ({sup 18}F-FDOPA) positron emission tomography (PET) using contours delineated by multiple observers. Methods and Materials: Nineteen patients with newly diagnosed high-grade gliomas underwent computed tomography (CT), gadolinium contrast-enhanced MRI, and {sup 18}F-FDOPA PET/CT. The image sets (CT, MRI, and PET/CT) were registered, and 5 observers contoured gross tumor volumes (GTVs) using MRI and PET. Consensus contours were obtained by simultaneous truth and performance level estimation (STAPLE). Interobserver variability was quantified by the percentage of volume overlap. Recurrent tumor locations after radiation therapy were contoured by each observer using CT or MRI. Consensus recurrence contours were obtained with STAPLE. Results: The mean interobserver volume overlap for PET GTVs (42% ± 22%) and MRI GTVs (41% ± 22%) was not significantly different (P=.67). The mean consensus volume was significantly larger for PET GTVs (58.6 ± 52.4 cm{sup 3}) than for MRI GTVs (30.8 ± 26.0 cm{sup 3}, P=.003). More than 95% of the consensus recurrence volume was within the 95% isodose surface for 11 of 12 (92%) cases with recurrent tumor imaging. Ten (91%) of these cases extended beyond the PET GTV, and 9 (82%) were contained within a 2-cm margin on the MRI GTV. One recurrence (8%) was located outside the 95% isodose surface. Conclusions: High-grade glioma contours obtained with {sup 18}F-FDOPA PET had similar interobserver agreement to volumes obtained with MRI. Although PET-based consensus target volumes were larger than MRI-based volumes, treatment planning using PET-based volumes may not have yielded better treatment outcomes, given that all but 1 recurrence extended beyond the PET GTV and most were contained by a 2-cm

  9. Metabolic neuropathies

    MedlinePlus

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  10. 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 ...

  11. Metabolic Disorders

    MedlinePlus

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  12. Metabolic myopathies

    NASA Technical Reports Server (NTRS)

    Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

    1994-01-01

    Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

  13. Metabolic ecology.

    PubMed

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  14. Metabolic Syndrome

    MedlinePlus

    ... cause of metabolic syndrome. The cause might be insulin resistance. Insulin is a hormone your body produces to help ... into energy for your body. If you are insulin resistant, too much sugar builds up in your ...

  15. Metabolic Myopathies

    MedlinePlus

    ... muscles. Metabolic refers to chemical reactions that provide energy, nutrients and substances necessary for health and growth. ... occur when muscle cells don’t get enough energy. Without enough energy, the muscle lacks enough fuel ...

  16. Metabolic Syndrome

    MedlinePlus

    ... is not known but genetic factors, too much body fat (especially in the waist area, the most dangerous ... Metabolic Risk Factors Measurement Large amount of abdominal body fat Waist measurement of more than 40 inches (101 ...

  17. Metabolic microspheres

    NASA Astrophysics Data System (ADS)

    Fox, Sidney W.

    1980-08-01

    A systematic review of catalytic activities in thermal proteinoids and microspheres aggregated therefrom yields some new inferences on the origins and evolution of metabolism. Experiments suggest that, instead of being inert, protocells were already biochemically and cytophysically competent. The emergence and refinement of metabolism ab initio is thus partly traced conceptually. When the principle of molecular self-instruction, as of amino acids in peptide synthesis, is taken into account as a concomitant of natural selection, an expanded theory of organismic evolution, including saltations, emerges.

  18. Metabolic analyzer

    NASA Technical Reports Server (NTRS)

    Lem, J. D.

    1977-01-01

    The metabolic analyzer was designed to support experiment M171. It operates on the so-called open circuit method to measure a subject's metabolic activity in terms of oxygen consumed, carbon dioxide produced, minute volume, respiratory exchange ratio, and tidal volume or vital capacity. The system operates in either of two modes. (1) In Mode I, inhaled respiratory volumes are actually measured by a piston spirometer. (2) In Mode II, inhaled volumes are calculated from the exhaled volume and the measured inhaled and exhaled nitrogen concentrations. This second mode was the prime mode for Skylab. Following is a brief description of the various subsystems and their operation.

  19. Metabolic Syndrome

    MedlinePlus

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  20. Metabolic Syndrome

    MedlinePlus

    ... from Nemours for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot ... > Metabolic Syndrome Print A A A Text Size ...

  1. Metabolic Analysis

    NASA Astrophysics Data System (ADS)

    Tolstikov, Vladimir V.

    Analysis of the metabolome with coverage of all of the possibly detectable components in the sample, rather than analysis of each individual metabolite at a given time, can be accomplished by metabolic analysis. Targeted and/or nontargeted approaches are applied as needed for particular experiments. Monitoring hundreds or more metabolites at a given time requires high-throughput and high-end techniques that enable screening for relative changes in, rather than absolute concentrations of, compounds within a wide dynamic range. Most of the analytical techniques useful for these purposes use GC or HPLC/UPLC separation modules coupled to a fast and accurate mass spectrometer. GC separations require chemical modification (derivatization) before analysis, and work efficiently for the small molecules. HPLC separations are better suited for the analysis of labile and nonvolatile polar and nonpolar compounds in their native form. Direct infusion and NMR-based techniques are mostly used for fingerprinting and snap phenotyping, where applicable. Discovery and validation of metabolic biomarkers are exciting and promising opportunities offered by metabolic analysis applied to biological and biomedical experiments. We have demonstrated that GC-TOF-MS, HPLC/UPLC-RP-MS and HILIC-LC-MS techniques used for metabolic analysis offer sufficient metabolome mapping providing researchers with confident data for subsequent multivariate analysis and data mining.

  2. Can you boost your metabolism?

    MedlinePlus

    Resting metabolism rate (RMR); Total daily energy expenditure (TDEE); Non-exercise activity thermogenesis (NEAT); Weight loss - metabolism; Overweight - metabolism; Obesity - metabolism; Diet - metabolism

  3. Disorders of Lipid Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Fats (lipids) are ... carbohydrates and low in fats. Supplements of the amino acid carnitine may be helpful. The long-term outcome ...

  4. Why Metabolic Syndrome Matters

    MedlinePlus

    ... Pressure Tools & Resources Stroke More Why Metabolic Syndrome Matters Updated:Jul 24,2014 Metabolic syndrome may be ... Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • Your Risk for Metabolic Syndrome • Symptoms & Diagnosis • Prevention & ...

  5. Amino Acid Metabolism Disorders

    MedlinePlus

    ... defects & other health conditions > Amino acid metabolism disorders Amino acid metabolism disorders E-mail to a friend Please ... baby’s newborn screening may include testing for certain amino acid metabolism disorders. These are rare health conditions that ...

  6. Comprehensive metabolic panel

    MedlinePlus

    A comprehensive metabolic panel is a group of blood tests. They provide an overall picture of your body's chemical balance and metabolism. Metabolism refers to all the physical and chemical processes ...

  7. Carbohydrate Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally ...

  8. Blueberries and Metabolic Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic Syndrome is a cluster of metabolic disorders that increase the risk of cardiovascular diseases. Type 2 diabetes, elevated blood pressure, and atherogenic dyslipidemia are among the metabolic alterations that predispose the individual to several adverse cardiovascular complications. The hea...

  9. Disorders of Amino Acid Metabolism

    MedlinePlus

    ... Aspiration Syndrome Additional Content Medical News Disorders of Amino Acid Metabolism By Lee M. Sanders, MD, MPH NOTE: ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Amino acids are ...

  10. Amino Acid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup ...

  11. Inborn errors of metabolism

    MedlinePlus

    Metabolism - inborn errors of ... Bodamer OA. Approach to inborn errors of metabolism. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 205. Rezvani I, Rezvani G. An ...

  12. Lipid Metabolism Disorders

    MedlinePlus

    Metabolism is the process your body uses to make energy from the food you eat. Food is ... disorder, something goes wrong with this process. Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs ...

  13. Metabolic liver disease.

    PubMed

    McKiernan, Pat

    2012-06-01

    Diagnosis of metabolic liver disease requires a high level of diagnostic suspicion. Diet is usually the primary treatment for metabolic liver disease. Where indicated, liver transplantation provides lifelong functional correction of liver-based metabolic defects. Liver cell therapy warrants further study for the future treatment of metabolic liver disease. All families should receive genetic advice and pre-emptive management of future affected siblings. PMID:22521124

  14. Metabolic Engineering X Conference

    SciTech Connect

    Flach, Evan

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  15. Can you boost your metabolism?

    MedlinePlus

    ... activity thermogenesis (NEAT); Weight loss - metabolism; Overweight - metabolism; Obesity - metabolism; Diet - metabolism ... Cowley MA, Brown WA, Considine RV. Obesity. In: Jameson JL, De Groot ... and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; ...

  16. Epigenetics and Cancer Metabolism

    PubMed Central

    Johnson, Christelle; Warmoes, Marc O.; Shen, Xiling; Locasale, Jason W.

    2013-01-01

    Cancer cells adapt their metabolism to support proliferation and survival. A hallmark of cancer, this alteration is characterized by dysfunctional metabolic enzymes, changes in nutrient availability, tumor microenvironment and oncogenic mutations. Metabolic rewiring in cancer is tightly connected to changes at the epigenetic level. Enzymes that mediate epigenetic status of cells catalyze posttranslational modifications of DNA and histones and influence metabolic gene expression. These enzymes require metabolites that are used as cofactors and substrates to carry out reactions. This interaction of epigenetics and metabolism constitutes a new avenue of cancer biology and could lead to new insights for the development of anti-cancer therapeutics. PMID:24125862

  17. Metabolism of halophilic archaea.

    PubMed

    Falb, Michaela; Müller, Kerstin; Königsmaier, Lisa; Oberwinkler, Tanja; Horn, Patrick; von Gronau, Susanne; Gonzalez, Orland; Pfeiffer, Friedhelm; Bornberg-Bauer, Erich; Oesterhelt, Dieter

    2008-03-01

    In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic diversity of halophilic archaea was investigated at the genomic level through systematic metabolic reconstruction and comparative analysis of four completely sequenced species: Halobacterium salinarum, Haloarcula marismortui, Haloquadratum walsbyi, and the haloalkaliphile Natronomonas pharaonis. The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. The carefully assessed metabolic data represent a reliable resource for future system biology approaches as it also links to current experimental data on (halo)archaea from the literature. PMID:18278431

  18. Sustained metabolic scope.

    PubMed Central

    Peterson, C C; Nagy, K A; Diamond, J

    1990-01-01

    Sustained metabolic rates (SusMR) are time-averaged metabolic rates that are measured in free-ranging animals maintaining constant body mass over periods long enough that metabolism is fueled by food intake rather than by transient depletion of energy reserves. Many authors have suggested that SusMR of various wild animal species are only a few times resting (basal or standard) metabolic rates (RMR). We test this conclusion by analyzing all 37 species (humans, 31 other endothermic vertebrates, and 5 ectothermic vertebrates) for which SusMR and RMR had both been measured. For all species, the ratio of SusMR to RMR, which we term sustained metabolic scope, is less than 7; most values fall between 1.5 and 5. Some of these values, such as those for Tour de France cyclists and breeding birds, are surely close to sustainable metabolic ceilings for the species studied. That is, metabolic rates higher than 7 times RMR apparently cannot be sustained indefinitely. These observations pose several questions: whether the proximate physiological causes of metabolic ceilings reside in the digestive tract's ability to process food or in each tissue's metabolic capacity; whether ceiling values are independent of the mode of energy expenditure; whether ceilings are set by single limiting physiological capacities or by coadjusted clusters of capacities (symmorphosis); what the ultimate evolutionary causes of metabolic ceilings are; and how metabolic ceilings may limit animals' reproductive effort, foraging behavior, and geographic distribution. PMID:2315323

  19. Metabolic syndrome and menopause

    PubMed Central

    2013-01-01

    Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value<0.05). Our study shows high abdominal obesity and hypertension are the most prevalent components of metabolic syndrome. 15%, 13.3% and 1.8% of subjects had three, four and five criteria for metabolic syndrome, respectively. There was a significant relationship between number of components of metabolic syndrome and waist circumference. Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause. PMID:23497470

  20. Engineering Cellular Metabolism.

    PubMed

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation. PMID:26967285

  1. Inflammasomes and metabolic disease.

    PubMed

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Flavell, Richard A

    2014-01-01

    Innate immune response pathways and metabolic pathways are evolutionarily conserved throughout species and are fundamental to survival. As such, the regulation of whole-body and cellular metabolism is intimately integrated with immune responses. However, the introduction of new variables to this delicate evolutionarily conserved physiological interaction can lead to deleterious consequences for organisms as a result of inappropriate immune responses. In recent decades, the prevalence and incidence of metabolic diseases associated with obesity have dramatically increased worldwide. As a recently acquired human characteristic, obesity has exposed the critical role of innate immune pathways in multiple metabolic pathophysiological processes. Here, we review recent evidence that highlights inflammasomes as critical sensors of metabolic perturbations in multiple tissues and their role in the progression of highly prevalent metabolic diseases. PMID:24274736

  2. [Liver and drug metabolism].

    PubMed

    Mikheeva, O M

    2011-01-01

    Liver metabolism aims to change the biological activity of drugs to make them water-soluble to be excreted with bile and urine. The degree of metabolism depends on fermentative capacity for each drag (P450 fermentative system is localized in microsomal fraction of hepatocyte). Metabolism ability also changes under the influence of other substances. Liver diseases lead up to decrease of drug clirens and to increase the semi-excretion time because of reduction of liver metabolism. Therefore the drags usually undergoing intensive liver metabolism necessitate a high risk of overdose when liver diseases present. On the other hand no risk of overdose exist when drags with low liver metabolism are used. PMID:21560652

  3. Metabolic Syndrome and Migraine

    PubMed Central

    Sachdev, Amit; Marmura, Michael J.

    2012-01-01

    Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogenesis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise. PMID:23181051

  4. Metabolism, longevity and epigenetics.

    PubMed

    Cosentino, Claudia; Mostoslavsky, Raul

    2013-05-01

    Metabolic homeostasis and interventions that influence nutrient uptake are well-established means to influence lifespan even in higher eukaryotes. Until recently, the molecular mechanisms explaining such an effect remained scantily understood. Sirtuins are a group of protein deacetylases that depend on the metabolic intermediate NAD(+) as a cofactor for their function. For this reason they sense metabolic stress and in turn function at multiple levels to exert proper metabolic adaptation. Among other things, sirtuins can perform as histone deacetylases inducing epigenetic changes to modulate transcription and DNA repair. Recent studies have indicated that beyond sirtuins, the activity of other chromatin modifiers, such as histone acetyl transferases, might also be tightly linked to the availability of their intermediate metabolite acetyl-CoA. We summarize current knowledge of the emerging concepts indicating close crosstalk between the epigenetic machineries able to sense metabolic stress, their adaptive metabolic responses and their potential role in longevity. PMID:23467663

  5. METABOLISM Wnt Signaling Regulates Hepatic Metabolism

    PubMed Central

    Liu, Hongjun; Fergusson, Maria M.; Wu, J. Julie; Rovira, Ilsa I.; Liu, Jie; Gavrilova, Oksana; Lu, Teng; Bao, Jianjun; Han, Donghe; Sack, Michael N.; Finkel, Toren

    2011-01-01

    The contribution of the Wnt pathway has been extensively characterized in embryogenesis, differentiation, and stem cell biology but not in mammalian metabolism. Here, using in vivo gain- and loss-of-function models, we demonstrate an important role for Wnt signaling in hepatic metabolism. In particular, β-Catenin, the downstream mediator of canonical Wnt signaling, altered serum glucose concentrations and regulated hepatic glucose production. β-catenin also modulated hepatic insulin signaling. Furthermore, β-catenin interacted with the transcription factor FoxO1 in livers from mice under starved conditions. The interaction of FoxO1 with β-catenin regulated the transcriptional activation of the genes encoding glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), the two rate-limiting enzymes in hepatic gluconeogenesis. Moreover, starvation induced the hepatic expression of mRNAs encoding different Wnt isoforms. In addition, nutrient deprivation appeared to favor the association of β-catenin with FoxO family members, rather than with members of the T cell factor of transcriptional activators. Notably, in a model of diet-induced obesity, hepatic deletion of β-catenin improved overall metabolic homeostasis. These observations implicate Wnt signaling in the modulation of hepatic metabolism and raise the possibility that Wnt signaling may play a similar role in the metabolic regulation of other tissues. PMID:21285411

  6. Evolution of Metabolism

    NASA Astrophysics Data System (ADS)

    Nealson, K. H.; Rye, R.

    2003-12-01

    This chapter is devoted to the discussion of the evolution of metabolism, with a particular focus towards redox metabolism and the utilization of redox energy by life. We will deal with various aspects of metabolism that involve direct interaction with, and the extraction of energy from, the environment (catabolic metabolism) and will talk briefly of the reactions that affect mineral formation and dissolution. However, we will de-emphasize the aspects related to the formation of complex molecules and organisms. To some, it will be refreshingly brief; to others, somewhat superficial. This is unavoidable, as our knowledge of the details of the evolution of metabolism is at best slim. However, by piecing together aspects of the properties and history of the Earth and coupling these with what we know of today's metabolism, it is possible to at least frame several different hypotheses that, with time, should be possible to test and modify so that the next writing of this chapter might contain some intellectual entrees and not just the appetizers. Any discussion of metabolic evolution must occur in concert with a consideration of the Earth - the understanding of the forces that drove the co-evolution of life and Earth can be achieved only by considering them together. This theme will pervade this chapter, and any real understanding of the evolution of metabolism must be inexorably coupled to, and consistent with, the geological record of the Earth.The first aspect of evolution concerns the metabolic participants as we know them now (i.e., a definition of metabolic diversity), and the second concerns the sequence of events that have led to this remarkable metabolic diversity. The first part is fairly straightforward: a discussion of the domains of life, and the metabolic achievements that are expressed in the various domains, and relating metabolism to biogeochemical processes whenever possible. The second part is much more problematic. While it is possible to make up

  7. Mevalonate metabolism in cancer.

    PubMed

    Gruenbacher, Georg; Thurnher, Martin

    2015-01-28

    Cancer cells are characterized by sustained proliferative signaling, insensitivity to growth suppressors and resistance to apoptosis as well as by replicative immortality, the capacity to induce angiogenesis and to perform invasive growth. Additional hallmarks of cancer cells include the reprogramming of energy metabolism as well as the ability to evade immune surveillance. The current review focuses on the metabolic reprogramming of cancer cells and on the immune system's capacity to detect such changes in cancer cell metabolism. Specifically, we focus on mevalonate metabolism, which is a target for drug and immune based cancer treatment. PMID:24467965

  8. Eicosanoids in Metabolic Syndrome

    PubMed Central

    Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

    2013-01-01

    Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

  9. METABOLISM OF CARBAMATE INSECTICIDES

    EPA Science Inventory

    The results of studies conducted to determine the metabolic fate of carbamate insecticides and its toxicological significance are presented. Methomyl metabolism in rats was investigated in detail as was Croneton in the rat, cow, pig and chicken. Carbaryl and carbofuran were admin...

  10. Metabolic rate measurement system

    NASA Technical Reports Server (NTRS)

    Koester, K.; Crosier, W.

    1980-01-01

    The Metabolic Rate Measurement System (MRMS) is an uncomplicated and accurate apparatus for measuring oxygen consumption and carbon dioxide production of a test subject. From this one can determine the subject's metabolic rate for a variety of conditions, such as resting or light exercise. MRMS utilizes an LSI/11-03 microcomputer to monitor and control the experimental apparatus.

  11. METABOLIC PATHWAY REGULATION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research efforts in the past two decades have revealed the complex mechanisms employed by fungi to control gene activity. The tremendous expansion in our knowledge of the regulation of nitrogen metabolism and carbon metabolism, due largely to the powerful combination of genetics, biochemistry, and ...

  12. Metabolic Engineering VII Conference

    SciTech Connect

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  13. Metabolic surgery: quo vadis?

    PubMed

    Ramos-Leví, Ana M; Rubio Herrera, Miguel A

    2014-01-01

    The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed. PMID:23911576

  14. Metabolism in cancer metastasis.

    PubMed

    Weber, Georg F

    2016-05-01

    Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology. PMID:26355498

  15. Metabolic disorders in menopause

    PubMed Central

    Pertyński, Tomasz; Pertyńska-Marczewska, Magdalena

    2015-01-01

    Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM) or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women's life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases) in menopause, including the role of a tailored menopausal hormone therapy (HT). According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy). Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities. PMID:26327890

  16. Identifying Branched Metabolic Pathways by Merging Linear Metabolic Pathways

    NASA Astrophysics Data System (ADS)

    Heath, Allison P.; Bennett, George N.; Kavraki, Lydia E.

    This paper presents a graph-based algorithm for identifying complex metabolic pathways in multi-genome scale metabolic data. These complex pathways are called branched pathways because they can arrive at a target compound through combinations of pathways that split compounds into smaller ones, work in parallel with many compounds, and join compounds into larger ones. While most previous work has focused on identifying linear metabolic pathways, branched metabolic pathways predominate in metabolic networks. Automatic identification of branched pathways has a number of important applications in areas that require deeper understanding of metabolism, such as metabolic engineering and drug target identification. Our algorithm utilizes explicit atom tracking to identify linear metabolic pathways and then merges them together into branched metabolic pathways. We provide results on two well-characterized metabolic pathways that demonstrate that this new merging approach can efficiently find biologically relevant branched metabolic pathways with complex structures.

  17. Physiology of Iron Metabolism

    PubMed Central

    Waldvogel-Abramowski, Sophie; Waeber, Gérard; Gassner, Christoph; Buser, Andreas; Frey, Beat M.; Favrat, Bernard; Tissot, Jean-Daniel

    2014-01-01

    Summary A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. ‘Ironomics’ certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism. PMID:25053935

  18. [Traumatic disease and metabolism].

    PubMed

    Deriabin, I I; Nasonkin, O S; Nemchenko, N S; Gol'm, N P; Zimina, Z P

    1984-06-01

    The authors have established that the traumatic disease is accompanied by phasic nonspecific changes of metabolism correlating with the trauma severity as well as with its specific features and outcomes. Within the first 3-7 days catabolic processes are found to prevail and metabolic acidosis develop. Later, anabolic processes become activated in the non-complicated course of the disease. Normalization of most biochemical processes is accomplished within 15-21 days. More pronounced and prolonged disturbances of metabolism are observed in complications and lethal outcomes. PMID:6474706

  19. Drugs affecting glycosaminoglycan metabolism.

    PubMed

    Ghiselli, Giancarlo; Maccarana, Marco

    2016-07-01

    Glycosaminoglycans (GAGs) are charged polysaccharides ubiquitously present at the cell surface and in the extracellular matrix. GAGs are crucial for cellular homeostasis, and their metabolism is altered during pathological processes. However, little consideration has been given to the regulation of the GAG milieu through pharmacological interventions. In this review, we provide a classification of small molecules affecting GAG metabolism based on their mechanism of action. Furthermore, we present evidence to show that clinically approved drugs affect GAG metabolism and that this could contribute to their therapeutic benefit. PMID:27217160

  20. Fundamentals of cancer metabolism

    PubMed Central

    DeBerardinis, Ralph J.; Chandel, Navdeep S.

    2016-01-01

    Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

  1. Fundamentals of cancer metabolism.

    PubMed

    DeBerardinis, Ralph J; Chandel, Navdeep S

    2016-05-01

    Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

  2. Circadian Clocks and Metabolism

    PubMed Central

    Marcheva, Biliana; Ramsey, Kathryn M.; Peek, Clara B.; Affinati, Alison; Maury, Eleonore; Bass, Joseph

    2014-01-01

    Circadian clocks maintain periodicity in internal cycles of behavior, physiology, and metabolism, enabling organisms to anticipate the 24-h rotation of the Earth. In mammals, circadian integration of metabolic systems optimizes energy harvesting and utilization across the light/dark cycle. Disruption of clock genes has recently been linked to sleep disorders and to the development of cardiometabolic disease. Conversely, aberrant nutrient signaling affects circadian rhythms of behavior. This chapter reviews the emerging relationship between the molecular clock and metabolic systems and examines evidence that circadian disruption exerts deleterious consequences on human health. PMID:23604478

  3. Metabolism. Part III: Lipids.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Describes the metabolic processes of complex lipids, including saponification, activation and transport, and the beta-oxidation spiral. Discusses fatty acid degradation in regard to biochemical energy and ketone bodies. (TW)

  4. Comprehensive metabolic panel

    MedlinePlus

    ... panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... How your kidneys and liver are working Blood sugar, cholesterol, and calcium levels Sodium, potassium, and chloride ...

  5. Engineering of metabolic control

    DOEpatents

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  6. Engineering of metabolic control

    DOEpatents

    Liao, James C.

    2006-10-17

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  7. CIRCADIAN REGULATION OF METABOLISM

    PubMed Central

    Bailey, Shannon M.; Udoh, Uduak S.; Young, Martin E.

    2014-01-01

    In association with sleep/wake and fasting/feeding cycles, organisms experience dramatic oscillations in energetic demands and nutrient supply. It is therefore not surprising that various metabolic parameters, ranging from the activity status of molecular energy sensors to circulating nutrient levels, oscillate in time-of-day-dependent manners. It has become increasingly clear that rhythms in metabolic processes are not simply in response to daily environmental/behavioral influences, but are driven in part by cell autonomous circadian clocks. By synchronizing the cell with its environment, clocks modulate a host of metabolic processes in a temporally appropriate manner. The purpose of this article is to review current understanding of the interplay between circadian clocks and metabolism, in addition to the pathophysiologic consequences of disruption of this molecular mechanism, in terms of cardiometabolic disease development. PMID:24928941

  8. What is Metabolic Syndrome?

    MedlinePlus

    ... becoming more common due to a rise in obesity rates among adults. In the future, metabolic syndrome may overtake smoking as the leading risk factor for heart disease. It is possible to prevent or delay ...

  9. Arginine metabolism in asthma.

    PubMed

    Scott, Jeremy A; Grasemann, Hartmut

    2014-11-01

    Nitric oxide (NO) is important in the regulation of airway tone and airway responsiveness. Alterations in the L-arginine metabolism resulting in reduced availability of the substrate L-arginine for NO synthases, as well as the presence of NO synthase inhibitors such as asymmetric dimethylarginine, contribute to the reduced NO formation and airway dysfunction in asthma. Therapeutic interventions aiming to modulate the impaired L-arginine metabolism may help correct the enhanced airway tone and responsiveness in asthma. PMID:25282289

  10. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  11. Urea metabolism in plants.

    PubMed

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. PMID:21421389

  12. Hereditary and metabolic myelopathies.

    PubMed

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

  13. Scaling metabolic rate fluctuations.

    PubMed

    Labra, Fabio A; Marquet, Pablo A; Bozinovic, Francisco

    2007-06-26

    Complex ecological and economic systems show fluctuations in macroscopic quantities such as exchange rates, size of companies or populations that follow non-Gaussian tent-shaped probability distributions of growth rates with power-law decay, which suggests that fluctuations in complex systems may be governed by universal mechanisms, independent of particular details and idiosyncrasies. We propose here that metabolic rate within individual organisms may be considered as an example of an emergent property of a complex system and test the hypothesis that the probability distribution of fluctuations in the metabolic rate of individuals has a "universal" form regardless of body size or taxonomic affiliation. We examined data from 71 individuals belonging to 25 vertebrate species (birds, mammals, and lizards). We report three main results. First, for all these individuals and species, the distribution of metabolic rate fluctuations follows a tent-shaped distribution with power-law decay. Second, the standard deviation of metabolic rate fluctuations decays as a power-law function of both average metabolic rate and body mass, with exponents -0.352 and -1/4 respectively. Finally, we find that the distributions of metabolic rate fluctuations for different organisms can all be rescaled to a single parent distribution, supporting the existence of general principles underlying the structure and functioning of individual organisms. PMID:17578913

  14. Evolution of Metabolic Dependency

    NASA Astrophysics Data System (ADS)

    Shou, Wenying

    Microbes are often found to have lost their ability to make essential metabolites (auxotrophs) and instead rely on other individuals for these metabolites. How might metabolic dependency evolve to be so common? When microbes live inside a host (endosymbionts), amply host metabolites support auxotrophic endosymbionts. If the host transmits only a small number of endosymbionts to its offspring, then auxotrophic endosymbionts can rise to high frequency simply by chance. On the other hand, auxotrophs have also been observed in abundant free-living bacteria found in ocean water where nutrient supply is low. How might auxotrophs rise to an appreciable frequency in a large population when nutrient supply is low? We have found commonly-encountered conditions that facilitate the evolution of metabolic dependency. Metabolic interactions can in turn shape spatial organization of microbial communities (Momeni et al. (2013) eLife 2, 00230; Momeni et al. (2013) eLife 2, 00960; Estrela and Brown (2013) PLoS Comput Biol 9, e1003398; Muller et al. (2014) PNAS 111, 1037-1042). Rapid evolution of metabolic dependency can contribute to the complexity of microbial communities. Evolution of metabolic dependency.

  15. Starch Metabolism in Arabidopsis

    PubMed Central

    Streb, Sebastian; Zeeman, Samuel C.

    2012-01-01

    Starch is the major non-structural carbohydrate in plants. It serves as an important store of carbon that fuels plant metabolism and growth when they are unable to photosynthesise. This storage can be in leaves and other green tissues, where it is degraded during the night, or in heterotrophic tissues such as roots, seeds and tubers, where it is stored over longer time periods. Arabidopsis accumulates starch in many of its tissues, but mostly in its leaves during the day. It has proven to be a powerful genetic system for discovering how starch is synthesised and degraded, and new proteins and processes have been discovered. Such work has major significance for our starch crops, whose yield and quality could be improved by the application of this knowledge. Research into Arabidopsis starch metabolism has begun to reveal how its daily turnover is integrated into the rest of metabolism and adapted to the environmental conditions. Furthermore, Arabidopsis mutant lines deficient in starch metabolism have been employed as tools to study other biological processes ranging from sugar sensing to gravitropism and flowering time control. This review gives a detailed account of the use of Arabidopsis to study starch metabolism. It describes the major discoveries made and presents an overview of our understanding today, together with some as-yet unresolved questions. PMID:23393426

  16. Disorders of glutamate metabolism.

    PubMed

    Kelly, A; Stanley, C A

    2001-01-01

    The significant role the amino acid glutamate assumes in a number of fundamental metabolic pathways is becoming better understood. As a central junction for interchange of amino nitrogen, glutamate facilitates both amino acid synthesis and degradation. In the liver, glutamate is the terminus for release of ammonia from amino acids, and the intrahepatic concentration of glutamate modulates the rate of ammonia detoxification into urea. In pancreatic beta-cells, oxidation of glutamate mediates amino acid-stimulated insulin secretion. In the central nervous system, glutamate serves as an excitatory neurotransmittor. Glutamate is also the precursor of the inhibitory neurotransmittor GABA, as well as glutamine, a potential mediator of hyperammonemic neurotoxicity. The recent identification of a novel form of congenital hyperinsulinism associated with asymptomatic hyperammonemia assigns glutamate oxidation by glutamate dehydrogenase a more important role than previously recognized in beta-cell insulin secretion and hepatic and CNS ammonia detoxification. Disruptions of glutamate metabolism have been implicated in other clinical disorders, such as pyridoxine-dependent seizures, confirming the importance of intact glutamate metabolism. This article will review glutamate metabolism and clinical disorders associated with disrupted glutamate metabolism. PMID:11754524

  17. Robustness of metabolic networks

    NASA Astrophysics Data System (ADS)

    Jeong, Hawoong

    2009-03-01

    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  18. Energy and metabolism.

    PubMed

    Suarez, Raul K

    2012-10-01

    Although firmly grounded in metabolic biochemistry, the study of energy metabolism has gone well beyond this discipline and become integrative and comparative as well as ecological and evolutionary in scope. At the cellular level, ATP is hydrolyzed by energy-expending processes and resynthesized by pathways in bioenergetics. A significant development in the study of bioenergetics is the realization that fluxes through pathways as well as metabolic rates in cells, tissues, organs, and whole organisms are "system properties." Therefore, studies of energy metabolism have become, increasingly, experiments in systems biology. A significant challenge continues to be the integration of phenomena over multiple levels of organization. Body mass and temperature are said to account for most of the variation in metabolic rates found in nature. A mechanistic foundation for the understanding of these patterns is outlined. It is emphasized that evolution, leading to adaptation to diverse lifestyles and environments, has resulted in a tremendous amount of deviation from popularly accepted scaling "rules." This is especially so in the deep sea which constitutes most of the biosphere. PMID:23720257

  19. Uncovering metabolism in rhabdomyosarcoma.

    PubMed

    Monti, Eugenio; Fanzani, Alessandro

    2016-01-01

    Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes 5 different histotypes, with 2 most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies 2 major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signaling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the "state of art" of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies. PMID:26209235

  20. Metabolism of phencyclidine

    SciTech Connect

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s).

  1. Endocannabinoids and Metabolic Disorders.

    PubMed

    Gatta-Cherifi, Blandine; Cota, Daniela

    2015-01-01

    The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders. While the clinical use of the first generation of cannabinoid type 1 (CB(1)) receptor blockers has been halted due to the psychiatric side effects that their use occasioned, recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism. In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders. PMID:26408168

  2. Uncovering metabolism in rhabdomyosarcoma

    PubMed Central

    Monti, Eugenio; Fanzani, Alessandro

    2016-01-01

    Abstract Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes 5 different histotypes, with 2 most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies 2 major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signaling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the “state of art” of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies. PMID:26209235

  3. [Copper transport and metabolism].

    PubMed

    Kurasaki, Masaaki; Saito, Takeshi

    2016-07-01

    In this review, copper metabolism and transport in mammalian tissues are introduced and discussed. Firstly, the copper required amounts and LD50 levels are shown to explain the difficult balances of copper in the cells between necessity and toxicity. Furthermore, on the basis of literatures published, relationship between copper-binding metallothioneins and mechanisms for the absorption and excretion of copper or hereditary copper metabolic disorders metabolism abnormality symptom are explained. Finally it has been indicated that apoptosis induced by heavy metals, especially copper was initiated by production of reactive oxygen species and oxidative stress in the cells. To understand precise mechanism for copper homeostasis in mammalian cells, further investigation will be needed to clarify the copper behaviors in normal and abnormal situations. PMID:27455798

  4. MYC, Metabolism, and Cancer

    PubMed Central

    Stine, Zachary E.; Walton, Zandra E.; Altman, Brian J.; Hsieh, Annie L.; Dang, Chi V.

    2015-01-01

    Summary The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC’s cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy. PMID:26382145

  5. Nitrile Metabolizing Yeasts

    NASA Astrophysics Data System (ADS)

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  6. ¹⁸F-DOPA PET/computed tomography imaging.

    PubMed

    Chondrogiannis, Sotirios; Marzola, Maria Cristina; Rubello, Domenico

    2014-07-01

    18F-DOPA is a radiopharmaceutical with interesting clinical applications and promising performances in the evaluation of the integrity of dopaminergic pathways, brain tumors, NETs (especially MTCs, paragangliomas, and pheochromocytomas), and congenital hyperinsulinism. 18F-DOPA traces a very specific metabolic pathway and has a very precise biodistribution pattern. As for any radiopharmaceutical, the knowledge of the normal distribution of 18F-DOPA, its physiologic variants, and its possible pitfalls is essential for the correct interpretation of PET scans. Moreover, it is important to be aware of the potential false-positive and false-negative episodes that can occur in the various clinical settings. PMID:25030394

  7. Metabolism and Mental Illness.

    PubMed

    Sestan-Pesa, Matija; Horvath, Tamas L

    2016-02-01

    Over the past century, overwhelming evidence has emerged pointing to the hypothalamus of the central nervous system (CNS) as a crucial regulator of systemic control of metabolism, including appetite and feeding behavior. Appetite (or hunger) is a fundamental driver of survival, involving complex behaviors governed by various parts of the brain, including the cerebral cortex. Here, we provide an overview of basic metabolic principles affecting the CNS and discuss their relevance to physiological and pathological conditions of higher brain functions. These novel perspectives may well provide new insights into future research strategies to facilitate the development of novel therapies for treating mental illness. PMID:26776095

  8. Toxic and Metabolic Myelopathies.

    PubMed

    Ramalho, Joana; Nunes, Renato Hoffmann; da Rocha, Antonio José; Castillo, Mauricio

    2016-10-01

    Myelopathy describes any neurologic deficit related to the spinal cord. It is most commonly caused by its compression by neoplasms, degenerative disc disease, trauma, or infection. Less common causes of myelopathy include spinal cord tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and metabolic disorders. Conditions affecting the spinal cord must be recognized as early as possible to prevent progression that may lead to permanent disability. Biopsy is rarely performed, thus the diagnosis and management rely on patient׳s history, physical examination, laboratory results, and imaging findings. Here we review the clinical presentations, pathophysiological mechanisms, and magnetic resonance imaging findings of myelopathies related to metabolic or toxic etiologies. PMID:27616316

  9. Oxidative Metabolism in Muscle

    NASA Astrophysics Data System (ADS)

    Ferrari, M.; Binzoni, T.; Quaresima, V.

    1997-06-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near-infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.

  10. Sleep and Metabolism: An Overview

    PubMed Central

    Sharma, Sunil; Kavuru, Mani

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism. PMID:20811596

  11. Metabolism at Evolutionary Optimal States

    PubMed Central

    Rabbers, Iraes; van Heerden, Johan H.; Nordholt, Niclas; Bachmann, Herwig; Teusink, Bas; Bruggeman, Frank J.

    2015-01-01

    Metabolism is generally required for cellular maintenance and for the generation of offspring under conditions that support growth. The rates, yields (efficiencies), adaptation time and robustness of metabolism are therefore key determinants of cellular fitness. For biotechnological applications and our understanding of the evolution of metabolism, it is necessary to figure out how the functional system properties of metabolism can be optimized, via adjustments of the kinetics and expression of enzymes, and by rewiring metabolism. The trade-offs that can occur during such optimizations then indicate fundamental limits to evolutionary innovations and bioengineering. In this paper, we review several theoretical and experimental findings about mechanisms for metabolic optimization. PMID:26042723

  12. METABOLISM AND METABOLIC ACTIVATION OF CHEMICALS: IN-SILICO SIMULATION

    EPA Science Inventory

    The role of metabolism in prioritizing chemicals according to their potential adverse health effects is extremely important because innocuous parents can be transformed into toxic metabolites. This work presents the TIssue MEtabolism Simulator (TIMES) platform for simulating met...

  13. Starch metabolism in leaves.

    PubMed

    Orzechowski, Sławomir

    2008-01-01

    Starch is the most abundant storage carbohydrate produced in plants. The initiation of transitory starch synthesis and degradation in plastids depends mainly on diurnal cycle, post-translational regulation of enzyme activity and starch phosphorylation. For the proper structure of starch granule the activities of all starch synthase isoenzymes, branching enzymes and debranching enzymes are needed. The intensity of starch biosynthesis depends mainly on the activity of AGPase (adenosine 5'-diphosphate glucose pyrophosphorylase). The key enzymes in starch degradation are beta-amylase, isoamylase 3 and disproportionating enzyme. However, it should be underlined that there are some crucial differences in starch metabolism between heterotrophic and autotrophic tissues, e.g. is the ability to build multiprotein complexes responsible for biosynthesis and degradation of starch granules in chloroplasts. The observed huge progress in understanding of starch metabolism was possible mainly due to analyses of the complete Arabidopsis and rice genomes and of numerous mutants with altered starch metabolism in leaves. The aim of this paper is to review current knowledge on transient starch metabolism in higher plants. PMID:18787712

  14. Lipoprotein(a) metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein. The metabolism of this lipoprotein is still not well understood. It has long been known that the plasma concentration of Lp(a) is highly heritable, with its genetic determinants located in the apo(a) locus and regulating the rate of hepatic apo(a...

  15. Metabolic breath analyzer

    NASA Technical Reports Server (NTRS)

    Perry, C. L.

    1971-01-01

    Instrument measures metabolic breathing rate and dynamics of human beings in atmospheres ranging from normal air to 100 percent oxygen at ambient pressures from 14.7 to 3.0 psia. Measurements are made at rest or performing tasks up to maximum physical capacity under either zero or normal gravity.

  16. Metabolic engineering of bacteria.

    PubMed

    Kumar, Ravi R; Prasad, Satish

    2011-07-01

    Yield and productivity are critical for the economics and viability of a bioprocess. In metabolic engineering the main objective is the increase of a target metabolite production through genetic engineering. Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the production of a certain substance. In the last years, the development of recombinant DNA technology and other related technologies has provided new tools for approaching yields improvement by means of genetic manipulation of biosynthetic pathway. Industrial microorganisms like Escherichia coli, Actinomycetes, etc. have been developed as biocatalysts to provide new or to optimize existing processes for the biotechnological production of chemicals from renewable plant biomass. The factors like oxygenation, temperature and pH have been traditionally controlled and optimized in industrial fermentation in order to enhance metabolite production. Metabolic engineering of bacteria shows a great scope in industrial application as well as such technique may also have good potential to solve certain metabolic disease and environmental problems in near future. PMID:22754024

  17. Breathing-metabolic simulator

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G.; Hendricks, C. M.; Morison, W. B.

    1972-01-01

    Breathing-metabolic simulator was developed to be used for evaluation of life support equipment. Apparatus simulates human breathing rate and controls temperature and humidity of exhaled air as well as its chemical composition. All functions are designed to correspond to various degrees of human response.

  18. Estuarine Total Ecosystem Metabolism

    EPA Science Inventory

    Total ecosystem metabolism (TEM), both as discrete measurements and as a theoretical concept, has an important history in ecosystem ecology, particularly in estuaries. Some of the earliest ecological studies were developed to determine how energy flowed through an ecosystem and w...

  19. Alcoholic metabolic emergencies.

    PubMed

    Allison, Michael G; McCurdy, Michael T

    2014-05-01

    Ethanol intoxication and ethanol use are associated with a variety of metabolic derangements encountered in the Emergency Department. In this article, the authors discuss alcohol intoxication and its treatment, dispel the myth that alcohol intoxication is associated with hypoglycemia, comment on electrolyte derangements and their management, review alcoholic ketoacidosis, and end with a section on alcoholic encephalopathy. PMID:24766933

  20. Complexity of dopamine metabolism

    PubMed Central

    2013-01-01

    Parkinson’s disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability. In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD. PMID:23683503

  1. Glyphosate metabolism in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many soil microbes and plant species metabolically degrade the herbicide glyphosate. The primary degradation routes are by a glyphosate oxidoreductase (GOX) to form aminomethylphosphonic acid (AMPA) as the distinctive metabolite and by a C-P lyase that forms sarcosine as a main metabolite. AMPA app...

  2. Metabolism of trichloroethylene.

    PubMed Central

    Lash, L H; Fisher, J W; Lipscomb, J C; Parker, J C

    2000-01-01

    A major focus in the study of metabolism and disposition of trichloroethylene (TCE) is to identify metabolites that can be used reliably to assess flux through the various pathways of TCE metabolism and to identify those metabolites that are causally associated with toxic responses. Another important issue involves delineation of sex- and species-dependent differences in biotransformation pathways. Defining these differences can play an important role in the utility of laboratory animal data for understanding the pharmacokinetics and pharmacodynamics of TCE in humans. Sex-, species-, and strain-dependent differences in absorption and distribution of TCE may play some role in explaining differences in metabolism and susceptibility to toxicity from TCE exposure. The majority of differences in susceptibility, however, are likely due to sex-, species-, and strain-dependent differences in activities of the various enzymes that can metabolize TCE and its subsequent metabolites. An additional factor that plays a role in human health risk assessment for TCE is the high degree of variability in the activity of certain enzymes. TCE undergoes metabolism by two major pathways, cytochrome P450 (P450)-dependent oxidation and conjugation with glutathione (GSH). Key P450-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include chloral hydrate, trichloroacetate, and dichloroacetate. Metabolites derived from the GSH conjugate of TCE, in contrast, have been associated with the kidney as a target organ. Specifically, metabolism of the cysteine conjugate of TCE by the cysteine conjugate ss-lyase generates a reactive metabolite that is nephrotoxic and may be nephrocarcinogenic. Although the P450 pathway is a higher activity and higher affinity pathway than the GSH conjugation pathway, one should not automatically conclude that the latter pathway is only important at very high doses. A synthesis of this information is then

  3. Dysregulated metabolism contributes to oncogenesis.

    PubMed

    Hirschey, Matthew D; DeBerardinis, Ralph J; Diehl, Anna Mae E; Drew, Janice E; Frezza, Christian; Green, Michelle F; Jones, Lee W; Ko, Young H; Le, Anne; Lea, Michael A; Locasale, Jason W; Longo, Valter D; Lyssiotis, Costas A; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P; Pedersen, Peter L; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C; Sivanand, Sharanya; Vander Heiden, Matthew G; Wellen, Kathryn E

    2015-12-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  4. Hypoxamirs and Mitochondrial Metabolism

    PubMed Central

    Cottrill, Katherine A.; Chan, Stephen Y.

    2014-01-01

    Abstract Significance: Chronic hypoxia can drive maladaptive responses in numerous organ systems, leading to a multitude of chronic mammalian diseases. Oxygen homeostasis is intimately linked with mitochondrial metabolism, and dysfunction in these systems can combine to form the backbone of hypoxic-ischemic injury in multiple tissue beds. Increased appreciation of the crucial roles of hypoxia-associated miRNA (hypoxamirs) in metabolism adds a new dimension to our understanding of the regulation of hypoxia-induced disease. Recent Advances: Myriad factors related to glycolysis (e.g., aldolase A and hexokinase II), tricarboxylic acid cycle function (e.g., glutaminase and iron-sulfur cluster assembly protein 1/2), and apoptosis (e.g., p53) have been recently implicated as targets of hypoxamirs. In addition, several hypoxamirs have been implicated in the regulation of the master transcription factor of hypoxia, hypoxia-inducible factor-1α, clarifying how the cellular program of hypoxia is sustained and resolved. Critical Issues: Central to the discussion of metabolic change in hypoxia is the Warburg effect, a shift toward anaerobic metabolism that persists after normal oxygen levels have been restored. Many newly discovered targets of hypoxia-driven microRNA converge on pathways known to be involved in this pathological phenomenon and the apoptosis-resistant phenotype associated with it. Future Directions: The often synergistic functions of miRNA may make them ideal therapeutic targets. The use of antisense inhibitors is currently being considered in diseases in which hypoxia and metabolic dysregulation predominate. In addition, exploration of pleiotripic miRNA functions will likely continue to offer unique insights into the mechanistic relationships of their downstream target pathways and associated hypoxic phenotypes. Antioxid. Redox Signal. 21, 1189–1201. PMID:24111795

  5. Cellular compartmentalization of secondary metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

  6. MedlinePlus: Metabolic Panel

    MedlinePlus

    ... Spanish Comprehensive Metabolic Panel (American Association for Clinical Chemistry) Topic Image MedlinePlus Email Updates Get Metabolic Panel updates by email What's this? GO GO National Institutes of Health The primary NIH organization for research on Metabolic Panel is the National Heart, Lung, ...

  7. Endothelial cell metabolism: parallels and divergences with cancer cell metabolism

    PubMed Central

    2014-01-01

    The stromal vasculature in tumors is a vital conduit of nutrients and oxygen for cancer cells. To date, the vast majority of studies have focused on unraveling the genetic basis of vessel sprouting (also termed angiogenesis). In contrast to the widely studied changes in cancer cell metabolism, insight in the metabolic regulation of angiogenesis is only just emerging. These studies show that metabolic pathways in endothelial cells (ECs) importantly regulate angiogenesis in conjunction with genetic signals. In this review, we will highlight these emerging insights in EC metabolism and discuss them in perspective of cancer cell metabolism. While it is generally assumed that cancer cells have unique metabolic adaptations, not shared by healthy non-transformed cells, we will discuss parallels and highlight differences between endothelial and cancer cell metabolism and consider possible novel therapeutic opportunities arising from targeting both cancer and endothelial cells. PMID:25250177

  8. Nuclear Sphingolipid Metabolism

    PubMed Central

    Lucki, Natasha C.; Sewer, Marion B.

    2014-01-01

    Nuclear lipid metabolism is implicated in various processes, including transcription, splicing, and DNA repair. Sphingolipids play roles in numerous cellular functions, and an emerging body of literature has identified roles for these lipid mediators in distinct nuclear processes. Different sphingolipid species are localized in various subnuclear domains, including chromatin, the nuclear matrix, and the nuclear envelope, where sphingolipids exert specific regulatory and structural functions. Sphingomyelin, the most abundant nuclear sphingolipid, plays both structural and regulatory roles in chromatin assembly and dynamics in addition to being an integral component of the nuclear matrix. Sphingosine-1-phosphate modulates histone acetylation, sphingosine is a ligand for steroidogenic factor 1, and nuclear accumulation of ceramide has been implicated in apoptosis. Finally, nuclear membrane–associated ganglioside GM1 plays a pivotal role in Ca2+ homeostasis. This review highlights research on the factors that control nuclear sphingolipid metabolism and summarizes the roles of these lipids in various nuclear processes. PMID:21888508

  9. Genetics of metabolic resistance.

    PubMed

    Richter, Otto; Langemann, Dirk; Beffa, Roland

    2016-09-01

    Herbicide resistance has become a major issue for many weeds. Metabolic resistance refers to the biochemical processes within organisms that degrade herbicides to less toxic compounds, resulting in a shift of the dose response curve. This type of resistance involves polygenic inheritance. A model is presented linking the biochemical pathway of amino acid synthesis and the detoxifying pathway of an inhibitor of the key enzyme ALS. From this model, resistance factors for each biotype are derived, which are then applied to a polygenic population genetic model for an annual weed plant. Polygenic inheritance is described by a new approach based on tensor products of heredity matrices. Important results from the model are that low dose regimes favour fast emergence of resistant biotypes and that the emergence of resistant biotypes occurs as abrupt outbreaks. The model is used to evaluate strategies for the management of metabolic resistance. PMID:27424952

  10. Breathing metabolic simulator

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G.; Hendricks, C. M.; Morison, W. B.

    1972-01-01

    The development of a breathing metabolic simulator (BMS) is reported. This BMS simulates all of the breathing and metabolic parameters required for complete evaluation and test of life support and resuscitation equipment. It is also useful for calibrating and validating mechanical and gaseous pulmonary function test procedures. Breathing rate, breathing depth, breath velocity contour, oxygen uptake, and carbon dioxide release are all variable over wide ranges simulating conditions from sleep to hard work with respiratory exchange ratios covering the range from hypoventilation. In addition, all of these parameters are remotely controllable to facilitate use of the device in hostile or remote environments. The exhaled breath is also maintained at body temperature and a high humidity. The simulation is accurate to the extent of having a variable functional residual capacity independent of other parameters.

  11. Surfactant phospholipid metabolism.

    PubMed

    Agassandian, Marianna; Mallampalli, Rama K

    2013-03-01

    Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. PMID:23026158

  12. Ovarian metabolism of xenobiotics.

    PubMed

    Bhattacharya, Poulomi; Keating, Aileen F

    2011-07-01

    At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4-vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described. PMID:21616964

  13. Ovarian metabolism of xenobiotics

    PubMed Central

    Bhattacharya, Poulomi; Keating, Aileen F

    2013-01-01

    At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4-vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described. PMID:21616964

  14. Teratogen metabolism. Final report

    SciTech Connect

    Braun, A.G.

    1983-01-31

    This study indicates Thalidomide is metabolized by a classic cytochrome P450 monoxygenase system to a product which inhibits attachment of cells to concanavalin A coated dishes. Hydrolysis products of Thalidomide and its active metabolite do not inhibit attachement. We have initiated additional studies with methylene chloride extracts of particulate and of volatile hydrocarbon emissions of a domestic oil burner. These studies show low levels of inhibitory activity are uniformly present in these extracts.

  15. Autophagy, Metabolism, and Cancer.

    PubMed

    White, Eileen; Mehnert, Janice M; Chan, Chang S

    2015-11-15

    Macroautophagy (autophagy hereafter) captures intracellular proteins and organelles and degrades them in lysosomes. The degradation breakdown products are released from lysosomes and recycled into metabolic and biosynthetic pathways. Basal autophagy provides protein and organelle quality control by eliminating damaged cellular components. Starvation-induced autophagy recycles intracellular components into metabolic pathways to sustain mitochondrial metabolic function and energy homeostasis. Recycling by autophagy is essential for yeast and mammals to survive starvation through intracellular nutrient scavenging. Autophagy suppresses degenerative diseases and has a context-dependent role in cancer. In some models, cancer initiation is suppressed by autophagy. By preventing the toxic accumulation of damaged protein and organelles, particularly mitochondria, autophagy limits oxidative stress, chronic tissue damage, and oncogenic signaling, which suppresses cancer initiation. This suggests a role for autophagy stimulation in cancer prevention, although the role of autophagy in the suppression of human cancer is unclear. In contrast, some cancers induce autophagy and are dependent on autophagy for survival. Much in the way that autophagy promotes survival in starvation, cancers can use autophagy-mediated recycling to maintain mitochondrial function and energy homeostasis to meet the elevated metabolic demand of growth and proliferation. Thus, autophagy inhibition may be beneficial for cancer therapy. Moreover, tumors are more autophagy-dependent than normal tissues, suggesting that there is a therapeutic window. Despite these insights, many important unanswered questions remain about the exact mechanisms of autophagy-mediated cancer suppression and promotion, how relevant these observations are to humans, and whether the autophagy pathway can be modulated therapeutically in cancer. See all articles in this CCR Focus section, "Cell Death and Cancer Therapy." PMID:26567363

  16. Automated Microbial Metabolism Laboratory

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Development of the automated microbial metabolism laboratory (AMML) concept is reported. The focus of effort of AMML was on the advanced labeled release experiment. Labeled substrates, inhibitors, and temperatures were investigated to establish a comparative biochemical profile. Profiles at three time intervals on soil and pure cultures of bacteria isolated from soil were prepared to establish a complete library. The development of a strategy for the return of a soil sample from Mars is also reported.

  17. Diseases of Phenylalanine Metabolism

    PubMed Central

    Parker, Charles E.

    1979-01-01

    Continuing investigation of the system that hydroxylates phenylalanine to tyrosine has led to new insights into diseases associated with the malfunction of this system. Good evidence has confirmed that phenylketonuria (PKU) is not caused by a simple lack of phenylalanine hydroxylase. Dihydropteridine reductase deficiency as well as defects in biopterin metabolism may also cause the clinical features of phenylketonuria. Furthermore, these diseases do not respond to the standard treatment for phenylketonuria. PMID:388868

  18. Low Spillage Metabolic Feeder

    NASA Technical Reports Server (NTRS)

    Evans, JuliAnn (Inventor); Gundo, Daniel P. (Inventor); Harper, Jennifer S. (Inventor); Mulenburg, Gerald M. (Inventor); Skundberg, Thomas L. (Inventor)

    1996-01-01

    An animal feeder for use in a metabolic cage is introduced. The feeder includes a confined passageway and an adjustable notched gate proceeding a food cup. The gate is adjusted so that the entry area to the food cup approximates the cross sectional head area of the animal. Food ejected from the food cup by a caged animal is dropped through a grate into a spill tray.

  19. Metabolic neuropathies and myopathies.

    PubMed

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. PMID:23622366

  20. Stress, Metabolism and Cancer

    PubMed Central

    Repasky, Elizabeth A.; Eng, Jason; Hylander, Bonnie L.

    2015-01-01

    The potential for immune cells to control cancers has been recognized for many decades, but only recently has real excitement begun to spread through the oncology community following clear evidence that therapeutic blockade of specific immune-suppressive mechanisms is enough to make a real difference in survival for patients with several different advanced cancers. However, impressive and encouraging as these new clinical data are, it is clear that more effort should be devoted toward understanding the full spectrum of factors within cancer patients, which have the potential to block or weaken antitumor activity by immune cells. The goal of this brief review is to highlight recent literature revealing interactive stress and metabolic pathways, particularly those mediated by the sympathetic nervous system, which may conspire to block immune cells from unleashing their full killing potential. There is exciting new information regarding the role of neurogenesis by tumors and adrenergic signaling in cancer progression (including metabolic changes associated with cachexia and lipolysis) and in regulation of immune cell function and differentiation. However, much more work is needed to fully understand how the systemic metabolic effects mediated by the brain and nervous system can be targeted for therapeutic efficacy in the setting of immunotherapy and other cancer therapies. PMID:25815849

  1. Metabolic Physiology in Pregnancy.

    PubMed

    Meo, Sultan Ayoub; Hassain, Asim

    2016-09-01

    The metabolic physiology during pregnancy is unique in the life of women. This change is a normal physiological adaptation to better accommodate the foetal growth and provides adequate blood, nutrition and oxygen. The metabolic changes prepare the mother\\'s body for pregnancy, childbirth and lactation. Early gestational period is considered as an anabolic phase, in which female body stores nutrients, enhance insulin sensitivity to encounter the maternal and feto-placental demands of late gestation and lactation. However, late gestational period is better named as a catabolic phase with reduced insulin sensitivity. The placenta plays a role as a sensor between mother and foetus physiology and acclimatizes the needs of the foetus to adequate growth and development. During pregnancy the female body changes its physiological and homeostatic mechanisms to meet the physiological needs of the foetus. However, if the maternal metabolic physiology during pregnancy is disturbed, it can cause hormonal imbalance, fat accumulation, decreased insulin sensitivity, increased insulin resistance and even gestational diabetes mellitus. PMID:27582161

  2. Metabolic response to exercise.

    PubMed

    De Feo, P; Di Loreto, C; Lucidi, P; Murdolo, G; Parlanti, N; De Cicco, A; Piccioni, F; Santeusanio, F

    2003-09-01

    At the beginning, the survival of humans was strictly related to their physical capacity. There was the need to resist predators and to provide food and water for life. Achieving these goals required a prompt and efficient energy system capable of sustaining either high intensity or maintaining prolonged physical activity. Energy for skeletal muscle contraction is supplied by anaerobic and aerobic metabolic pathways. The former can allow short bursts of intense physical activity (60-90 sec) and utilizes as energetic source the phosphocreatine shuttle and anaerobic glycolysis. The aerobic system is the most efficient ATP source for skeletal muscle. The oxidative phosporylation of carbohydrates, fats and, to a minor extent, proteins, can sustain physical activity for many hours. Carbohydrates are the most efficient fuel for working muscle and their contribution to total fuel oxidation is positively related to the intensity of exercise. The first metabolic pathways of carbohydrate metabolism to be involved are skeletal muscle glycogenolysis and glycolysis. Later circulating glucose, formed through activated gluconeogenesis, becomes an important energetic source. Among glucose metabolites, lactate plays a primary role as either direct or indirect (gluconeogenesis) energy source for contracting skeletal muscle. Fat oxidation plays a primary role during either low-moderate intensity exercise or protracted physical activity (over 90-120 min). Severe muscle glycogen depletion results in increased rates of muscle proteolysis and branched chain amino acid oxidation. Endurance training ameliorates physical performance by improving cardiopulmonary efficiency and optimizing skeletal muscle supply and oxidation of substrates. PMID:14964437

  3. METABOLISM OF IRON STORES

    PubMed Central

    SAITO, HIROSHI

    2014-01-01

    ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since the pioneering research by Shoden in 1953. However, we recently developed a new method for determining ferritin iron and hemosiderin iron by computer-assisted serum ferritin kinetics. Serum ferritin increase or decrease curves were measured in patients with normal storage iron levels (chronic hepatitis C and iron deficiency anemia treated by intravenous iron injection), and iron overload (hereditary hemochromatosis and transfusion dependent anemia). We thereby confirmed the existence of two iron pathways where iron flows followed the numbered order (1) labile iron, (2) ferritin and (3) hemosiderin in iron deposition and mobilization among many previously proposed but mostly unproven routes. We also demonstrated the increasing and decreasing phases of ferritin iron and hemosiderin iron in iron deposition and mobilization. The author first demonstrated here the change in proportion between pre-existing ferritin iron and new ferritin iron synthesized by removing iron from hemosiderin in the course of iron removal. In addition, the author disclosed the cause of underestimation of storage iron turnover rate which had been reported by previous investigators in estimating storage iron turnover rate of normal subjects. PMID:25741033

  4. Analytics for Metabolic Engineering

    PubMed Central

    Petzold, Christopher J.; Chan, Leanne Jade G.; Nhan, Melissa; Adams, Paul D.

    2015-01-01

    Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants, while deep omics analysis provides a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research. PMID:26442249

  5. Maternal cardiac metabolism in pregnancy.

    PubMed

    Liu, Laura X; Arany, Zolt

    2014-03-15

    Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal 'invasion' profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

  6. Tumor Metabolism of Malignant Gliomas

    PubMed Central

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation. PMID:24217114

  7. Metabolic pathology of autism in relation to redox metabolism.

    PubMed

    Frye, Richard E; James, S Jill

    2014-01-01

    An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorder (ASD). Glutathione synthesis and intracellular redox balance are linked to folate and methylation metabolism, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct ASD endophenotype that is closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Biomarkers that reflect these metabolic abnormalities will be discussed in the context of an ASD metabolic endophenotype that may lead to a better understanding of the pathophysiological mechanisms underlying core and associated ASD symptoms. Last, we discuss how these biomarkers have been used to guide the development of novel ASD treatments. PMID:24712422

  8. Metabolic and Cardiovascular Implications of a Metabolically Healthy Obesity Phenotype

    PubMed Central

    Seo, Mi Hae

    2014-01-01

    Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases. PMID:25559571

  9. Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications.

    PubMed

    Wu, Gang; Yan, Qiang; Jones, J Andrew; Tang, Yinjie J; Fong, Stephen S; Koffas, Mattheos A G

    2016-08-01

    Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses to metabolic burdens, as well as strategies to identify and resolve the carbon and energy burden problems, including metabolic balancing, enhancing respiration, dynamic regulatory systems, chromosomal engineering, decoupling cell growth with production phases, and co-utilization of nutrient resources. To design robust strains with high chances of success in industrial settings, novel genome-scale models (GSMs), (13)C-metabolic flux analysis (MFA), and machine-learning approaches are needed for weighting, standardizing, and predicting metabolic costs. PMID:26996613

  10. Inositol Metabolism in Plants

    PubMed Central

    Kroh, M.; Miki-Hirosige, H.; Rosen, W.; Loewus, F.

    1970-01-01

    When detached flowers or isolated pistils of Lilium longiflorum are given myoinositol-U-14C or -2-3H as dilute solution through the severed pedicel, label is quickly distributed by the vascular system. In the case of pistils, a pattern of labeling in ovary, style, and stigma is obtained which indicates that products of myoinositol metabolism are utilized in the biosynthesis of exudate (secretion product) of the stigma and style as well as for components of pistil cell walls. Pollination had no discernible effect on labeling pattern. Images PMID:5436329

  11. Breathing metabolic simulator.

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G., Jr.; Hendricks, C. M.; Morison, W. B.

    1971-01-01

    Description of a device for simulation of the human breathing and metabolic parameters required for the evaluation of respiratory diagnostic, monitoring, support and resuscitation equipment. The remotely controlled device allows wide variations in breathing rate and depth, breath velocity contour, oxygen uptake and carbon dioxide release to simulate conditions from sleep to hard work, with respiration exchange ratios ranging from hypoventilation to hyperventilation. It also reduces the cost of prolonged testing when simulation chambers with human subjects require three shifts of crews and standby physicians. Several block diagrams of the device and subsystems are given.

  12. Connecting Myokines and Metabolism

    PubMed Central

    Park, Hyeong-Kyu

    2015-01-01

    Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets. PMID:26248861

  13. Niche metabolism in parasitic protozoa

    PubMed Central

    Ginger, Michael L

    2005-01-01

    Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generated in silico has been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism. PMID:16553311

  14. [Heme metabolism and oxidative stress].

    PubMed

    Kaliman, P A; Barannik, T B

    2001-01-01

    The role of heme metabolism in oxidative stress development and defense reactions formation in mammals under different stress factors are discussed in the article. Heme metabolism is considered as the totality of synthesis, degradation, transport and exchange processes of exogenous heme and heme liberated from erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data presented display normal heme metabolism including mammals heme-binding proteins and intracellular free heme pool and heme metabolism alterations under oxidative stress development. The main attention is focused to the prooxidant action of heme, the interaction of heme transport and lipid exchange, and to the heme metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum heme-binding protein hemopexin and intracellular heme-binding proteins participating in metabolism adaptation under the action of factors, which cause oxidative stress. PMID:11599427

  15. [Metabolic bone disease osteomalacia].

    PubMed

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases. PMID:24811356

  16. Arginine metabolism in wounds

    SciTech Connect

    Albina, J.E.; Mills, C.D.; Barbul, A.; Thirkill, C.E.; Henry, W.L. Jr.; Mastrofrancesco, B.; Caldwell, M.D.

    1988-04-01

    Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of (guanido-/sup 14/C)arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis.

  17. Metabolic regulation of yeast

    NASA Astrophysics Data System (ADS)

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  18. Metabolic Syndrome: Hyperlipidemia.

    PubMed

    Bragg, Dee Ann Stults; Walling, Anne

    2015-08-01

    Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). PMID:26280341

  19. T cell metabolism drives immunity

    PubMed Central

    Buck, Michael D.; O’Sullivan, David

    2015-01-01

    Lymphocytes must adapt to a wide array of environmental stressors as part of their normal development, during which they undergo a dramatic metabolic remodeling process. Research in this area has yielded surprising findings on the roles of diverse metabolic pathways and metabolites, which have been found to regulate lymphocyte signaling and influence differentiation, function and fate. In this review, we integrate the latest findings in the field to provide an up-to-date resource on lymphocyte metabolism. PMID:26261266

  20. Teratogenic inborn errors of metabolism.

    PubMed Central

    Leonard, J. V.

    1986-01-01

    Most children with inborn errors of metabolism are born healthy without malformations as the fetus is protected by the metabolic activity of the placenta. However, certain inborn errors of the fetus have teratogenic effects although the mechanisms responsible for the malformations are not generally understood. Inborn errors in the mother may also be teratogenic. The adverse effects of these may be reduced by improved metabolic control of the biochemical disorder. PMID:3540927

  1. Regulatory Biology: Depressed Metabolic States

    NASA Technical Reports Server (NTRS)

    Holton, E. M. (Editor)

    1973-01-01

    Exobiological aspects of depressed metabolism and thermoregulation are discussed for subsequent development of biological space flight experiments. Included is a brief description of differential hypothermia in cancer chemotherapy.

  2. Metabolic Phenotypes in Pancreatic Cancer

    PubMed Central

    Yu, Min; Zhou, Quanbo; Zhou, Yu; Fu, Zhiqiang; Tan, Langping; Ye, Xiao; Zeng, Bing; Gao, Wenchao; Zhou, Jiajia; Liu, Yimin; Li, Zhihua; Lin, Ye; Lin, Qing; Chen, Rufu

    2015-01-01

    Introduction The aim of present study was to profile the glucose-dependent and glutamine- dependent metabolism in pancreatic cancer. Methods We performed Immunohistochemical staining of GLUT1, CAIX, BNIP3, p62, LC3, GLUD1, and GOT1. Based on the expression of metabolism-related proteins, the metabolic phenotypes of tumors were classified into two categories, including glucose- and glutamine-dependent metabolism. There were Warburg type, reverse Warburg type, mixed type, and null type in glucose-dependent metabolism, and canonical type, non-canonical type, mixed type, null type in glutamine-dependent metabolism. Results Longer overall survival was associated with high expression of BNIP3 in tumor (p = 0.010). Shorter overall survival was associated with high expression of GLUT1 in tumor (P = 0.002) and GOT1 in tumor (p = 0.030). Warburg type of glucose-dependent metabolism had a highest percentage of tumors with nerve infiltration (P = 0.0003), UICC stage (P = 0.0004), and activated autophagic status in tumor (P = 0.0167). Mixed type of glucose-dependent metabolism comprised the highest percentage of tumors with positive marginal status (P<0.0001), lymphatic invasion (P<0.0001), and activated autophagic status in stroma (P = 0.0002). Mixed type and Warburg type had a significant association with shorter overall survival (P = 0.018). Non-canonical type and mixed type of glutamine-dependent metabolism comprised the highest percentage of tumors with vascular invasion (p = 0.0073), highest percentage of activated autophagy in tumors (P = 0.0034). Moreover, these two types of glutamine-dependent metabolism were significantly associated with shorter overall survival (P<0.001). Further analysis suggested that most of tumors were dependent on both glucose- and glutamine-dependent metabolism. After dividing the tumors according to the number of metabolism, we found that the increasing numbers of metabolism subtypes inversely associated with survival outcome. Conclusion

  3. Drug-Induced Metabolic Acidosis

    PubMed Central

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  4. Mammalian Sirtuins and Energy Metabolism

    PubMed Central

    Li, Xiaoling; Kazgan, Nevzat

    2011-01-01

    Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. PMID:21614150

  5. Metabolic Adaptation to Muscle Ischemia

    NASA Technical Reports Server (NTRS)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  6. Drug-Induced Metabolic Acidosis.

    PubMed

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics. PMID:26918138

  7. Gut Microbiota and Metabolic Disorders.

    PubMed

    Hur, Kyu Yeon; Lee, Myung-Shik

    2015-06-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

  8. Cerebral metabolic adaptation and ketone metabolism after brain injury

    PubMed Central

    Prins, Mayumi L

    2010-01-01

    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the ‘post-weaned/adult’ brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain’s capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation. PMID:17684514

  9. Metabolism of Monoterpenes 12

    PubMed Central

    Martinkus, Charlott; Croteau, Rodney

    1981-01-01

    Previous studies have shown that the monoterpene ketone l-[G-3H]-menthone is reduced to the epimeric alcohols l-menthol and d-neomenthol in leaf discs of flowering peppermint (Mentha piperita L.), and that a portion of the menthol is converted to menthyl acetate while the bulk of the neomenthol is transformed to neomenthyl-β-d-glucoside (Croteau, Martinkus 1979 Plant Physiol 64: 169-175). The metabolic disposition of the epimeric reduction products of the ketone, which is a major constituent of peppermint oil, is highly specific, in that little neomenthyl acetate and little menthyl glucoside are formed. However, when l-[3-3H]menthol and d-[3-3H]neomenthol are separately administered to leaf discs, both menthyl and neomenthyl acetates and menthyl and neomenthyl glucosides are formed with nearly equal facility, suggesting that the metabolic specificity observed with the ketone precursor was not a function of the specificity of the transglucosylase or transacetylase but rather a result of compartmentation of each stereospecific dehydrogenase with the appropriate transferase. A UDP-glucose:monoterpenol glucosyltransferse, which utilized d-neomenthol or l-menthol as glucose acceptor, was demonstrated in the 105,000g supernatant of a peppermint leaf homogenate, and the enzyme was partially purified and characterized. Co-purification of the acceptor-mediated activities, and differential activation and inhibition studies, provided strong evidence that the same UDP-glucose-dependent enzyme could transfer glucose to either l-menthol or d-neomenthol. Determination of Km and V for the epimeric monoterpenols provided nearly identical values. The acetylcoenzyme A:monoterpenol acetyltransferase previously isolated from peppermint extracts (Croteau, Hooper 1978 Plant Physiol 61: 737-742) was re-examined using l-[3-3H]menthol and d-[3-3H]neomenthol as acetyl acceptors, and the Km and V for both epimers were, again, very similar. These results demonstrate that the specific in vivo

  10. Anaerobic Metabolism of Indoleacetate

    PubMed Central

    Ebenau-Jehle, Christa; Thomas, Markus; Scharf, Gernot; Kockelkorn, Daniel; Knapp, Bettina; Schühle, Karola; Heider, Johann

    2012-01-01

    The anaerobic metabolism of indoleacetate (indole-3-acetic acid [IAA]) in the denitrifying betaproteobacterium Azoarcus evansii was studied. The strain oxidized IAA completely and grew with a generation time of 10 h. Enzyme activities that transformed IAA were present in the soluble cell fraction of IAA-grown cells but were 10-fold downregulated in cells grown on 2-aminobenzoate or benzoate. The transformation of IAA did not require molecular oxygen but required electron acceptors like NAD+ or artificial dyes. The first products identified were the enol and keto forms of 2-oxo-IAA. Later, polar products were observed, which could not yet be identified. The first steps likely consist of the anaerobic hydroxylation of the N-heterocyclic pyrrole ring to the enol form of 2-oxo-IAA, which is catalyzed by a molybdenum cofactor-containing dehydrogenase. This step is probably followed by the hydrolytic ring opening of the keto form, which is catalyzed by a hydantoinase-like enzyme. A comparison of the proteome of IAA- and benzoate-grown cells identified IAA-induced proteins. Owing to the high similarity of A. evansii with strain EbN1, whose genome is known, we identified a cluster of 14 genes that code for IAA-induced proteins involved in the early steps of IAA metabolism. These genes include a molybdenum cofactor-dependent dehydrogenase of the xanthine oxidase/aldehyde dehydrogenase family, a hydantoinase, a coenzyme A (CoA) ligase, a CoA transferase, a coenzyme B12-dependent mutase, an acyl-CoA dehydrogenase, a fusion protein of an enoyl-CoA hydratase and a 3-hydroxyacyl-CoA dehydrogenase, a beta-ketothiolase, and a periplasmic substrate binding protein for ABC transport as well as a transcriptional regulator of the GntR family. Five predicted enzymes form or act on CoA thioesters, indicating that soon after the initial oxidation of IAA and possibly ring opening, CoA thioesters are formed, and the carbon skeleton is rearranged, followed by a CoA-dependent thiolytic

  11. Metabolism of Monoterpenes 1

    PubMed Central

    Croteau, Rodney; Sood, Virendar K.; Renstrøm, Britta; Bhushan, Ravi

    1984-01-01

    Previous studies have shown that the monoterpene ketone l-[G-3H] menthone is reduced to the epimeric alcohols l-menthol and d-neomenthol in leaves of flowering peppermint (Mentha piperita L.), and that a portion of the menthol is converted to menthyl acetate while the bulk of the neomenthol is transformed to neomenthyl-β-d-glucoside which is then transported to the rhizome (Croteau, Martinkus 1979 Plant Physiol 64: 169-175). Analysis of the disposition of l-[G-3H]menthone applied to midstem leaves of intact flowering plants allowed the kinetics of synthesis and transport of the monoterpenyl glucoside to be determined, and gave strong indication that the glucoside was subsequently metabolized in the rhizome. Studies with d-[G-3H]neomenthyl-β-d-glucoside as substrate, using excised rhizomes or rhizome segments, confirmed the hydrolysis of the glucoside as an early step in metabolism at this site, and revealed that the terpenoid moiety was further converted to a series of ether-soluble, methanol-soluble, and water-soluble products. Studies with d-[G-3H]neomenthol as the substrate, using excised rhizomes, showed the subsequent metabolic steps to involve oxidation of the alcohol back to menthone, followed by an unusual lactonization reaction in which oxygen is inserted between the carbonyl carbon and the carbon bearing the isopropyl group, to afford 3,4-menthone lactone. The conversion of menthone to the lactone, and of the lactone to more polar products, were confirmed in vivo using l-[G-3H]menthone and l-[G-3H]-3,4-menthone lactone as substrates. Additional oxidation products were formed in vivo via the desaturation of labeled neomenthol and/or menthone, but none of these transformations appeared to lead to ring opening of the p-menthane skeleton. Each step in the main reaction sequence, from hydrolysis of neomenthyl glucoside to lactonization of menthone, was demonstrated in cell-free extracts from the rhizomes of flowering mint plants. The lactonization step is of

  12. Hepatic iron metabolism.

    PubMed

    Anderson, Gregory J; Frazer, David M

    2005-11-01

    The liver performs three main functions in iron homeostasis. It is the major site of iron storage, it regulates iron traffic into and around the body through its production of the peptide hepcidin, and it is the site of synthesis of major proteins of iron metabolism such as transferrin and ceruloplasmin. Most of the iron that enters the liver is derived from plasma transferrin under normal circumstances, and transferrin receptors 1 and 2 play important roles in this process. In pathological situations, non-transferrin-bound iron, ferritin, and hemoglobin/haptoglobin and heme/hemopexin complexes assume greater importance in iron delivery to the organ. Iron is stored in the liver as ferritin and, with heavy iron loading, as hemosiderin. The liver can divest itself of iron through the plasma membrane iron exporter ferroportin 1, a process that also requires ceruloplasmin. Hepcidin can regulate this iron release through its interaction with ferroportin. PMID:16315136

  13. Regulation of Terpene Metabolism

    SciTech Connect

    Rodney Croteau

    2004-03-14

    OAK-B135 Research over the last four years has progressed fairly closely along the lines initially proposed, with progress-driven expansion of Objectives 1, 2 and 3. Recent advances have developed from three research thrusts: 1. Random sequencing of an enriched peppermint oil gland cDNA library has given access to a large number of potential pathway and regulatory genes for test of function; 2. The availability of new DNA probes and antibodies has permitted investigation of developmental regulation and organization of terpenoid metabolism; and 3. The development of a transformation system for peppermint by colleagues at Purdue University has allowed direct transgenic testing of gene function and added a biotechnological component to the project. The current status of each of the original research objectives is outlined below.

  14. Automated Microbial Metabolism Laboratory

    NASA Technical Reports Server (NTRS)

    1971-01-01

    The effect of several environmental parameters on previously developed life detection systems is explored. Initial attempts were made to conduct all the experiments in a moist mode (high soil volume to water volume ratio). However, only labeled release and measurement of ATP were found to be feasible under conditions of low moisture. Therefore, these two life detection experiments were used for most of the environmental effects studies. Three soils, Mojave (California desert), Wyaconda (Maryland, sandy loam) and Victoria Valley (Antarctic desert) were generally used throughout. The environmental conditions studied included: incubation temperature 3 C to 80 C, ultraviolet irradiation of soils, variations in soil/liquid ratio, specific atmospheric gases, various antimetabolites, specific substrates, and variation in pH. An experiment designed to monitor nitrogen metabolism was also investigated.

  15. Metabolism of proteinoid microspheres

    NASA Technical Reports Server (NTRS)

    Nakashima, T.; Fox, S. W. (Principal Investigator)

    1987-01-01

    The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolysis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

  16. Metabolism of proteinoid microspheres

    NASA Technical Reports Server (NTRS)

    Nakashima, T.; Fox, S. W. (Principal Investigator)

    1987-01-01

    The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolyis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

  17. Olfaction Under Metabolic Influences

    PubMed Central

    2012-01-01

    Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis. PMID:22832483

  18. Collagen Homeostasis and Metabolism.

    PubMed

    Magnusson, S Peter; Heinemeier, Katja M; Kjaer, Michael

    2016-01-01

    The musculoskeletal system and its collagen rich tissue is important for ensuring architecture of skeletal muscle, energy storage in tendon and ligaments, joint surface protection, and for ensuring the transfer of muscular forces into resulting limb movement. Structure of tendon is stable and the metabolic activity is low, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the tendon especially during youth and adolescence. Within short time, tendon will get stiffer with training and lack of mechanical tissue loading through inactivity or immobilization of the human body will conversely result in a dramatic loss in tendon stiffness and collagen synthesis. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. Adaptive responses may vary along the tendon, and differ between mid-substance and insertional areas of the tendon. PMID:27535245

  19. Adenosine and Bone Metabolism

    PubMed Central

    Mediero, Aránzazu; Cronstein, Bruce N.

    2013-01-01

    Bone is a dynamic organ that undergoes continuous remodeling whilst maintaining a balance between bone formation and resorption. Osteoblasts, which synthesize and mineralize new bone, and osteoclasts, the cells that resorb bone, act in concert to maintain bone homeostasis. In recent years, there has been increasing appreciation of purinergic regulation of bone metabolism. Adenosine, released locally, mediates its physiologic and pharmacologic actions via interactions with G-protein coupled receptors and recent work has indicated that these receptors are involved in the regulation of osteoclast differentiation and function, as well as osteoblast differentiation and bone formation. Moreover, adenosine receptors also regulate chondrocyte and cartilage homeostasis. These recent findings underscore the potential therapeutic importance of adenosine receptors in regulating bone physiology and pathology. PMID:23499155

  20. Metabolism during hypodynamia

    NASA Technical Reports Server (NTRS)

    Federov, I. V.

    1980-01-01

    Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

  1. Metabolism of endocannabinoids.

    PubMed

    Biernacki, Michał; Skrzydlewska, Elżbieta

    2016-01-01

    Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown. Endocannabinoids are synthesized from phospholipids (mainly phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol) located in the cell membrane. As a result of arachidonic acid transfer from phosphatidylcholine to phosphatidylethanolamine, N-arachidonoyl phosphatidylethanolamine is formed, which is hydrolyzed to AEA by phospholipase D, C and A2. However, 2-AG is formed during the hydrolysis of phosphatidylinositol catalyzed mainly by DAGL. The primary role of endocannabinoids is the activation of cannabinoid receptors. Both AEA and 2-AG are primarily agonists of the CB1 receptor and to a lower degree CB2 and TRPV1r eceptors, but 2-AG has stronger affinity for these receptors. Through activation of receptors, endocannabinoids affect cellular metabolism and participate in the metabolic processes by receptor-independent pathways. Endocannabinoids which are not bound to the receptors are degraded. The main enzymes responsible for the hydrolysis of AEA and 2-AG are FAAH and MAGL, respectively. Apart from hydrolytic degradation, endocannabinoids may also be oxidized by cyclooxygenase-2, lipoxygenases, and cytochrome P450. It has been shown that the metabolites of both endocannabinoids also have biological significance. PMID:27516570

  2. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  3. Metabolism of Monoterpenes 1

    PubMed Central

    Croteau, Rodney; El-Bialy, Hamdy; Dehal, Shangara S.

    1987-01-01

    The bicyclic monoterpene ketone (+)-camphor undergoes lactonization to 1,2-campholide in mature sage (Salvia officinalis L.) leaves followed by conversion to the β-d-glucoside-6-O-glucose ester of the corresponding hydroxy acid (1-carboxymethyl-3-hydroxy-2,2,3-trimethyl cyclopentane). Analysis of the disposition of (+)-[G-3H]camphor applied to midstem leaves of intact flowering plants allowed the kinetics of synthesis of the bis-glucose derivative and its transport from leaf to root to be determined, and gave strong indication that the transport derivative was subsequently metabolized in the root. Root extracts were shown to possess β-glucosidase and acyl glucose esterase activities, and studies with (+)-1,2[U-14C]campholide as substrate, using excised root segments, revealed that the terpenoid was converted to lipid materials. Localization studies confirmed the radiolabeled lipids to reside in the membranous fractions of root extracts, and analysis of this material indicated the presence of labeled phytosterols and labeled fatty acids (C14 to C20) of acyl lipids. Although it was not possible to detail the metabolic steps between 1,2-campholide and the acyl lipids and phytosterols derived therefrom because of the lack of readily detectable intermediates, it seemed likely that the monoterpene lactone was degraded to acetyl CoA which was reincorporated into root membrane components via standard acyl lipid and isoprenoid biosynthetic pathways. Monoterpene catabolism thus appears to represent a salvage mechanism for recycling mobile carbon from senescing oil glands on the leaves to the roots. PMID:16665495

  4. Lysophosphatidylinositol Signalling and Metabolic Diseases.

    PubMed

    Arifin, Syamsul A; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  5. Cancer Metabolism and Drug Resistance

    PubMed Central

    Rahman, Mahbuba; Hasan, Mohammad Rubayet

    2015-01-01

    Metabolic alterations, driven by genetic and epigenetic factors, have long been known to be associated with the etiology of cancer. Furthermore, accumulating evidence suggest that cancer metabolism is intimately linked to drug resistance, which is currently one of the most important challenges in cancer treatment. Altered metabolic pathways help cancer cells to proliferate at a rate higher than normal, adapt to nutrient limited conditions, and develop drug resistance phenotypes. Application of systems biology, boosted by recent advancement of novel high-throughput technologies to obtain cancer-associated, transcriptomic, proteomic and metabolomic data, is expected to make a significant contribution to our understanding of metabolic properties related to malignancy. Indeed, despite being at a very early stage, quantitative data obtained from the omics platforms and through applications of 13C metabolic flux analysis (MFA) in in vitro studies, researchers have already began to gain insight into the complex metabolic mechanisms of cancer, paving the way for selection of molecular targets for therapeutic interventions. In this review, we discuss some of the major findings associated with the metabolic pathways in cancer cells and also discuss new evidences and achievements on specific metabolic enzyme targets and target-directed small molecules that can potentially be used as anti-cancer drugs. PMID:26437434

  6. Clinical Disorders of Phosphorus Metabolism

    PubMed Central

    Yu, George C.; Lee, David B. N.

    1987-01-01

    Deranged phosphorus metabolism is commonly encountered in clinical medicine. Disturbances in phosphate intake, excretion and transcellular shift account for the abnormal serum levels. As a result of the essential role played by phosphate in intracellular metabolism, the clinical manifestations of hypophosphatemia and hyperphosphatemia are extensive. An understanding of the pathophysiology of various phosphate disorders is helpful in guiding therapeutic decisions. Images PMID:3321712

  7. Estrogen Signaling in Metabolic Inflammation

    PubMed Central

    Monteiro, Rosário; Teixeira, Diana; Calhau, Conceição

    2014-01-01

    There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions. PMID:25400333

  8. Selected Metabolic Responses to Skateboarding

    ERIC Educational Resources Information Center

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  9. Lysophosphatidylinositol Signalling and Metabolic Diseases

    PubMed Central

    Arifin, Syamsul A.; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  10. Obesity, metabolic syndrome and adipocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and metabolic syndrome are examples whereby excess energy consumption and energy flux disruptions are causative agents of increased fatness. Because other, as yet elucidated, cellular factors may be involved and because potential treatments of these metabolic problems involve systemic agents...

  11. Mitochondrial sirtuins and metabolic homeostasis

    PubMed Central

    Pirinen, Eija; Sasso, Giuseppe Lo; Auwerx, Johan

    2013-01-01

    The maintenance of metabolic homeostasis requires the well-orchestrated network of several pathways of glucose, lipid and amino acid metabolism. Mitochondria integrate these pathways and serve not only as the prime site of cellular energy harvesting but also as the producer of many key metabolic intermediates. The sirtuins are a family of NAD+-dependent enzymes, which have a crucial role in the cellular adaptation to metabolic stress. The mitochondrial sirtuins SIRT3, SIRT4 and SIRT5 together with the nuclear SIRT1 regulate several aspects of mitochondrial physiology by controlling posttranslational modifications of mitochondrial protein and transcription of mitochondrial genes. Here we discuss current knowledge how mitochondrial sirtuins and SIRT1 govern mitochondrial processes involved in different metabolic pathways. PMID:23168278

  12. Metabolic Mechanisms of Epigenetic Regulation

    PubMed Central

    Meier, Jordan L.

    2014-01-01

    Chromatin modifications have been well-established to play a critical role in the regulation of genome function. Many of these modifications are introduced and removed by enzymes that utilize cofactors derived from primary metabolism. Recently, it has been shown that endogenous cofactors and metabolites can regulate the activity of chromatin-modifying enzymes, providing a direct link between the metabolic state of the cell and epigenetics. Here we review metabolic mechanisms of epigenetic regulation with an emphasis on their role in cancer. Focusing on three core mechanisms, we detail and draw parallels between metabolic and chemical strategies to modulate epigenetic signaling, and highlight opportunities for chemical biologists to help shape our knowledge of this emerging phenomenon. Continuing to integrate our understanding of metabolic and genomic regulatory mechanisms may help elucidate the role of nutrition in diseases such as cancer, while also providing a basis for new approaches to modulate epigenetic signaling for therapeutic benefit. PMID:24228614

  13. Fetal Programming and Metabolic Syndrome

    PubMed Central

    Rinaudo, Paolo; Wang, Erica

    2014-01-01

    Metabolic syndrome is reaching epidemic proportions, particularly in developing countries. In this review, we explore the concept—based on the developmental-origin-of-health-and-disease hypothesis—that reprogramming during critical times of fetal life can lead to metabolic syndrome in adulthood. Specifically, we summarize the epidemiological evidence linking prenatal stress, manifested by low birth weight, to metabolic syndrome and its individual components. We also review animal studies that suggest potential mechanisms for the long-term effects of fetal reprogramming, including the cellular response to stress and both organ- and hormone-specific alterations induced by stress. Although metabolic syndrome in adulthood is undoubtedly caused by multiple factors, including modifiable behavior, fetal life may provide a critical window in which individuals are predisposed to metabolic syndrome later in life. PMID:21910625

  14. [Metabolic syndrome--psychosomatic associations].

    PubMed

    Kolesnikov, D B; Rapoport, S I

    2008-01-01

    According to epidemiological investigations data, 10 to 35% of all population suffers from metabolic syndrome. However, until now, in spite of researches, metabolic syndrome remains little-studied complex problem. The aim of the review is summarized analysis of the researches results, going out the limits of internal diseases clinics and reflecting more complicated, psychosomatic mechanisms of the syndrome development. The data of literature indicate the row of patterns in development of psyche and metabolic processes disturbances. Analysis of various directions in study of metabolic syndrome with concomitant mental disturbances is represented in the article. The authors propose to perform further investigation subject to "multisectorality" of the disease, marking out prevailing mechanisms of development of metabolic syndrome subject to somatic and mental factors. PMID:18368784

  15. Ethnic Considerations for Metabolic Surgery.

    PubMed

    Morton, John Magaña

    2016-06-01

    Obesity and diabetes represent twin health concerns in the developed world. Metabolic surgery has emerged as an established and enduring treatment for both obesity and diabetes. As the burden of obesity and diabetes varies upon the basis of ethnicity, it is also apparent that there may be differences for indications and outcomes for different ethnic groups after metabolic surgery. Whereas there appears to be evidence for variation in weight loss and complications for different ethnic groups, comorbidity remission particularly for diabetes appears to be free of ethnic disparity after metabolic surgery. The impacts of access, biology, culture, genetics, procedure, and socioeconomic status upon metabolic surgery outcomes are examined. Further refinement of the influence of ethnicity upon metabolic surgery outcomes is likely imminent. PMID:27222553

  16. Metabolic exchanges within tumor microenvironment.

    PubMed

    Chiarugi, Paola; Cirri, Paolo

    2016-09-28

    Tumor progression toward malignancy often requires a metabolic rewiring of cancer cells to meet changes in metabolic demand to forefront nutrient and oxygen withdrawal, together with strong anabolic requests to match high proliferation rate. Tumor microenvironment highly contributes to metabolic rewiring of cancer cells, fostering complete nutrient exploitation, favoring OXPHOS of lipids and glutamine at the expense of glycolysis and enhancing exchanges via extracellular microvesicles or exosomes of proteins, lipids and small RNAs among tumor and stromal cells. Noteworthy, the same molecular drivers of metabolic reprogramming within tumor and stroma are also able to elicit motility, survival and self-renewal on cancer cells, thereby sustaining successful escaping strategies to circumvent the hostile hypoxic, acidic and inflammatory environment. This review highlights the emerging role of nutrients and vesicle-mediated exchanges among tumor and stromal cells, defining their molecular pathways and offering new perspectives to develop treatments targeting this complex metabolic rewiring. PMID:26546872

  17. [Hypovitaminosis D and metabolic syndrome].

    PubMed

    Miñambres, Inka; de Leiva, Alberto; Pérez, Antonio

    2014-12-23

    Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies. Overall, because of the high prevalence and the epidemiological association between both diseases, hypovitaminosis D could be considered a component of the metabolic syndrome. PMID:24529881

  18. Fructose metabolism in the cerebellum.

    PubMed

    Funari, Vincent A; Crandall, James E; Tolan, Dean R

    2007-01-01

    Under normal physiological conditions, the brain utilizes only a small number of carbon sources for energy. Recently, there is growing molecular and biochemical evidence that other carbon sources, including fructose, may play a role in neuro-energetics. Fructose is the number one commercial sweetener in Western civilization with large amounts of fructose being toxic, yet fructose metabolism remains relatively poorly characterized. Fructose is purportedly metabolized via either of two pathways, the fructose-1-phosphate pathway and/or the fructose-6-phosphate pathway. Many early metabolic studies could not clearly discriminate which of these two pathways predominates, nor could they distinguish which cell types in various tissues are capable of fructose metabolism. In addition, the lack of good physiological models, the diet-induced changes in gene expression in many tissues, the involvement of multiple genes in multiple pathways involved in fructose metabolism, and the lack of characterization of some genes involved in fructose metabolism have complicated our understanding of the physiological role of fructose in neuro-energetics. A recent neuro-metabolism study of the cerebellum demonstrated fructose metabolism and co-expression of the genes specific for the fructose 1-phosphate pathway, GLUT5 (glut5) and ketohexokinase (khk), in Purkinje cells suggesting this as an active pathway in specific neurons? Meanwhile, concern over the rapid increase in dietary fructose, particularly among children, has increased awareness about how fructose is metabolized in vivo and what effects a high fructose diet might have. In this regard, establishment of cellular and molecular studies and physiological characterization of the important and/or deleterious roles fructose plays in the brain is critical. This review will discuss the status of fructose metabolism in the brain with special reference to the cerebellum and the physiological roles of the different pathways. PMID:17510913

  19. Metabolic profiling reveals key metabolic features of renal cell carcinoma

    PubMed Central

    Catchpole, Gareth; Platzer, Alexander; Weikert, Cornelia; Kempkensteffen, Carsten; Johannsen, Manfred; Krause, Hans; Jung, Klaus; Miller, Kurt; Willmitzer, Lothar; Selbig, Joachim; Weikert, Steffen

    2011-01-01

    Abstract Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC. PMID:19845817

  20. Marrow fat metabolism is linked to the systemic energy metabolism

    PubMed Central

    Lecka-Czernik, Beata

    2011-01-01

    Recent advances in understanding the role of bone in the systemic regulation of energy metabolism indicate that bone marrow cells, adipocytes and osteoblasts, are involved in this process. Marrow adipocytes store significant quantities of fat and produce adipokines, leptin and adiponectin, which are known for their role in the regulation of energy metabolism, whereas osteoblasts produce osteocalcin, a bone-specific hormone that has a potential to regulate insulin production in the pancreas and adiponectin production in fat tissue. Both osteoblasts and marrow adipocytes express insulin receptor and respond to insulin-sensitizing anti-diabetic TZDs in a manner, which tightly links bone with the energy metabolism system. Metabolic profile of marrow fat resembles that of both, white and brown fat, which is reflected by its plasticity in acquiring different functions including maintenance of bone micro-environment. Marrow fat responds to physiologic and pathologic changes in energy metabolism status by changing volume and metabolic activity. This review summarizes available information on the metabolic function of marrow fat and provides hypothesis that this fat depot may acquire multiple roles depending on the local and perhaps systemic demands. These functions may include a role in bone energy maintenance and endocrine activities to serve osteogenesis during bone remodeling and bone healing. PMID:21757043

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

    PubMed

    Zeisel, Steven H

    2013-03-01

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

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

    PubMed Central

    Zeisel, Steven H.

    2013-01-01

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

  3. Treatment of Amino Acid Metabolism Disorders

    MedlinePlus

    ... Treatment of amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please ... this page It's been added to your dashboard . Amino acid metabolism disorders are rare health conditions that affect ...

  4. Microbial metabolism of tholin

    NASA Astrophysics Data System (ADS)

    Stoker, C. R.; Boston, P. J.; Mancinelli, R. L.; Segal, W.; Khare, B. N.; Sagan, C.

    1990-05-01

    In this paper, we show that a wide variety of common soil bacteria are able to obtain their carbon and energy needs from tholin (a class of complex organic heteropolymers thought to be widely distributed through the solar system; in this case tholin was produced by passage of electrical discharge through a mixture of methane, ammonia, and water vapor). We have isolated aerobic, anaerobic, and facultatively anaerobic bacteria which are able to use tholin as a sole carbon source. Organisms which metabolize tholin represent a variety of bacterial genera including Clostridium, Pseudomonas, Bacillus, Acinetobacter, Paracoccus, Alcaligenes, Micrococcus, Cornebacterium, Aerobacter, Arthrobacter, Flavobacterium,and Actinomyces. Aerobic tholin-using bacteria were firrst isolated from soils containing unusual or sparse carbon sources. Some of these organisms were found to be facultatively anaerobic. Strictly anaerobic tholin-using bacteria were isolated from both carbon-rich and carbon-poor anaerobic lake muds. In addition, both aerobic and anaerobic tholin-using bacteria were isolated from common soil collected outside the laboratory building. Some, but not all, of the strains that were able to obtain carbon from tholin were also able to obtain their nitrogen requirements from tholin. Bacteria isolated from common soils were tested for their ability to obtain carbon from the water-soluble fraction, the ethanol-soluble fraction, and the water/ethanol-insoluble fraction of the tholin. Of the 3.5 × 10 7 bacteria isolated per gram of common soils, 1.7 0.5, and 0.2%, respectively, were able to obtaib their carbon requirements from the water-soluble fraction, the ethanol-soluble fraction and the water/ethanol-insoluble fraction of the tholin. The palatability of tholins to modern microbes may have implications for the early evolution of microbial life on Earth. Tholins may have formed the base of the food chain for an early heterotrophic biosphere before the evolution of

  5. Calcium metabolism in microgravity.

    PubMed

    Heer, M; Kamps, N; Biener, C; Korr, C; Boerger, A; Zittermann, A; Stehle, P; Drummer, C

    1999-09-01

    Unloading of weight bearing bones as induced by microgravity or immobilization has significant impacts on the calcium and bone metabolism and is the most likely cause for space osteoporosis. During a 4.5 to 6 month stay in space most of the astronauts develop a reduction in bone mineral density in spine, femoral neck, trochanter, and pelvis of 1%-1.6% measured by Dual Energy X-ray Absorption (DEXA). Dependent on the mission length and the individual turnover rates of the astronauts it can even reach individual losses of up to 14% in the femoral neck. Osteoporosis itself is defined as the deterioration of bone tissue leading to enhanced bone fragility and to a consequent increase in fracture risk. Thinking of long-term missions to Mars or interplanetary missions for years, space osteoporosis is one of the major concerns for manned spaceflight. However, decrease in bone density can be initiated differently. It either can be caused by increases in bone formation and bone resorption resulting in a net bone loss, as obtained in fast looser postmenopausal osteoporosis. On the other hand decrease in bone formation and increase in bone resorption also leads to bone losses as obtained in slow looser postmenopausal osteoporosis or in Anorexia Nervosa patients. Biomarkers of bone turnover measured during several missions indicated that the pattern of space osteoporosis is very similar to the pattern of Anorexia Nervosa patients or slow looser postmenopausal osteoporosis. However, beside unloading, other risk factors for space osteoporosis exist such as stress, nutrition, fluid shifts, dehydration and bone perfusion. Especially nutritional factors may contribute considerably to the development of osteoporosis. From earthbound studies it is known that calcium supplementation in women and men can prevent bone loss of 1% bone per year. Based on these results we studied the calcium intake during several European missions and performed an experiment during the German MIR 97 mission

  6. Alcohol and porphyrin metabolism.

    PubMed

    Doss, M O; Kühnel, A; Gross, U

    2000-01-01

    Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem

  7. Cancer Metabolism: A Modeling Perspective

    PubMed Central

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells. Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome-scale metabolic modeling approaches in perceiving a system-level perspective of cancer metabolism and in detecting novel selective drug targets. PMID:26733270

  8. Metabolic control of cell death

    PubMed Central

    Green, Douglas R.; Galluzzi, Lorenzo; Kroemer, Guido

    2014-01-01

    Summary Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries including oxidative phosphorylation and transport of metabolites across membranes may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of “metabolic checkpoints” that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss. PMID:25237106

  9. Metabolic reprogramming during neuronal differentiation.

    PubMed

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  10. Glucose metabolism and cardiac hypertrophy

    PubMed Central

    Kolwicz, Stephen C.; Tian, Rong

    2011-01-01

    The most notable change in the metabolic profile of hypertrophied hearts is an increased reliance on glucose with an overall reduced oxidative metabolism, i.e. a reappearance of the foetal metabolic pattern. In animal models, this change is attributed to the down-regulation of the transcriptional cascades promoting gene expression for fatty acid oxidation and mitochondrial oxidative phosphorylation in adult hearts. Impaired myocardial energetics in cardiac hypertrophy also triggers AMP-activated protein kinase (AMPK), leading to increased glucose uptake and glycolysis. Aside from increased reliance on glucose as an energy source, changes in other glucose metabolism pathways, e.g. the pentose phosphate pathway, the glucosamine biosynthesis pathway, and anaplerosis, are also noted in the hypertrophied hearts. Studies using transgenic mouse models and pharmacological compounds to mimic or counter the switch of substrate preference in cardiac hypertrophy have demonstrated that increased glucose metabolism in adult heart is not harmful and can be beneficial when it provides sufficient fuel for oxidative metabolism. However, improvement in the oxidative capacity and efficiency rather than the selection of the substrate is likely the ultimate goal for metabolic therapies. PMID:21502371

  11. Lipid metabolism in prostate cancer

    PubMed Central

    Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

    2014-01-01

    The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

  12. [EEG manifestations in metabolic encephalopathy].

    PubMed

    Lin, Chou-Ching K

    2005-09-01

    Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized. PMID:16252619

  13. Mitochondrial Morphology in Metabolic Diseases

    PubMed Central

    Galloway, Chad A.

    2013-01-01

    Abstract Significance: Mitochondria are the cellular energy-producing organelles and are at the crossroad of determining cell life and death. As such, the function of mitochondria has been intensely studied in metabolic disorders, including diabetes and associated maladies commonly grouped under all-inclusive pathological condition of metabolic syndrome. More recently, the altered metabolic profiles and function of mitochondria in these ailments have been correlated with their aberrant morphologies. This review describes an overview of mitochondrial fission and fusion machineries, and discusses implications of mitochondrial morphology and function in these metabolic maladies. Recent Advances: Mitochondria undergo frequent morphological changes, altering the mitochondrial network organization in response to environmental cues, termed mitochondrial dynamics. Mitochondrial fission and fusion mediate morphological plasticity of mitochondria and are controlled by membrane-remodeling mechanochemical enzymes and accessory proteins. Growing evidence suggests that mitochondrial dynamics play an important role in diabetes establishment and progression as well as associated ailments, including, but not limited to, metabolism–secretion coupling in the pancreas, nonalcoholic fatty liver disease progression, and diabetic cardiomyopathy. Critical Issues: While mitochondrial dynamics are intimately associated with mitochondrial bioenergetics, their cause-and-effect correlation remains undefined in metabolic diseases. Future Directions: The involvement of mitochondrial dynamics in metabolic diseases is in its relatively early stages. Elucidating the role of mitochondrial dynamics in pathological metabolic conditions will aid in defining the intricate form–function correlation of mitochondria in metabolic pathologies and should provide not only important clues to metabolic disease progression, but also new therapeutic targets. Antioxid. Redox Signal. 19, 415–430. PMID:22793999

  14. Energy Metabolism in the Liver

    PubMed Central

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  15. Equine metabolic syndrome

    PubMed Central

    Morgan, R.; Keen, J.; McGowan, C.

    2015-01-01

    Laminitis is one of the most common and frustrating clinical presentations in equine practice. While the principles of treatment for laminitis have not changed for several decades, there have been some important paradigm shifts in our understanding of laminitis. Most importantly, it is essential to consider laminitis as a clinical sign of disease and not as a disease in its own right. Once this shift in thinking has occurred, it is logical to then question what disease caused the laminitis. More than 90 per cent of horses presented with laminitis as their primary clinical sign will have developed it as a consequence of endocrine disease; most commonly equine metabolic syndrome (EMS). Given the fact that many horses will have painful protracted and/or chronic recurrent disease, a good understanding of the predisposing factors and how to diagnose and manage them is crucial. Current evidence suggests that early diagnosis and effective management of EMS should be a key aim for practising veterinary surgeons to prevent the devastating consequences of laminitis. This review will focus on EMS, its diagnosis and management. PMID:26273009

  16. Regulation of sphingomyelin metabolism.

    PubMed

    Bienias, Kamil; Fiedorowicz, Anna; Sadowska, Anna; Prokopiuk, Sławomir; Car, Halina

    2016-06-01

    Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD). PMID:26940196

  17. Heme Metabolism and Erythropoiesis

    PubMed Central

    Chung, Jacky; Chen, Caiyong; Paw, Barry H.

    2014-01-01

    Purpose of review Heme biosynthesis requires a series of enzymatic reactions that take place in the cytosol and the mitochondria as well as the proper inter- and intracellular trafficking of iron. Heme can also be acquired by intestinal absorption and intercellular transport. The purpose of this review is to highlight recent work on heme and iron transport with an emphasis on their relevance in erythropoiesis. Recent findings While the enzymes responsible for heme biosynthesis have been identified, transport mechanisms for iron, heme, or heme synthesis intermediates are only emerging. Recent studies have shed light into how these molecules are transported among various cellular compartments, as well as tissues. Much of this progress can be attributed to the use of model organisms such as S. cerevisiae, C. elegans, D. rerio, and M. musculus. Genetic studies in these models have led to the identification of several new genes involved in heme metabolism. Although our understanding has greatly improved, it is highly likely that other regulators exist and additional work is required to characterize the pathways by which heme and iron are transported within the erythron. Summary The identification of heme and iron transport mechanisms will improve our understanding of blood development and provide new insight into human blood disorders. PMID:22406824

  18. Nitrogen metabolism in haloarchaea

    PubMed Central

    Bonete, María José; Martínez-Espinosa, Rosa María; Pire, Carmen; Zafrilla, Basilio; Richardson, David J

    2008-01-01

    The nitrogen cycle (N-cycle), principally supported by prokaryotes, involves different redox reactions mainly focused on assimilatory purposes or respiratory processes for energy conservation. As the N-cycle has important environmental implications, this biogeochemical cycle has become a major research topic during the last few years. However, although N-cycle metabolic pathways have been studied extensively in Bacteria or Eukarya, relatively little is known in the Archaea. Halophilic Archaea are the predominant microorganisms in hot and hypersaline environments such as salted lakes, hot springs or salted ponds. Consequently, the denitrifying haloarchaea that sustain the nitrogen cycle under these conditions have emerged as an important target for research aimed at understanding microbial life in these extreme environments. The haloarchaeon Haloferax mediterranei was isolated 20 years ago from Santa Pola salted ponds (Alicante, Spain). It was described as a denitrifier and it is also able to grow using NO3-, NO2- or NH4+ as inorganic nitrogen sources. This review summarizes the advances that have been made in understanding the N-cycle in halophilic archaea using Hfx mediterranei as a haloarchaeal model. The results obtained show that this microorganism could be very attractive for bioremediation applications in those areas where high salt, nitrate and nitrite concentrations are found in ground waters and soils. PMID:18593475

  19. [Regulation of terpene metabolism

    SciTech Connect

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  20. Metabolism of lorazepam.

    PubMed

    Elliott, H W

    1976-10-01

    The metabolism of lorazepam by man and four other species is reviewed. Lorazepam and its metabolites in blood, urine and faeces were identified by thin-layer and gas chromatography and by mass spectrometry. The principal metabolite in man, dog, pig and cat is the glucuronide, but the rat produces other metabolites after small doses of lorazepam, and significant amounts of the glucuronide only after high doses. Since all metabolites, except the glucuronide, occur in small quantities only in man, most studies in man have been confined to an estimation of gree and conjugated lorazepam. Blood concentrations of unconjugated lorazepam peak at 1-4 h, significant concentrations persisting for 24 h and decreasing slowly over the next 24 h. About 95% of a dose of lorazepam was accounted for in urine and faeces over a period of 5 days; 74.5% was excreted in the urine as lorazepam glucuronide and 13.5% as minor metabolites. The excretory half-life was 12 h. The blood concentrations and excretion rates are compatible with the clinical effects of lorazepam. PMID:10938

  1. Automated Microbial Metabolism Laboratory

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The Automated Microbial Metabolism Laboratory (AMML) 1971-1972 program involved the investigation of three separate life detection schemes. The first was a continued further development of the labeled release experiment. The possibility of chamber reuse without inbetween sterilization, to provide comparative biochemical information was tested. Findings show that individual substrates or concentrations of antimetabolites may be sequentially added to a single test chamber. The second detection system which was investigated for possible inclusion in the AMML package of assays, was nitrogen fixation as detected by acetylene reduction. Thirdly, a series of preliminary steps were taken to investigate the feasibility of detecting biopolymers in soil. A strategy for the safe return to Earth of a Mars sample prior to manned landings on Mars is outlined. The program assumes that the probability of indigenous life on Mars is unity and then broadly presents the procedures for acquisition and analysis of the Mars sample in a manner to satisfy the scientific community and the public that adequate safeguards are being taken.

  2. Acyl-lipid metabolism.

    PubMed

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X; Arondel, Vincent; Bates, Philip D; Baud, Sébastien; Bird, David; Debono, Allan; Durrett, Timothy P; Franke, Rochus B; Graham, Ian A; Katayama, Kenta; Kelly, Amélie A; Larson, Tony; Markham, Jonathan E; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  3. Acyl-lipid metabolism.

    PubMed

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X; Arondel, Vincent; Bates, Philip D; Baud, Sébastien; Bird, David; Debono, Allan; Durrett, Timothy P; Franke, Rochus B; Graham, Ian A; Katayama, Kenta; Kelly, Amélie A; Larson, Tony; Markham, Jonathan E; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2010-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:22303259

  4. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2010-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:22303259

  5. Acyl-Lipid Metabolism

    PubMed Central

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  6. Folate metabolism in malaria

    PubMed Central

    Ferone, Robert

    1977-01-01

    It is known that malaria parasites are inhibited by sulfonamides and antifolate compounds, require 4-aminobenzoic acid for growth, and respond only partly to intact folic and folinic acids. Biochemical data obtained during the last decade on the synthesis of nucleic acid precursors and on folate enzymes in malaria support the hypothesis that malaria parasites are similar to microorganisms that synthesize folate cofactors de novo. Sulfa drugs inhibit plasmodial dihydropteroate synthase (EC 2.5.1.15). Pyrimethamine and many other antifolate compounds bind to tetrahydrofolate dehydrogenase (EC 1.5.1.3) of the parasite more tightly than to the host enzyme. However, the metabolic consequences of the depletion of folate cofactors as a result of drug inhibition are not yet known. Other areas to be studied are the origin of the pteridine moiety of folates, the addition of glutamate(s) in folate cofactor biosynthesis, the means by which intact, exogenous folates affect malarial growth, and demonstration of the enzymes and reactions involving N5-methyl tetrahydrofolate. PMID:338184

  7. Acetoin metabolism in bacteria.

    PubMed

    Xiao, Zijun; Xu, Ping

    2007-01-01

    Acetoin is an important physiological metabolite excreted by many microorganisms. The excretion of acetoin, which can be diagnosed by the Voges Proskauer test and serves as a microbial classification marker, has its vital physiological meanings to these microbes mainly including avoiding acification, participating in the regulation of NAD/NADH ratio, and storaging carbon. The well-known anabolism of acetoin involves alpha-acetolactat synthase and alpha-acetolactate decarboxylase; yet its catabolism still contains some differing views, although much attention has been focused on it and great advances have been achieved. Current findings in catabolite control protein A (CcpA) mediated carbon catabolite repression may provide a fuller understanding of the control mechanism in bacteria. In this review, we first examine the acetoin synthesis pathways and its physiological meanings and relevancies; then we discuss the relationship between the two conflicting acetoin cleavage pathways, the enzymes of the acetoin dehydrogenase enzyme system, major genes involved in acetoin degradation, and the CcpA mediated acetoin catabolite repression pathway; in the end we discuss the genetic engineering progresses concerning applications. To date, this is the first integrated review on acetoin metabolism in bacteria, especially with regard to catabolic aspects. The apperception of the generation and dissimilation of acetoin in bacteria will help provide a better understanding of microbial strategies in the struggle for resources, which will consequently better serve the utilization of these microbes. PMID:17558661

  8. Metabolic inflexibility: when mitochondrial indecision leads to metabolic gridlock.

    PubMed

    Muoio, Deborah M

    2014-12-01

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility. PMID:25480291

  9. Metabolic Inflexibility: When Mitochondrial Indecision Leads to Metabolic Gridlock

    PubMed Central

    Muoio, Deborah M.

    2016-01-01

    Normal energy metabolism is characterized by periodic shifts in glucose and fat oxidation, as the mitochondrial machinery responsible for carbon combustion switches freely between alternative fuels according to physiological and nutritional circumstances. These transitions in fuel choice are orchestrated by an intricate network of metabolic and cell signaling events that enable exquisite crosstalk and cooperation between competing substrates to maintain energy and glucose homeostasis. By contrast, obesity-related cardiometabolic diseases are increasingly recognized as disorders of metabolic inflexibility, in which nutrient overload and heightened substrate competition result in mitochondrial indecision, impaired fuel switching, and energy dysregulation. This Perspective offers a speculative view on the molecular origins and pathophysiological consequences of metabolic inflexibility. PMID:25480291

  10. Metabolic effects of artificial environments

    NASA Technical Reports Server (NTRS)

    Jordan, J. P.

    1973-01-01

    Effects of diluent gases on the metabolism of animals breathing nitrogen-oxygen, argon-oxygen, and helium-oxygen mixtures were studied. Results show that helium actually affected the mean free path of oxygen across the alveoli and increased metabolic rate. It is speculated that it might be necessary to keep an astronaut in a depressed metabolic state during prolonged space flight by using an argon-oxygen or a xenon-nitrogen mixture for breathing. Replacement of the depressant gases during periods requiring critical spacecraft maneuvers by neon-oxygen mixtures would insure maximal performance.

  11. Energy metabolism in nuclear reprogramming.

    PubMed

    Folmes, Clifford D L; Nelson, Timothy J; Terzic, Andre

    2011-12-01

    Nuclear reprogramming with stemness factors enables resetting of somatic differentiated tissue back to the pluripotent ground state. Recent evidence implicates mitochondrial restructuring and bioenergetic plasticity as key components underlying execution of orchestrated dedifferentiation and derivation of induced pluripotent stem cells. Aerobic to anaerobic transition of somatic oxidative energy metabolism into a glycolytic metabotype promotes proficient reprogramming, establishing a novel regulator of acquired stemness. Metabolomic profiling has further identified specific metabolic remodeling traits defining lineage redifferentiation of pluripotent cells. Therefore, mitochondrial biogenesis and energy metabolism comprise a vital axis for biomarker discovery, intimately reflecting the molecular dynamics fundamental for the resetting and redirection of cell fate. PMID:22103608

  12. Energy metabolism in nuclear reprogramming

    PubMed Central

    Folmes, Clifford DL; Nelson, Timothy J; Terzic, Andre

    2012-01-01

    Nuclear reprogramming with stemness factors enables resetting of somatic differentiated tissue back to the pluripotent ground state. Recent evidence implicates mitochondrial restructuring and bioenergetic plasticity as key components underlying execution of orchestrated dedifferentiation and derivation of induced pluripotent stem cells. Aerobic to anaerobic transition of somatic oxidative energy metabolism into a glycolytic metabotype promotes proficient reprogramming, establishing a novel regulator of acquired stemness. Metabolomic profiling has further identified specific metabolic remodeling traits defining lineage redifferentiation of pluripotent cells. Therefore, mitochondrial biogenesis and energy metabolism comprise a vital axis for biomarker discovery, intimately reflecting the molecular dynamics fundamental for the resetting and redirection of cell fate. PMID:22103608

  13. Mitofusins, from Mitochondria to Metabolism.

    PubMed

    Schrepfer, Emilie; Scorrano, Luca

    2016-03-01

    Mitochondrial architecture is involved in several functions crucial for cell viability, proliferation, senescence, and signaling. In particular, mitochondrial dynamics, through the balance between fusion and fission events, represents a central mechanism for bioenergetic adaptation to metabolic needs of the cell. As key regulators of mitochondrial dynamics, the fusogenic mitofusins have recently been linked to mitochondrial biogenesis and respiratory functions, impacting on cell fate and organism homeostasis. Here we review the implication of mitofusins in the regulation of mitochondrial metabolism, and their consequence on energy homeostasis at the cellular and physiological level, highlighting their crucial role in metabolic disorders, cancer, and aging. PMID:26942673

  14. Intermediary metabolism of Trypanosoma cruzi.

    PubMed

    Urbina, J A

    1994-03-01

    In this article, Julio Urbino discusses the characteristics o f the intermediary metabolism of Trypanosoma cruzi (the causative agent of Chagas disease), which are responsible for the unusual capacity of this parasite to use carbohydrates or amino acids as carbon and energy sources without drastic changes in its catabolic enzyme levels(1-3). Many, but not all, o f the metabolic capabilities of this organism are shared with Leishmania and the procyclic form o f the African trypanosomes, and the reviewer presents a metabolic model which is also consistent with the information available on these other parasites(2,4). PMID:15275492

  15. [Metabolic syndrome and diabetes mellitus].

    PubMed

    2013-09-01

    Metabolic syndrome is based on visceral fat accumulation and brings about various metabolic abnormality such as hypertention, dyslipidemia, and glucose intolerance with the insulin resistance. Dyslipidemia in metabolic syndrome and diabetes mellitus features hypertriglycemia and low HDL cholesterolemia. The lipoprotein of triglycerides is consisted of mainly high remnant and VLDL lipoprotein. In addition, small dense LDL appears in these state. Small dense LDL is a high risk for atherosclerosis. For a treatment strategy, not only drug treatment such as fibrates, anti-diabetic drug, but we pay attention to visceral fat accumulation, and stratificate pathologically to appropriate treatment orientation. Early lifestyle intervention for example health instruction should be needed. PMID:24205723

  16. Human metabolic atlas: an online resource for human metabolism.

    PubMed

    Pornputtapong, Natapol; Nookaew, Intawat; Nielsen, Jens

    2015-01-01

    Human tissue-specific genome-scale metabolic models (GEMs) provide comprehensive understanding of human metabolism, which is of great value to the biomedical research community. To make this kind of data easily accessible to the public, we have designed and deployed the human metabolic atlas (HMA) website (http://www.metabolicatlas.org). This online resource provides comprehensive information about human metabolism, including the results of metabolic network analyses. We hope that it can also serve as an information exchange interface for human metabolism knowledge within the research community. The HMA consists of three major components: Repository, Hreed (Human REaction Entities Database) and Atlas. Repository is a collection of GEMs for specific human cell types and human-related microorganisms in SBML (System Biology Markup Language) format. The current release consists of several types of GEMs: a generic human GEM, 82 GEMs for normal cell types, 16 GEMs for different cancer cell types, 2 curated GEMs and 5 GEMs for human gut bacteria. Hreed contains detailed information about biochemical reactions. A web interface for Hreed facilitates an access to the Hreed reaction data, which can be easily retrieved by using specific keywords or names of related genes, proteins, compounds and cross-references. Atlas web interface can be used for visualization of the GEMs collection overlaid on KEGG metabolic pathway maps with a zoom/pan user interface. The HMA is a unique tool for studying human metabolism, ranging in scope from an individual cell, to a specific organ, to the overall human body. This resource is freely available under a Creative Commons Attribution-NonCommercial 4.0 International License. PMID:26209309

  17. Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

    PubMed Central

    Baart, Gino JE; Zomer, Bert; de Haan, Alex; van der Pol, Leo A; Beuvery, E Coen; Tramper, Johannes; Martens, Dirk E

    2007-01-01

    Background Neisseria meningitidis is a human pathogen that can infect diverse sites within the human host. The major diseases caused by N. meningitidis are responsible for death and disability, especially in young infants. In general, most of the recent work on N. meningitidis focuses on potential antigens and their functions, immunogenicity, and pathogenicity mechanisms. Very little work has been carried out on Neisseria primary metabolism over the past 25 years. Results Using the genomic database of N. meningitidis serogroup B together with biochemical and physiological information in the literature we constructed a genome-scale flux model for the primary metabolism of N. meningitidis. The validity of a simplified metabolic network derived from the genome-scale metabolic network was checked using flux-balance analysis in chemostat cultures. Several useful predictions were obtained from in silico experiments, including substrate preference. A minimal medium for growth of N. meningitidis was designed and tested succesfully in batch and chemostat cultures. Conclusion The verified metabolic model describes the primary metabolism of N. meningitidis in a chemostat in steady state. The genome-scale model is valuable because it offers a framework to study N. meningitidis metabolism as a whole, or certain aspects of it, and it can also be used for the purpose of vaccine process development (for example, the design of growth media). The flux distribution of the main metabolic pathways (that is, the pentose phosphate pathway and the Entner-Douderoff pathway) indicates that the major part of pyruvate (69%) is synthesized through the ED-cleavage, a finding that is in good agreement with literature. PMID:17617894

  18. Human metabolic atlas: an online resource for human metabolism

    PubMed Central

    Nookaew, Intawat; Nielsen, Jens

    2015-01-01

    Human tissue-specific genome-scale metabolic models (GEMs) provide comprehensive understanding of human metabolism, which is of great value to the biomedical research community. To make this kind of data easily accessible to the public, we have designed and deployed the human metabolic atlas (HMA) website (http://www.metabolicatlas.org). This online resource provides comprehensive information about human metabolism, including the results of metabolic network analyses. We hope that it can also serve as an information exchange interface for human metabolism knowledge within the research community. The HMA consists of three major components: Repository, Hreed (Human REaction Entities Database) and Atlas. Repository is a collection of GEMs for specific human cell types and human-related microorganisms in SBML (System Biology Markup Language) format. The current release consists of several types of GEMs: a generic human GEM, 82 GEMs for normal cell types, 16 GEMs for different cancer cell types, 2 curated GEMs and 5 GEMs for human gut bacteria. Hreed contains detailed information about biochemical reactions. A web interface for Hreed facilitates an access to the Hreed reaction data, which can be easily retrieved by using specific keywords or names of related genes, proteins, compounds and cross-references. Atlas web interface can be used for visualization of the GEMs collection overlaid on KEGG metabolic pathway maps with a zoom/pan user interface. The HMA is a unique tool for studying human metabolism, ranging in scope from an individual cell, to a specific organ, to the overall human body. This resource is freely available under a Creative Commons Attribution-NonCommercial 4.0 International License. Database URL: http://www.metabolicatlas.org. PMID:26209309

  19. Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

    PubMed Central

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-01-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. PMID:25344492

  20. Redesigned Human Metabolic Simulator

    NASA Technical Reports Server (NTRS)

    Duffield, Bruce; Jeng, Frank; Lange, Kevin

    2008-01-01

    A design has been formulated for a proposed improved version of an apparatus that simulates atmospheric effects of human respiration by introducing controlled amounts of carbon dioxide, water vapor, and heat into the air. Denoted a human metabolic simulator (HMS), the apparatus is used for testing life-support equipment when human test subjects are not available. The prior version of the HMS, to be replaced, was designed to simulate the respiratory effects of as many as four persons. It exploits the catalytic combustion of methyl acetate, for which the respiratory quotient (the molar ratio of carbon dioxide produced to oxygen consumed) is very close to the human respiratory quotient of about 0.86. The design of the improved HMS provides for simulation of the respiratory effects of as many as eight persons at various levels of activity. The design would also increase safety by eliminating the use of combustion. The improved HMS (see figure) would include a computer that would exert overall control. The computer would calculate the required amounts of oxygen removal, carbon dioxide addition, water addition, and heat addition by use of empirical equations for metabolic profiles of respiration and heat. A blower would circulate air between the HMS and a chamber containing a life-support system to be tested. With the help of feedback from a mass flowmeter, the blower speed would be adjusted to regulate the rate of flow according to the number of persons to be simulated and to a temperature-regulation requirement (the air temperature would indirectly depend on the rate of flow, among other parameters). Oxygen would be removed from the circulating air by means of a commercially available molecular sieve configured as an oxygen concentrator. Oxygen, argon, and trace amounts of nitrogen would pass through a bed in the molecular sieve while carbon dioxide, the majority of nitrogen, and other trace gases would be trapped by the bed and subsequently returned to the chamber. If

  1. COMMONALITIES IN METABOLISM OF ARSENICALS

    EPA Science Inventory

    Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with e...

  2. Tetrapyrrole Metabolism in Arabidopsis thaliana

    PubMed Central

    Tanaka, Ryouichi; Kobayashi, Koichi; Masuda, Tatsuru

    2011-01-01

    Higher plants produce four classes of tetrapyrroles, namely, chlorophyll (Chl), heme, siroheme, and phytochromobilin. In plants, tetrapyrroles play essential roles in a wide range of biological activities including photosynthesis, respiration and the assimilation of nitrogen/sulfur. All four classes of tetrapyrroles are derived from a common biosynthetic pathway that resides in the plastid. In this article, we present an overview of tetrapyrrole metabolism in Arabidopsis and other higher plants, and we describe all identified enzymatic steps involved in this metabolism. We also summarize recent findings on Chl biosynthesis and Chl breakdown. Recent advances in this field, in particular those on the genetic and biochemical analyses of novel enzymes, prompted us to redraw the tetrapyrrole metabolic pathways. In addition, we also summarize our current understanding on the regulatory mechanisms governing tetrapyrrole metabolism. The interactions of tetrapyrrole biosynthesis and other cellular processes including the plastid-to-nucleus signal transduction are discussed. PMID:22303270

  3. Metabolic energy required for flight

    NASA Technical Reports Server (NTRS)

    Lane, H. W.; Gretebeck, R. J.

    1994-01-01

    This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in spaced and their roles in energy metabolism during space flight.

  4. Deep epistasis in human metabolism

    PubMed Central

    Imielinski, Marcin; Belta, Calin

    2010-01-01

    We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing “deep” epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets. PMID:20590333

  5. Deep epistasis in human metabolism

    NASA Astrophysics Data System (ADS)

    Imielinski, Marcin; Belta, Calin

    2010-06-01

    We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing "deep" epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets.

  6. Metabolic depression: a historical perspective.

    PubMed

    Withers, Philip C; Cooper, Christine E

    2010-01-01

    An extended period of inactivity and reduced metabolic rate of many animals and plants, as well as unicellular organisms, has long been recognized by natural historians, e.g., Aristotle and Pliny. Biologists have studied this phenomenon since the 1550s (Gessner) and 1700s (Van Leeuwenhoek, Buffon). The period of inactivity can be less than a day, a few consecutive days or weeks, an entire season, or even many years. It can involve very different physiological states in response to a variety of environmental stimuli, such as extreme temperatures or unavailability of food or water. These periods of inactivity have been described and classified according to the group of organisms in question, extent and duration of the metabolic depression, ambient and body temperatures, state of body water (frozen or hyperosmotic), or availability of oxygen. Cryptobiosis, or "hidden life," is an extreme form of inactivity, with often complete cessation of metabolism. It was first described in the 1700s, was further characterized in the 1800s, and in the 1900s physiological studies delineated the extent of metabolic depression. Molecular mechanisms for cryptobiosis have been sought since the late 1900s. Cryptobiosis includes three physiological states, anhydrobiosis (desiccation), osmobiosis (high osmotic concentration), and cryobiosis (freezing), where metabolic depression is associated with an altered physical state of cell water and often involves accumulation of compatible solutes, and one physiological state, anoxybiosis (anoxia), where metabolic depression occurs at the normal cellular hydration state. Dormancy (torpor) is a less extreme form of inactivity, associated with a moderate reduction in metabolic rate (hypometabolism). Although first described by Aristotle and Pliny, studies in the 1900s delineated the basic physiological changes that accompany dormancy. Dormancy allows avoidance of unfavorable short- or long-term climatic conditions and conservation of energy and

  7. Metabolism and biochemistry in hypogravity

    NASA Technical Reports Server (NTRS)

    Leach, Carolyn S.

    1991-01-01

    The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

  8. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  9. Clocks, Metabolism, and the Epigenome

    PubMed Central

    Feng, Dan; Lazar, Mitchell A.

    2012-01-01

    Many behaviors and physiological activities in living organisms display circadian rhythms, allowing them to anticipate and prepare for the diurnal changes in the living environment. In this way, metabolic processes are aligned with the periodic environmental changes and behavioral cycles, such as the sleep/wake and fasting/feeding cycles. Disturbances of this alignment significantly increase the risk of metabolic diseases. Meanwhile, the circadian clock receives signals from the environment and feedback from metabolic pathways, and adjusts its activity and function. Growing evidence connects the circadian clock with epigenomic regulators. Here we review the recent advances in understanding the crosstalk between the circadian clock and energy metabolism through epigenomic programming and transcriptional regulation. PMID:22841001

  10. Protein metabolism and requirements.

    PubMed

    Biolo, Gianni

    2013-01-01

    Skeletal muscle adaptation to critical illness includes insulin resistance, accelerated proteolysis, and increased release of glutamine and the other amino acids. Such amino acid efflux from skeletal muscle provides precursors for protein synthesis and energy fuel to the liver and to the rapidly dividing cells of the intestinal mucosa and the immune system. From these adaptation mechanisms, severe muscle wasting, glutamine depletion, and hyperglycemia, with increased patient morbidity and mortality, may ensue. Protein/amino acid nutrition, through either enteral or parenteral routes, plays a pivotal role in treatment of metabolic abnormalities in critical illness. In contrast to energy requirement, which can be accurately assessed by indirect calorimetry, methods to determine individual protein/amino acid needs are not currently available. In critical illness, a decreased ability of protein/amino acid intake to promote body protein synthesis is defined as anabolic resistance. This abnormality leads to increased protein/amino acid requirement and relative inefficiency of nutritional interventions. In addition to stress mediators, immobility and physical inactivity are key determinants of anabolic resistance. The development of mobility protocols in the intensive care unit should be encouraged to enhance the efficacy of nutrition. In critical illness, protein/amino acid requirement has been defined as the intake level associated with the lowest rate of catabolism. The optimal protein-sparing effects in patients receiving adequate energy are achieved when protein/amino acids are administered at rates between 1.3 and 1.5 g/kg/day. Extra glutamine supplementation is required in conditions of severe systemic inflammatory response. Protein requirement increases during hypocaloric feeding and in patients with acute renal failure on continuous renal replacement therapy. Evidence suggests that receiving adequate protein/amino acid intake may be more important than achieving

  11. Glycogen metabolism in humans.

    PubMed

    Adeva-Andany, María M; González-Lucán, Manuel; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Ameneiros-Rodríguez, Eva

    2016-06-01

    In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5'-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases. PMID:27051594

  12. [Metabolic intolerance to exercise].

    PubMed

    Arenas, J; Martín, M A

    2003-01-01

    Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC. PMID:12838448

  13. Testosterone and metabolic syndrome

    PubMed Central

    Cunningham, Glenn R

    2015-01-01

    Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS). Many of the components are accepted risk factors for cardiovascular disease (CVD). Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT) and sex hormone binding globulin (SHBG) levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels. PMID:25652634

  14. Metabolism of Monoterpenes

    PubMed Central

    Croteau, Rodney; Martinkus, Charlott

    1979-01-01

    (−)-Menthone, the major monoterpene component of the essential oil of maturing peppermint (Mentha piperita L.) leaves (6 micromoles per leaf) is rapidly metabolized at the onset of flowering with a concomitant rise in the level of (−)-menthol (to about 2 micromoles per leaf). Exogenous (−)-[G-3H]menthone is converted into (−)-[3H]menthol as the major steam-volatile product in leaf discs in flowering peppermint (10% of incorporated tracer); however, the major portion of the incorporated tracer (86%) resided in the nonvolatile metabolites of (−)-[G-3H]menthone. Acid hydrolysis of the nonvolatile material released over half of the radioactivity to the steamvolatile fraction, and the major component of this fraction was identified as (+)-neomenthol by radiochromatographic analysis and by synthesis of crystalline derivatives, thus suggesting the presence of a neomenthyl glycoside. Thin layer chromatography, ion exchange chromatography, and gel permeation chromatography on Bio-Gel P-2 allowed the purification of the putative neomenthyl glycoside, and these results suggested that the glycoside contained a single, neutral sugar residue. Hydrolysis of the purified glycoside, followed by reduction of the resulting sugar moiety with NaB3H4, generated a single labeled product that was subsequently identified as glucitol by radio gas-liquid chromatography of both the hexatrimethylsilyl ether and hexaacetate derivative, and by crystallization to constant specific radioactivity of both the alditol and the corresponding hexabenzoate. These results, along with studies on the hydrolysis of the glycoside by specific glycosidases, strongly suggest that (+)-neomenthyl-β-d-glucoside is a major metabolite of (−)-menthone in flowering peppermint. This is the first report on the occurrence of a neomenthyl glycoside, and the first evidence implicating glycosylation as an early step in monoterpene catabolism. PMID:16660926

  15. Metabolism of Monoterpenes

    PubMed Central

    Croteau, Rodney; Hooper, Caroline Lee

    1978-01-01

    The essential oil from mature leaves of flowering peppermint (Mentha piperita L.) contains up to 15% (—)-menthyl acetate, and leaf discs converted exogenous (—)-[G-3H]menthol into this ester in approximately 15% yield of the incorporated precursor. Leaf extracts catalyzed the acetyl coenzyme A-dependent acetylation of (—)-[G-3H]menthol and the product of this transacetylase reaction was identified by radiochromatographic techniques. Transacetylase activity was located mainly in the 100,000g supernatant fraction, and the preparation was partially purified by combination of Sephadex G-100 gel filtration and chromatography on O-diethylaminoethyl-cellulose. The transacetylase had a molecular weight of about 37,000 as judged by Sephadex G-150 gel filtration, and a pH optimum near 9. The apparent Km and velocity for (—)-menthol were 0.3 mm and 16 nmol/hr· mg of protein, respectively. The saturation curve for acetyl coenzyme A was sigmoidal, showing apparent saturation near 0.1 mm. Dithioerythritol was required for maximum activity and stability of the enzyme, and the enzyme was inhibited by thiol directed reagents such as p-hydroxymercuribenzoate. Diisopropylfluorophosphate also inhibited transacylation suggesting the involvement of a serine residue in catalysis. The transacylase was highly specific for acetyl coenzyme A; propionyl coenzyme A and butyryl coenzyme A were not nearly as efficient as acyl donors (11% and 2%, respectively). However, the enzyme was much less selective with regard to the alcohol substrate, suggesting that the nature of the acetate ester synthesized in mint is more dependent on the type of alcohol available than on the specificity of the transacetylase. This is the first report on an enzyme involved in monoterpenol acetylation in plants. A very similar enzyme, catalyzing this key reaction in the metabolism of menthol, was also isolated from the flowers of peppermint. PMID:16660375

  16. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  17. Thyroid Cancer Metabolism: A Review

    PubMed Central

    Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M

    2016-01-01

    Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems. PMID:27213120

  18. [Metabolic therapy for heart failure].

    PubMed

    Loiacono, Ferdinando; Alberti, Luca; Lauretta, Ludovica; Puccetti, Patrizia; Silipigni, Carmen; Margonato, Alberto; Fragasso, Gabriele

    2014-01-01

    Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary. PMID:25072544

  19. Ocular Metabolism of Levobunolol: Historic and Emerging Metabolic Pathways.

    PubMed

    Argikar, Upendra A; Dumouchel, Jennifer L; Dunne, Christine E; Saran, Chitra; Cirello, Amanda L; Gunduz, Mithat

    2016-08-01

    Although ocular transport and delivery have been well studied, metabolism in the eye is not well documented, even for clinically available medications such as levobunolol, a potent and nonselective β-adrenergic receptor antagonist. Recently, we reported an in vitro methodology that could be used to evaluate ocular metabolism across preclinical species and humans. The current investigation provides detailed in vitro ocular and liver metabolism of levobunolol in rat, rabbit, and human S9 fractions, including the formation of equipotent active metabolite, dihydrolevobunolol, with the help of high-resolution mass spectrometry. 11 of the 16 metabolites of levobunolol identified herein, including a direct acetyl conjugate of levobunolol observed in all ocular and liver fractions, have not been reported in the literature. The study documents the identification of six human ocular metabolites that have never been reported. The current investigation presents evidence for ocular and hepatic metabolism of levobunolol via non-cytochrome P450 pathways, which have not been comprehensively investigated to date. Our results indicated that rat liver S9 and human ocular S9 fractions formed the most metabolites. Furthermore, liver was a poor in vitro surrogate for eye, and rat and rabbit were poor surrogates for human in terms of the rate and extent of levobunolol metabolism. PMID:27190057

  20. Unfamiliar metabolic links in the central carbon metabolism.

    PubMed

    Fuchs, Georg; Berg, Ivan A

    2014-12-20

    The central carbon metabolism of all organisms is considered to follow a well established fixed scheme. However, recent studies of autotrophic carbon fixation in prokaryotes revealed unfamiliar metabolic links. A new route interconnects acetyl-coenzyme A (CoA) via 3-hydroxypropionate with succinyl-CoA. Succinyl-CoA in turn may be metabolized via 4-hydroxybutyrate to two molecules of acetyl-CoA; a reversal of this route would result in the assimilation of two molecules of acetyl-CoA into C4 compounds. C5-dicarboxylic acids are a rather neglected class of metabolites; yet, they play a key role not only in one of the CO2 fixation cycles, but also in two acetate assimilation pathways that replace the glyoxylate cycle. C5 compounds such as ethylmalonate, methylsuccinate, methylmalate, mesaconate, itaconate and citramalate or their CoA esters are thereby linked to the acetyl-CoA, propionyl-CoA, glyoxylate and pyruvate pools. A novel carboxylase/reductase converts crotonyl-CoA into ethylmalonyl-CoA; similar reductive carboxylations apply to other alpha-beta-unsaturated carboxy-CoA thioesters. These unfamiliar metabolic links may provide useful tools for metabolic engineering. PMID:24576434

  1. Triglyceride Metabolism and Hepatic Diseases.

    PubMed

    Fernandez-Mejia, Emptyyn Y

    2013-09-11

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplasticcells. One of the main medical concerns vis-à-vishepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24032513

  2. Drug metabolism and chemosensitization. Nitroimidazoles as inhibitors of drug metabolism.

    PubMed

    Workman, P; Twentyman, P R; Lee, F Y; Walton, M I

    1983-03-01

    The nitroimidazole misonidazole (MISO) and related compounds have been shown to enhance the response of tumours to cytotoxic agents, and often to improve their therapeutic indices. Previous experiments suggested inhibition of cytotoxic drug metabolism as a mechanism. We have now investigated the effects of MISO and related compounds on drug metabolism in mice, and the results can be summarised as follows. (1) MISO and related compounds inhibit drug-metabolising enzymes, as measured by pentobarbitone sleep-time and zoxazolamine paralysis-time. (2) Enzyme inhibition is primarily dependent on lipophilicity, with maximum inhibition exhibited by the most active chemosensitizers. (3) MISO significantly slowed the clearance of pentobarbitone, aminopyrine and the cytotoxic agent chlorambucil, but had no effect on renal function or protein binding. These data support the view that inhibition of cytotoxic drug metabolism may be an important factor in chemosensitization. PMID:6838633

  3. Metabolic Cost of Experimental Exercises

    NASA Technical Reports Server (NTRS)

    Webb, James T.; Gernhardt, Michael L.

    2009-01-01

    Although the type and duration of activity during decompression was well documented, the metabolic cost of 1665 subject-exposures with 8 activity profiles from 17 altitude decompression sickness (DCS) protocols at Brooks City-Base, TX from 1983-2005 was not determined. Female and male human volunteers (30 planned, 4 completed) performed activity profiles matching those 8 activity profiles at ground level with continuous monitoring of metabolic cost. A Cosmed K4b2 Cardio Pulmonary Exercise Testing device was used to measure oxygen uptake (VO2) during the profiles. The results show levels of metabolic cost to the females for the profiles tested varied from 4.3 to 25.5 ml/kg/min and from 3.0 to 12.0 ml/kg/min to the males. The increase in VO2 from seated rest to the most strenuous of the 8 activity profiles was 3.6-fold for the females and 2.8-fold for the males. These preliminary data on 4 subjects indicate close agreement of oxygen uptake for activity performed during many subject-exposures as published earlier. The relatively low average oxygen uptake required to perform the most strenuous activity may imply the need for adjustment of modeling efforts using metabolic cost as a risk factor. Better definition of metabolic cost during exposure to altitude, a critical factor in DCS risk, may allow refinement of DCS prediction models.

  4. Sirtuin and metabolic kidney disease

    PubMed Central

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-01-01

    Sirtuin is a nicotinamide adenine dinucleotide–dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti–fibrosis effects, anti–oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule–specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy. PMID:26083654

  5. MPW : the metabolic pathways database.

    SciTech Connect

    Selkov, E., Jr.; Grechkin, Y.; Mikhailova, N.; Selkov, E.; Mathematics and Computer Science; Russian Academy of Sciences

    1998-01-01

    The Metabolic Pathways Database (MPW) (www.biobase.com/emphome.html/homepage. html.pags/pathways.html) a derivative of EMP (www.biobase.com/EMP) plays a fundamental role in the technology of metabolic reconstructions from sequenced genomes under the PUMA (www.mcs.anl.gov/home/compbio/PUMA/Production/ ReconstructedMetabolism/reconstruction.html), WIT (www.mcs.anl.gov/home/compbio/WIT/wit.html ) and WIT2 (beauty.isdn.msc.anl.gov/WIT2.pub/CGI/user.cgi) systems. In October 1997, it included some 2800 pathway diagrams covering primary and secondary metabolism, membrane transport, signal transduction pathways, intracellular traffic, translation and transcription. In the current public release of MPW (beauty.isdn.mcs.anl.gov/MPW), the encoding is based on the logical structure of the pathways and is represented by the objects commonly used in electronic circuit design. This facilitates drawing and editing the diagrams and makes possible automation of the basic simulation operations such as deriving stoichiometric matrices, rate laws, and, ultimately, dynamic models of metabolic pathways. Individual pathway diagrams, automatically derived from the original ASCII records, are stored as SGML instances supplemented by relational indices. An auxiliary database of compound names and structures, encoded in the SMILES format, is maintained to unambiguously connect the pathways to the chemical structures of their intermediates.

  6. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  7. Metabolic acceleration in Mediterranean Perciformes

    NASA Astrophysics Data System (ADS)

    Lika, Konstadia; Kooijman, Sebastiaan A. L. M.; Papandroulakis, Nikos

    2014-11-01

    Larval stages are considered the most critical of fish development. During a very short period of time (2 to 3 months), larvae undergo major morphoanatomical and functional changes in order to transform into juveniles while remaining functioning (developing, eating, surviving). Depending on species and environmental conditions, patterns in larval development may vary. We study the patterns of larval development for nine fish species of Perciformes reared under aquaculture conditions and compare them in terms of species-specific parameters derived from DEB theory. We extended the standard DEB model to include metabolic acceleration during the larval period, where maximum specific assimilation and energy conductance increase with length between birth and metabolic metamorphosis. Metabolic acceleration has as a consequence that larvae initially grow slower than juveniles and adults. Our results indicate that the species with higher acceleration have lower growth rates at birth and they also suggest that metabolic acceleration is related to spawning season. High metabolic acceleration of demersal species is associated with summer-autumn spawning in the Mediterranean, where temperature is high and food availability is low.

  8. Gut microbiota and metabolic syndrome

    PubMed Central

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-01-01

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

  9. Mathematical Modeling of Cellular Metabolism.

    PubMed

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research. PMID:27557541

  10. Leucine metabolism in human newborns

    SciTech Connect

    Denne, S.C.; Kalhan, S.C. )

    1987-12-01

    The present study was designed to (1) determine whether a relationship exists between newborn birth weight and leucine metabolism and (2) compare leucine and energy metabolism in a period of rapid growth and development (i.e., newborn) with a constant nongrowth period (i.e., adult). Leucine kinetics and energy expenditure were measured in the postabsorptive state in 12 normal full-term newborns in early neonatal life and in 11 normal adults using a primed constant L-(1-{sup 13}C)leucine infusion combined with respiratory calorimetry. A significant positive correlation between newborn birth weight and leucine flux was observed. These data suggest the following. (1) A relationship exists between newborn birth weight and protein metabolism, as reflected by the correlation between leucine flux when expressed as micromoles per kilogram per hour and birth weight. (2) The high rate of leucine flux measured in newborns probably reflects the rapid remodeling of protein that occurs in this period of development, even during fasting. (3) The similar values in newborns and adults of leucine kinetics and energy expenditure when normalized to metabolic body weight and the nearly equivalent allometric exponents relating body weight to leucine flux and energy expenditure support a close relationship between leucine and energy metabolism, at least at the extremes of human growth.

  11. Lipid metabolism in mitochondrial membranes.

    PubMed

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  12. Videofluorometer for imaging tissue metabolism

    NASA Astrophysics Data System (ADS)

    Kelly, Jeffrey J.; Rorvik, Dawn A.; Richmond, Keith N.; Barlow, Clyde H.

    1989-11-01

    A videofluorometer is described that directly acquires digital metabolic images of reduced nicotinamide adenine dinucleotide (NADH) fluorescence in tissue. NADH fluorescence provides an intrinsic indicator of the state of tissue mitochondrial oxidative metabolism. The device combines a computer-controlled fluorescence excitation system with digital image acquisition to quantify tissue bioenergetics in both spatial and time domains. Localized ischemia following coronary artery ligation in a perfused rat heart (model for a coronary artery occlusion heart attack) is used as an example to demonstrate the capabilities of the system. This videofluorometer permits monitoring changes in physiological state of organs and tissue without interfering with tissue metabolism. The digital nature of the acquired image allows detailed analysis of physiological features and their time dependence.

  13. [Atypical antipsychotics and metabolic syndrome].

    PubMed

    Baranyi, Andreas; Yazdani, Renè; Haas-Krammer, Alexandra; Stepan, Alexandra; Kapfhammer, Hans-Peter; Rothenhäusler, Hans-Bernd

    2007-01-01

    The introduction of atypical antipsychotics in psychopharmacology represented a major advance in the treatment of psychotic disorders. However, there have been numerous studies that certain atypical antipsychotics may be associated with a greater risk of metabolic abnormalities than others, including weight gain, hyperlipidemia and new-onset typ 2 diabetes mellitus. A G-Protein beta3 subunit Gen (C825T) polymorphism, an increased carbohydrate metabolism and dyshormonism are discussed as pathogenetic mechanisms. High risk patients (adiposity, hyperlipidaemia, hyperglycaemia, preexisting diabetes) should maintain an antipsychotic agent with a favourable side effect profile. In these cases a periodical diabetes screening and blood lipid controls are required. Clinicans must balance the significant benefits of atypical antipsychotics against the risk of metabolic disturbances. In this article recent findings are reviewed. PMID:17915438

  14. Public goods and metabolic strategies.

    PubMed

    Bachmann, Herwig; Bruggeman, Frank J; Molenaar, Douwe; Branco Dos Santos, Filipe; Teusink, Bas

    2016-06-01

    Microbial growth can be characterized by a limited set of macroscopic parameters such as growth rate, biomass yield and substrate affinity. Different culturing protocols for laboratory evolution have been developed to select mutant strains that have one specific macroscopic growth parameter improved. Some of those mutant strains display tradeoffs between growth parameters and changed metabolic strategies, for example, a shift from respiration to fermentation. Here we discuss recent studies suggesting that metabolic strategies and growth parameter tradeoffs originate from a common set of physicochemical and cellular constraints, associated with the allocation of intracellular resources over biosynthetic processes, mostly protein synthesis. This knowledge will give insight in ecological and biological concepts and can be used for metabolic and evolutionary engineering strategies. PMID:27054480

  15. Manufacturing molecules through metabolic engineering.

    PubMed

    Keasling, Jay D

    2010-12-01

    Metabolic engineering has the potential to produce from simple, readily available, inexpensive starting materials a large number of chemicals that are currently derived from nonrenewable resources or limited natural resources. Microbial production of natural products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered, and production of unnatural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism and by engineering enzymes to have new function. Whereas existing production routes use well-known, safe, industrial microorganisms, future production schemes may include designer cells that are tailor-made for the desired chemical and production process. In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry. PMID:21127247

  16. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  17. Thyroid Hormone Regulation of Metabolism

    PubMed Central

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

  18. Complexity of vitamin E metabolism.

    PubMed

    Schmölz, Lisa; Birringer, Marc; Lorkowski, Stefan; Wallert, Maria

    2016-02-26

    Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for

  19. Complexity of vitamin E metabolism

    PubMed Central

    Schmölz, Lisa; Birringer, Marc; Lorkowski, Stefan; Wallert, Maria

    2016-01-01

    Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for

  20. Epigenetic regulation of skeletal muscle metabolism.

    PubMed

    Howlett, Kirsten F; McGee, Sean L

    2016-07-01

    Normal skeletal muscle metabolism is essential for whole body metabolic homoeostasis and disruptions in muscle metabolism are associated with a number of chronic diseases. Transcriptional control of metabolic enzyme expression is a major regulatory mechanism for muscle metabolic processes. Substantial evidence is emerging that highlights the importance of epigenetic mechanisms in this process. This review will examine the importance of epigenetics in the regulation of muscle metabolism, with a particular emphasis on DNA methylation and histone acetylation as epigenetic control points. The emerging cross-talk between metabolism and epigenetics in the context of health and disease will also be examined. The concept of inheritance of skeletal muscle metabolic phenotypes will be discussed, in addition to emerging epigenetic therapies that could be used to alter muscle metabolism in chronic disease states. PMID:27215678

  1. Exploiting tumor metabolism: challenges for clinical translation

    PubMed Central

    Vander Heiden, Matthew G.

    2013-01-01

    The metabolism of cancer cells differs from most normal cells, but how to exploit this difference for patient benefit is incompletely understood. Cancer cells require altered metabolism to efficiently incorporate nutrients into biomass and support abnormal proliferation. In addition, the survival of tumor cells outside of a normal tissue context requires adaptation of metabolism to different microenvironments. Some existing chemotherapies target metabolic enzymes, and there is a resurgent interest in developing new cancer drugs that interfere with metabolism. Success with this approach depends on understanding why specific metabolic pathways are important for cancer cells, determining how best to select patients, and developing technologies for monitoring patient response to therapies that target metabolic enzymes. The articles in this Review series address these issues, with a focus on how altered metabolism might influence tumor progression and how this knowledge might inform the use of new therapies targeting cancer metabolism. Emerging biomarker strategies to guide drug development are also highlighted. PMID:23999437

  2. Imaging and Modeling of Myocardial Metabolism

    PubMed Central

    Jamshidi, Neema; Karimi, Afshin; Birgersdotter-Green, Ulrika; Hoh, Carl

    2010-01-01

    Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed. PMID:20559785

  3. Magnesium metabolism: a brief review.

    PubMed Central

    Paymaster, N. J.

    1976-01-01

    The important role played by the magnesium ion in the body is not generally recognized. The action of numerous enzyme systems critical to cellular metabolism is regulated by it and it contributes importantly to macromolecular structure. Magnesium defiency occurs more often than is generally suspected; magnesium excess, though uncommon, is of special interest to the anaesthetist because it produces a curare-like effect on neuromuscular transmission. It is hoped that this brief review of magnesium metabolism will draw attention to its importance and relevance in everyday practice. PMID:942168

  4. [Glucose metabolic changes in stress].

    PubMed

    Foia, L; Costuleanu, N; Trandafirescu, M; Saila, V; Pavel, M

    1999-01-01

    Provision of a better understanding of the pathogenic pathways underlying injured sugar metabolism during stress should ideally translate into a more rational approach to the provision of nutritional support. Patients with burns, trauma, severe injuries or infections commonly develop a hypermetabolic state that is associated with several changes in carbohydrate metabolism. The hypermetabolic state is induced either by the area of injury and by organs involved in the immunologic response to stress; further it determines a glycemic milieu which will be directed toward satisfaction of the requirements for glucose as an energy support. PMID:10756928

  5. [Metabolic therapy of postperitoneal intoxication].

    PubMed

    Vlasov, A P; Anaskin, S G; Vlasova, T I; Chivisov, S M; Shibitov, V A; Potyanova, I V; Selentsov, P V

    2012-01-01

    This clinico-laboratory study showed that antihypoxant remaxol promoted normalization of lipid metabolism in acute peritonitis and significantly reduced membrane-destabilizing events. This resulted in rapid elimination of the inflammatory process in the abdominal cavity and lowering of the intensity of endogenous intoxication. This beneficial effect decreased the severity of myocardial lesions and resulted in the normalization of erythrocyte function. It is concluded that the regulatory action of remaxol on lipid metabolism is due to its ability to control free radicals in lipid peroxidation and reduce phospholipase A2 activity. PMID:23285765

  6. Metabolism of verruculogen in rats.

    PubMed Central

    Perera, K P; Day, J B; Mantle, P G; Rodrigues, L

    1982-01-01

    Radiolabeled verruculogen was detected in a wide range of body tissues 6 min after intravenous administration, but after a further 20 min it was mainly being excreted via the biliary route. In isolated liver perfusion, [14C]verruculogen was rapidly taken up by the liver and metabolized completely, principally to the related tremorgen TR-2 but also to a desoxy derivative of verruculogen. In addition, a smaller amount of an isomer of TR-2 was detected. These metabolic products were excreted in the bile. PMID:7041818

  7. Metabolism of verruculogen in rats.

    PubMed

    Perera, K P; Day, J B; Mantle, P G; Rodrigues, L

    1982-03-01

    Radiolabeled verruculogen was detected in a wide range of body tissues 6 min after intravenous administration, but after a further 20 min it was mainly being excreted via the biliary route. In isolated liver perfusion, [14C]verruculogen was rapidly taken up by the liver and metabolized completely, principally to the related tremorgen TR-2 but also to a desoxy derivative of verruculogen. In addition, a smaller amount of an isomer of TR-2 was detected. These metabolic products were excreted in the bile. PMID:7041818

  8. Metabolic regulation of mitochondrial dynamics

    PubMed Central

    Mishra, Prashant

    2016-01-01

    Mitochondria are renowned for their central bioenergetic role in eukaryotic cells, where they act as powerhouses to generate adenosine triphosphate from oxidation of nutrients. At the same time, these organelles are highly dynamic and undergo fusion, fission, transport, and degradation. Each of these dynamic processes is critical for maintaining a healthy mitochondrial population. Given the central metabolic function of mitochondria, it is not surprising that mitochondrial dynamics and bioenergetics reciprocally influence each other. We review the dynamic properties of mitochondria, with an emphasis on how these processes respond to cellular signaling events and how they affect metabolism. PMID:26858267

  9. Metabolic phenotype of bladder cancer.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  10. Metabolic regulation via enzyme filamentation

    PubMed Central

    Aughey, Gabriel N.; Liu, Ji-Long

    2016-01-01

    Abstract Determining the mechanisms of enzymatic regulation is central to the study of cellular metabolism. Regulation of enzyme activity via polymerization-mediated strategies has been shown to be widespread, and plays a vital role in mediating cellular homeostasis. In this review, we begin with an overview of the filamentation of CTP synthase, which forms filamentous structures termed cytoophidia. We then highlight other important examples of the phenomenon. Moreover, we discuss recent data relating to the regulation of enzyme activity by compartmentalization into cytoophidia. Finally, we hypothesize potential roles for enzyme filament formation in the regulation of metabolism, development and disease. PMID:27098510

  11. Revealed aspect of metabolic osteoarthritis.

    PubMed

    Chadha, Rishmeen

    2016-12-01

    In current scenario there is an emerging trend to consider osteoarthritis (OA) phenotypes based on their risk factors and therefore offering potential for targeted therapies. OA prevalence with other coexistence diseases, such as systemic arterial hypertension, cardiovascular disease, diabetes, and dyslipidemia are increasing. Majority of OA associated with MetS, despite overweight of patients, the occurrence of OA in joints do not bear load suggest, the chronic inflammation status existing in patients with MetS can alter the metabolism of cartilage, regardless of excessive weight. This paper indicates that factors responsible for metabolic syndrome has clear role in cartilage degeneration and further degradation. PMID:27453640

  12. Cancer metabolism: current perspectives and future directions

    PubMed Central

    Muñoz-Pinedo, C; El Mjiyad, N; Ricci, J-E

    2012-01-01

    Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how ‘metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer′s ‘Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells. PMID:22237205

  13. Developmental changes in the activities of aromatic amino acid decarboxylase and catechol-O-methyl transferase in the porcine brain: a positron emission tomography study.

    PubMed

    Brust, Peter; Walter, Bernd; Hinz, Rainer; Füchtner, Frank; Müller, Marco; Steinbach, Jörg; Bauer, Reinhard

    2004-07-01

    Newborn (7-10 days old) and young (6-8 weeks old) pigs were used to study the metabolism of 6-[18F]fluoro-L-DOPA (FDOPA) in various brain regions with positron emission tomography (PET). Compartmental modeling of PET data was used to calculate the rate constants for the decarboxylation of FDOPA (k3) and for the metabolism of the resulting [18F]fluoro-dopamine (kcl). Whereas general physiological parameters such as cerebral blood flow, cerebral oxygen uptake, arterial blood gases and glucose concentration remained unchanged in young pigs as compared to newborns, a 50-200% increase of k3 in frontal cortex, striatum and mesencephalon was found. Also a 60% enhancement of kcl in the frontal cortex was measured, which is related to changes of the catechol-O-methyl-transferase (COMT) activity and implies a special function of this enzyme in the development of this brain region. In addition, measurement of plasma metabolites of FDOPA with HPLC was performed. The metabolism of FDOPA in young pigs was significantly faster than in newborns. Calculation of the rate constant for O-methylation of FDOPA by COMT revealed a significant elevation of this enzyme activity in young pigs compared to newborns. The increase of AADC and COMT activity with brain development is considered to be associated with special stages of neuronal maturation and tissue differentiation. PMID:15196667

  14. Computational Approaches for Understanding Energy Metabolism

    PubMed Central

    Shestov, Alexander A; Barker, Brandon; Gu, Zhenglong; Locasale, Jason W

    2013-01-01

    There has been a surge of interest in understanding the regulation of metabolic networks involved in disease in recent years. Quantitative models are increasingly being used to i nterrogate the metabolic pathways that are contained within this complex disease biology. At the core of this effort is the mathematical modeling of central carbon metabolism involving glycolysis and the citric acid cycle (referred to as energy metabolism). Here we discuss several approaches used to quantitatively model metabolic pathways relating to energy metabolism and discuss their formalisms, successes, and limitations. PMID:23897661

  15. Transcriptional coregulators: fine-tuning metabolism

    PubMed Central

    Mouchiroud, Laurent; Eichner, Lillian J.; Shaw, Reuben; Auwerx, Johan

    2014-01-01

    Metabolic homeostasis requires that cellular energy levels are adapted to environmental cues. This adaptation is largely regulated at the transcriptional level, through the interaction between transcription factors, coregulators, and the basal transcriptional machinery. Coregulators, which function both as metabolic sensors and transcriptional effectors, are ideally positioned to synchronize metabolic pathways to environmental stimuli. The balance between inhibitory actions of corepressors and stimulatory effects of coactivators enables the fine-tuning of metabolic processes. The tight regulation opens therapeutic opportunities to manage metabolic dysfunction, by directing the activity of cofactors towards specific transcription factors, pathways, or cells/tissues, thereby restoring whole body metabolic homeostasis. PMID:24794975

  16. An overview of benzene metabolism

    SciTech Connect

    Snyder, R.; Hedli, C.C.

    1996-12-01

    Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities; associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity. 52 refs., 9 figs., 5 tabs.

  17. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

    Peroxisomes are ubiquitous and multifunctional organelles that are primarily known for their role in cellular lipid metabolism. As many peroxisomal enzymes catalyze redox reactions as part of their normal function, these organelles are also increasingly recognized as potential regulators of oxidative stress-related signaling pathways. This in turn suggests that peroxisome dysfunction is not only associated with rare inborn errors of peroxisomal metabolism, but also with more common age-related diseases such as neurodegeneration, type 2 diabetes, and cancer. This review intends to provide a comprehensive picture of the complex role of mammalian peroxisomes in cellular redox metabolism. We highlight how peroxisomal metabolism may contribute to the bioavailability of important mediators of oxidative stress, with particular emphasis on reactive oxygen species. In addition, we review the biological properties of peroxisome-derived signaling messengers and discuss how these molecules may mediate various biological responses. Furthermore, we explore the emerging concepts that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. This is particularly relevant to the observed demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases. PMID:23933092

  18. Sex Hormones and Macronutrient Metabolism

    PubMed Central

    Comitato, Raffaella; Saba, Anna; Turrini, Aida; Arganini, Claudia; Virgili, Fabio

    2015-01-01

    The biological differences between males and females are determined by a different set of genes and by a different reactivity to environmental stimuli, including the diet, in general. These differences are further emphasized and driven by the exposure to a different hormone flux throughout the life. These differences have not been taken into appropriate consideration by the scientific community. Nutritional sciences are not immune from this “bias” and when nutritional needs are concerned, females are considered only when pregnant, lactating or when their hormonal profile is returning back to “normal,” i.e., to the male-like profile. The authors highlight some of the most evident differences in aspects of biology that are associated with nutrition. This review presents and describes available data addressing differences and similarities of the “reference man” vs. the “reference woman” in term of metabolic activity and nutritional needs. According to this assumption, available evidences of sex-associated differences of specific biochemical pathways involved in substrate metabolism are reported and discussed. The modulation by sexual hormones affecting glucose, amino acid and protein metabolism and the metabolization of nutritional fats and the distribution of fat depots, is considered targeting a tentative starting up background for a gender concerned nutritional science. PMID:24915409

  19. Metabolic rate meter and method

    NASA Technical Reports Server (NTRS)

    Taylor, T. I.; Ruderman, I. W. (Inventor)

    1968-01-01

    A method is described for measuring the dynamic metabolic rate of a human or animal. The ratio of the exhaled carbon dioxide to a known amount of C(13)02 introduced into the exhalation is determined by mass spectrometry. This provides an instantaneous measurement of the carbon dioxide generated.

  20. Does Metabolically Healthy Obesity Exist?

    PubMed Central

    Muñoz-Garach, Araceli; Cornejo-Pareja, Isabel; Tinahones, Francisco J.

    2016-01-01

    The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of “more fat means more metabolic disease”, and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID:27258304

  1. Tumor Mechanics and Metabolic Dysfunction

    PubMed Central

    Tung, Jason C.; Barnes, J. Matthew; Desai, Shraddha R.; Sistrunk, Christopher; Conklin, Matthew; Schedin, Pepper; Keely, Patricia J.; Seewaldt, Victoria L.; Weaver, Valerie M.

    2015-01-01

    Desmosplasia is a characteristic of most solid tumors and leads to fibrosis through abnormal extracellular matrix (ECM) deposition, remodeling and post translational modifications. The resulting stiff tumor stroma not only compromises vascular integrity to induce hypoxia and impede drug delivery, but also promotes aggressiveness by potentiating the activity of key growth, invasion, and survival pathways. Intriguingly, many of the pro-tumorigenic signaling pathways which are mechanically activated by ECM stiffness also promote glucose uptake and aerobic glycolysis, and an altered metabolism is a recognized hallmark of cancer. Indeed, emerging evidence suggests that metabolic alterations and an abnormal ECM may cooperatively drive cancer cell aggression and treatment resistance. Accordingly, improved methods to monitor tissue mechanics and metabolism promise to improve diagnostics and treatments to ameliorate ECM stiffening and elevated mechanosignaling may improve patient outcome. Here we discuss the interplay between ECM mechanics and metabolism in tumor biology and suggest that monitoring these processes and targeting their regulatory pathways may improve diagnostics, therapy, and the prevention of malignant transformation. PMID:25532934

  2. Antihypertensive drugs and glucose metabolism

    PubMed Central

    Rizos, Christos V; Elisaf, Moses S

    2014-01-01

    Hypertension plays a major role in the development and progression of micro- and macrovascular disease. Moreover, increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance. As a result the need for a comprehensive management of hypertensive patients is critical. However, the various antihypertensive drug categories have different effects on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis. Calcium channel blockers (CCBs) have an overall neutral effect on glucose metabolism. However, some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis. On the other hand, diuretics and β-blockers have an overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well as nebivolol seem to differentiate themselves from the rest of the β-blockers class, being more attractive options regarding their effect on glucose homeostasis. The adverse effects of some blood pressure lowering drugs on glucose metabolism may, to an extent, compromise their cardiovascular protective role. As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment, especially in patients which are at high risk for developing diabetes. PMID:25068013

  3. An overview of benzene metabolism.

    PubMed Central

    Snyder, R; Hedli, C C

    1996-01-01

    Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity. PMID:9118888

  4. Metabolic Acceleration in Human Evolution.

    PubMed

    Isler, Karin

    2016-07-12

    Humans stand out among other primates by an unusual combination of a very large brain and high fertility. Pontzer et al. (2016a) present new data on daily energy expenditure in great apes and show that the metabolic rate increased during human evolution. PMID:27411003

  5. [Bioavailability and metabolism of flavonoids].

    PubMed

    Makarova, M N

    2011-01-01

    In the review the modern data about bioavailability and a metabolism of flavonoids is considered. The data about absorption flavonoids in a digestive path, participation of microorganisms in their hydrolysis, pharmacokinetic the data on the basic classes flavonoids: flavanes (flavan-3-ols), anthocyanes, flavones, flavonols and flavanones is cited. PMID:21842747

  6. [Bioavailability and metabolism of flavonoids].

    PubMed

    Makarova, N M

    2011-01-01

    Published data about bioavailability and metabolism of flavonoids are reviewed. Information concerning the absorption of flavonoids in a digestive path and the participation of microorganisms in their hydrolysis is summarized. Parameters of pharmacokinetics are presented for the main classes of flavonoids, including flavanes (flavan-3-ols), anthocyans, flavones, flavonols, and flavanones. PMID:21870774

  7. [Motor neuron disease: metabolic evaluation].

    PubMed

    Godoy, J M; Skacel, M; Balassiano, S L; Neves, J R

    1992-03-01

    The authors studied serum and urinary calcium and phosphorus levels, as well as abnormalities on the spine of 30 patients with motor neuron disease. The authors believe in multifactorial aspects in the pathogenesis of motor neuron disease, calling special attention to toxic and metabolic factors. PMID:1307483

  8. Diurnal variations in myocardial metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasin...

  9. Glucose Metabolism in Neisseria gonorrhoeae

    PubMed Central

    Morse, Stephen A.; Stein, Stefanie; Hines, James

    1974-01-01

    The metabolism of glucose was examined in several clinical isolates of Neisseria gonorrhoeae. Radiorespirometric studies revealed that growing cells metabolized glucose by a combination on the Entner-Doudoroff and pentose phosphate pathways. A portion of the glyceraldehyde-3-phosphate formed via the Entner-Doudoroff pathway was recycled by conversion to glucose-6-phosphate. Subsequent catabolism of this glucose-6-phosphate by either the Entner-Doudoroff or pentose phosphate pathways yielded CO2 from the original C6 of glucose. Enzyme analyses confirmed the presence of all enzymes of the Entner-Doudoroff, pentose phosphate, and Embden-Meyerhof-Parnas pathways. There was always a high specific activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) relative to that of 6-phosphogluconate dehydrogenase (EC 1.1.1.44). The glucose-6-phosphate dehydrogenase utilized either nicotinamide adenine dinucleotide phosphate or nicotinamide adenine dinucleotide as electron acceptor. Acetate was the only detectable nongaseous end product of glucose metabolism. Following the disappearance of glucose, acetate was metabolized by the tricarboxylic acid cycle as evidenced by the preferential oxidation of [1-14C]acetate over that of [2-14C]acetate. When an aerobically grown log-phase culture was subjected to anaerobic conditions, lactate and acetate were formed from glucose. Radiorespirometric studies showed that under these conditions, glucose was dissimilated entirely by the Entner-Doudoroff pathway. Further studies determined that this anaerobic dissimilation of glucose was not growth dependent. PMID:4156358

  10. Substrate channeling in proline metabolism

    PubMed Central

    Arentson, Benjamin W.; Sanyal, Nikhilesh; Becker, Donald F.

    2012-01-01

    Proline metabolism is an important pathway that has relevance in several cellular functions such as redox balance, apoptosis, and cell survival. Results from different groups have indicated that substrate channeling of proline metabolic intermediates may be a critical mechanism. One intermediate is pyrroline-5-carboxylate (P5C), which upon hydrolysis opens to glutamic semialdehyde (GSA). Recent structural and kinetic evidence indicate substrate channeling of P5C/GSA occurs in the proline catabolic pathway between the proline dehydrogenase and P5C dehydrogenase active sites of bifunctional proline utilization A (PutA). Substrate channeling in PutA is proposed to facilitate the hydrolysis of P5C to GSA which is unfavorable at physiological pH. The second intermediate, gamma-glutamyl phosphate, is part of the proline biosynthetic pathway and is extremely labile. Substrate channeling of gamma-glutamyl phosphate is thought to be necessary to protect it from bulk solvent. Because of the unfavorable equilibrium of P5C/GSA and the reactivity of gamma-glutamyl phosphate, substrate channeling likely improves the efficiency of proline metabolism. Here, we outline general strategies for testing substrate channeling and review the evidence for channeling in proline metabolism. PMID:22201749

  11. Does Metabolically Healthy Obesity Exist?

    PubMed

    Muñoz-Garach, Araceli; Cornejo-Pareja, Isabel; Tinahones, Francisco J

    2016-01-01

    The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of "more fat means more metabolic disease", and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID:27258304

  12. Targeting Time in Metabolic Therapeutics.

    PubMed

    Bass, Joseph

    2016-04-12

    One of the most predictable aspects of conscious life is the daily sleep-wake cycle, which is programmed by an internal clock that exerts broad effects on behavior and physiology. Studies of He et al. (2016) identify a small molecule clock modulator that improves metabolism, revealing that enhancing circadian function benefits health. PMID:27076073

  13. Metabolic engineering in methanotrophic bacteria

    SciTech Connect

    Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. Metabolic vulnerabilities in endometrial cancer.

    PubMed

    Byrne, Frances L; Poon, Ivan K H; Modesitt, Susan C; Tomsig, Jose L; Chow, Jenny D Y; Healy, Marin E; Baker, William D; Atkins, Kristen A; Lancaster, Johnathan M; Marchion, Douglas C; Moley, Kelle H; Ravichandran, Kodi S; Slack-Davis, Jill K; Hoehn, Kyle L

    2014-10-15

    Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts. PMID:25205105

  15. HEPATOCYTE METABOLISM MODEL FOR XENOBIOTICS

    EPA Science Inventory

    • Incorporation of regulatory rules within the analysis of metabolic networks to restrict the alternative solutions and result in better estimation of internal fluxes that cannot be measured. This can be achieved utilizing logic-based programming.
    • Investi...

    • CHROMIUM, METABOLIC SYNDROME AND DIABESITY

      Technology Transfer Automated Retrieval System (TEKTRAN)

      Suboptimal intakes of the essential nutrient, chromium, are characterized by elevated blood glucose, insulin resistance, obesity, hypertriglyceridemia, and low HDL. These are also signs and symptoms of the metabolic syndrome. Improvements due to increased intake of chromium are related to the degr...

    • Photorespiratory glycolate-glyoxylate metabolism.

      PubMed

      Dellero, Younès; Jossier, Mathieu; Schmitz, Jessica; Maurino, Veronica G; Hodges, Michael

      2016-05-01

      Photorespiration is one of the major carbon metabolism pathways in oxygen-producing photosynthetic organisms. This pathway recycles 2-phosphoglycolate (2-PG), a toxic metabolite, to 3-phosphoglycerate when ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) uses oxygen instead of carbon dioxide. The photorespiratory cycle is in competition with photosynthetic CO2 fixation and it is accompanied by carbon, nitrogen and energy losses. Thus, photorespiration has become a target to improve crop yields. Moreover, during the photorespiratory cycle intermediate metabolites that are toxic to Calvin-Benson cycle and RuBisCO activities, such as 2-PG, glycolate and glyoxylate, are produced. Thus, the presence of an efficient 2-PG/glycolate/glyoxylate 'detoxification' pathway is required to ensure normal development of photosynthetic organisms. Here we review our current knowledge concerning the enzymes that carry out the glycolate-glyoxylate metabolic steps of photorespiration from glycolate production in the chloroplasts to the synthesis of glycine in the peroxisomes. We describe the properties of the proteins involved in glycolate-glyoxylate metabolism in Archaeplastida and the phenotypes observed when knocking down/out these specific photorespiratory players. Advances in our understanding of the regulation of glycolate-glyoxylate metabolism are highlighted. PMID:26994478

    • Quantification of patterns of regional cardiac metabolism

      SciTech Connect

      Lear, J.L.; Ackermann, R.F. )

      1990-09-01

      To quantitatively map and compare patterns of regional cardiac metabolism with greater spatial resolution than is possible with positron emission tomography (PET), the authors developed autoradiographic techniques for use with combinations of radiolabeled fluorodeoxyglucose (FDG), glucose (GLU), and acetate (ACE) and applied the techniques to normal rats. Kinetic models were developed to compare GLU-based oxidative glucose metabolism with FDG-based total glucose metabolism (oxidative plus anaerobic) and to compare ACE-based overall oxidative metabolism with FDG-based total glucose metabolism. GLU-based metabolism generally paralleled FDG-based metabolism, but divergence occurred in certain structures such as the papillary muscles, where FDG-based metabolism was much greater. ACE-based metabolism also generally paralleled FDG-based metabolism, but again, the papillary muscles had relatively greater FDG-based metabolism. These discrepancies between FDG-based metabolism and GLU- or ACE-based metabolism suggest the presence of high levels of anaerobic glycolysis. Thus, the study indicates that anaerobic glycolysis, in addition to occurring in ischemic or stunned myocardium (as has been shown in recent PET studies), occurs normally in specific cardiac regions, despite the presence of abundant oxygen.

    • Nutrition, Epigenetics, and Metabolic Syndrome

      PubMed Central

      Wang, Junjun; Wu, Zhenlong; Li, Defa; Li, Ning; Dindot, Scott V.; Satterfield, M. Carey; Bazer, Fuller W.

      2012-01-01

      Significance: Epidemiological and animal studies have demonstrated a close link between maternal nutrition and chronic metabolic disease in children and adults. Compelling experimental results also indicate that adverse effects of intrauterine growth restriction on offspring can be carried forward to subsequent generations through covalent modifications of DNA and core histones. Recent Advances: DNA methylation is catalyzed by S-adenosylmethionine-dependent DNA methyltransferases. Methylation, demethylation, acetylation, and deacetylation of histone proteins are performed by histone methyltransferase, histone demethylase, histone acetyltransferase, and histone deacetyltransferase, respectively. Histone activities are also influenced by phosphorylation, ubiquitination, ADP-ribosylation, sumoylation, and glycosylation. Metabolism of amino acids (glycine, histidine, methionine, and serine) and vitamins (B6, B12, and folate) plays a key role in provision of methyl donors for DNA and protein methylation. Critical Issues: Disruption of epigenetic mechanisms can result in oxidative stress, obesity, insulin resistance, diabetes, and vascular dysfunction in animals and humans. Despite a recognized role for epigenetics in fetal programming of metabolic syndrome, research on therapies is still in its infancy. Possible interventions include: 1) inhibition of DNA methylation, histone deacetylation, and microRNA expression; 2) targeting epigenetically disturbed metabolic pathways; and 3) dietary supplementation with functional amino acids, vitamins, and phytochemicals. Future Directions: Much work is needed with animal models to understand the basic mechanisms responsible for the roles of specific nutrients in fetal and neonatal programming. Such new knowledge is crucial to design effective therapeutic strategies for preventing and treating metabolic abnormalities in offspring born to mothers with a previous experience of malnutrition. Antioxid. Redox Signal. 17, 282–301. PMID

    • Dihydroxyacetone metabolism in Haloferax volcanii

      PubMed Central

      Ouellette, Matthew; Makkay, Andrea M.; Papke, R. Thane

      2013-01-01

      Dihydroxyacetone (DHA) is a ketose sugar that can be produced by oxidizing glycerol. DHA in the environment is taken up and phosphorylated to DHA-phosphate by glycerol kinase or DHA kinase. In hypersaline environments, it is hypothesized that DHA is produced as an overflow product from glycerol utilization by organisms such as Salinibacter ruber. Previous research has demonstrated that the halobacterial species Haloquadratum walsbyi can use DHA as a carbon source, and putative DHA kinase genes were hypothesized to be involved in this process. However, DHA metabolism has not been demonstrated in other halobacterial species, and the role of the DHA kinase genes was not confirmed. In this study, we examined the metabolism of DHA in Haloferax volcanii because putative DHA kinase genes were annotated in its genome, and it has an established genetic system to assay growth of mutant knockouts. Experiments in which Hfx. volcanii was grown on DHA as the sole carbon source demonstrated growth, and that it is concentration dependent. Three annotated DHA kinase genes (HVO_1544, HVO_1545, and HVO_1546), which are homologous to the putative DHA kinase genes present in Hqm. walsbyi, as well as the glycerol kinase gene (HVO_1541), were deleted to examine the effect of these genes on the growth of Hfx. volcanii on DHA. Experiments demonstrated that the DHA kinase deletion mutant exhibited diminished, but not absence of growth on DHA compared to the parent strain. Deletion of the glycerol kinase gene also reduced growth on DHA, and did so more than deletion of the DHA kinase. The results indicate that Hfx. volcanii can metabolize DHA and that DHA kinase plays a role in this metabolism. However, the glycerol kinase appears to be the primary enzyme involved in this process. BLASTp analyses demonstrate that the DHA kinase genes are patchily distributed among the Halobacteria, whereas the glycerol kinase gene is widely distributed, suggesting a widespread capability for DHA metabolism

  1. Allometric scaling laws of metabolism

    NASA Astrophysics Data System (ADS)

    da Silva, Jafferson Kamphorst Leal; Garcia, Guilherme J. M.; Barbosa, Lauro A.

    2006-12-01

    One of the most pervasive laws in biology is the allometric scaling, whereby a biological variable Y is related to the mass M of the organism by a power law, Y=YM, where b is the so-called allometric exponent. The origin of these power laws is still a matter of dispute mainly because biological laws, in general, do not follow from physical ones in a simple manner. In this work, we review the interspecific allometry of metabolic rates, where recent progress in the understanding of the interplay between geometrical, physical and biological constraints has been achieved. For many years, it was a universal belief that the basal metabolic rate (BMR) of all organisms is described by Kleiber's law (allometric exponent b=3/4). A few years ago, a theoretical basis for this law was proposed, based on a resource distribution network common to all organisms. Nevertheless, the 3/4-law has been questioned recently. First, there is an ongoing debate as to whether the empirical value of b is 3/4 or 2/3, or even nonuniversal. Second, some mathematical and conceptual errors were found these network models, weakening the proposed theoretical arguments. Another pertinent observation is that the maximal aerobically sustained metabolic rate of endotherms scales with an exponent larger than that of BMR. Here we present a critical discussion of the theoretical models proposed to explain the scaling of metabolic rates, and compare the predicted exponents with a review of the experimental literature. Our main conclusion is that although there is not a universal exponent, it should be possible to develop a unified theory for the common origin of the allometric scaling laws of metabolism.

  2. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  3. SIMULATING METABOLISM TO ENHANCE EFFECTS MODELING

    EPA Science Inventory

    A major uncertainty that has long been recognized in evaluating chemical toxicity is accounting for metabolic activation of chemicals resulting in increased toxicity. The proposed research will develop a capability for forecasting the metabolism of xenobiotic chemicals of EPA int...

  4. SFA 2.0- Metabolic Potential

    SciTech Connect

    Banfield, Jill; Beller, Harry

    2015-02-17

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

  5. The Transition from Aerobic to Anaerobic Metabolism.

    ERIC Educational Resources Information Center

    Skinner, James S.; McLellan, Thomas H.

    1980-01-01

    The transition from aerobic to anaerobic metabolism is discussed. More research is needed on different kinds of athletes and athletic activities and how they may affect aerobic and anaerobic metabolisms. (CJ)

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

    PubMed

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

    2016-02-26

    Production of energy in a cell must keep pace with demand. Photoreceptors use ATP to maintain ion gradients in darkness, whereas in light they use it to support phototransduction. Matching production with consumption can be accomplished by coupling production directly to consumption. Alternatively, production can be set by a signal that anticipates demand. In this report we investigate the hypothesis that signaling through phototransduction controls production of energy in mouse retinas. We found that respiration in mouse retinas is not coupled tightly to ATP consumption. By analyzing metabolic flux in mouse retinas, we also found that phototransduction slows metabolic flux through glycolysis and through intermediates of the citric acid cycle. We also evaluated the relative contributions of regulation of the activities of α-ketoglutarate dehydrogenase and the aspartate-glutamate carrier 1. In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines. PMID:26677218

  7. Phosphoinositide metabolism and metabolism-contraction coupling in rabbit aorta

    SciTech Connect

    Coburn, R.F.; Baron, C.; Papadopoulos, M.T. )

    1988-12-01

    The authors tested a hypothesis that metabolism-contraction coupling in vascular smooth muscle is controlled by the rate of delivery of energy to ATP-dependent reactions in the inositol phospholipid transduction system that generate second messengers exerting control on smooth muscle force. Rabbit aorta was contracted by norepinephrine (NOR) under conditions of normoxia and hypoxia, and changes in inositol phospholipid pool sizes and metabolic flux rates (J{sub F}) were determined. J{sub F} was determined by labeling free cytosolic myo-inositol by incubation of unstimulated muscle with myo-({sup 3}H)inositol and then measuring rates of incorporation of this isotope into inositol phospholipids and inositol phosphates when the muscle was activated by NOR. J{sub F} measured during maintenance of NOR-induced force was markedly inhibited during hypoxia to 40-50% of that determined during normoxia; rates of increases in inositol phosphate radioactivities were similarly depressed during NOR activation under hypoxia. The hypoxia-induced decrease in J{sub F} was associated with four- to fivefold increase in phosphatidylinositol 4-phosphate (PIP) total pool size, suggesting PIP kinase was inhibited and rate limiting. These data suggest that activation of inositol phospholipid metabolism, which generates inositol 1,4,5-trisphosphate (IP{sub 3}) and diacylglycerol, is blunted under conditions where aerobic energy production is inhibited. Data are consistent with rate-limiting effects of decreased ATP delivery, or decreased phosphate potential, on PIP kinase and reactions that control resynthesis of phosphatidylinositol.

  8. Metabolic pathway resources at MaizeGDB

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two maize metabolic networks are available at MaizeGDB: MaizeCyc (http://maizecyc.maizegdb.org, also at Gramene) and CornCyc (http://corncyc.maizegdb.org, also at the Plant Metabolic Network). MaizeCyc was developed by Gramene, and CornCyc by the Plant Metabolic Network, both in collaboration with M...

  9. Thoughts on the Teaching of Metabolism

    ERIC Educational Resources Information Center

    Metzger, Robert P.

    2006-01-01

    Systems biology, metabolomics, metabolic engineering, and other recent developments in biochemistry suggest that future biochemists will require a detailed familiarity with the compounds and pathways of intermediary metabolism and their biochemical control. The challenge to the biochemistry instructor is the presentation of metabolic pathways in a…

  10. 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 ...

  11. Opportunities for genetic improvement of metabolic diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

  12. Metabolic markers in sports medicine.

    PubMed

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

  13. Metabolic pathways of ochratoxin A.

    PubMed

    Wu, Qinghua; Dohnal, Vlastimil; Huang, Lingli; Kuča, Kamil; Wang, Xu; Chen, Guyue; Yuan, Zonghui

    2011-01-01

    Ochratoxin A (OTA) as a carcinogenic of group 2B to humans is produced by various fungi strains as Aspergillus and Penicillium. It is one of the most common contaminant in foodstuff. OTA is nephrotoxic, hepatotoxic, teratogenic, and immunotoxic and is assumed to cause Balkan Endemic Nephropathy (BEN), a chronic kidney disease in humans when it is digested in combination with mycotoxin citrinin. The metabolism affects greatly the fates and the toxicity of a mycotoxins in humans, animals, and plants. The understanding of the metabolism of mycotoxins by the organism as fungi, yeast, bacteria and enzymes would be very helpful for the control of the contamination by the mycotoxins in foods and feeds, and understanding of the biotransformation of the mycotoxin in the body of humans, animals, plants, microorganisms would be beneficial to the risk assessment of food safety. In animals and humans, OTA can be metabolized in the kidney, liver and intestines. Hydrolysis, hydroxylation, lactone-opening and conjugation are the major metabolic pathways. OTalpha (OTα) formed by the cleavage of the peptidic bond in OTA is a major metabolite not only in animals and humans, but also in microorganisms and enzyme systems. It is considered as a nontoxic product. However, the lactone-opened product (OP-OTA), found in rodents, is higher toxic than its parent, OTA.. (4R)-4-OH-OTA is the major hydroxy product in rodents, whereas the 4S isomer is the major in pigs. 10-OH-OTA is currently found only in rabbits. Furthermore, OTA can lose the chlorine on C-5 to produce ochratoxin B (OTB), and OTB is further to 4-OH-OTB and ochratoxin β (OTβ). Ochratoxin quinine/hydroquinone (OTQ/OTHQ) is the metabolite of OTA in animals. In addition, the conjugates of OTA such as hexose and pentose conjugates can be found in animals. Such more polar metabolites make OTA to eliminate faster. Currently, a debate exits on the formation of OTA-DNA adducts. Plants can metabolize OTA as well. OH-OTA methyl ester

  14. Metabolic potential of endophytic bacteria☆

    PubMed Central

    Brader, Günter; Compant, Stéphane; Mitter, Birgit; Trognitz, Friederike; Sessitsch, Angela

    2014-01-01

    The bacterial endophytic microbiome promotes plant growth and health and beneficial effects are in many cases mediated and characterized by metabolic interactions. Recent advances have been made in regard to metabolite production by plant microsymbionts showing that they may produce a range of different types of metabolites. These substances play a role in defense and competition, but may also be needed for specific interaction and communication with the plant host. Furthermore, few examples of bilateral metabolite production are known and endophytes may modulate plant metabolite synthesis as well. We have just started to understand such metabolic interactions between plants and endophytes, however, further research is needed to more efficiently make use of beneficial plant-microbe interactions and to reduce pathogen infestation as well as to reveal novel bioactive substances of commercial interest. PMID:24863894

  15. Asparagine Metabolic Pathways in Arabidopsis.

    PubMed

    Gaufichon, Laure; Rothstein, Steven J; Suzuki, Akira

    2016-04-01

    Inorganic nitrogen in the form of ammonium is assimilated into asparagine via multiple steps involving glutamine synthetase (GS), glutamate synthase (GOGAT), aspartate aminotransferase (AspAT) and asparagine synthetase (AS) in Arabidopsis. The asparagine amide group is liberated by the reaction catalyzed by asparaginase (ASPG) and also the amino group of asparagine is released by asparagine aminotransferase (AsnAT) for use in the biosynthesis of amino acids. Asparagine plays a primary role in nitrogen recycling, storage and transport in developing and germinating seeds, as well as in vegetative and senescence organs. A small multigene family encodes isoenzymes of each step of asparagine metabolism in Arabidopsis, except for asparagine aminotransferase encoded by a single gene. The aim of this study is to highlight the structure of the genes and encoded enzyme proteins involved in asparagine metabolic pathways; the regulation and role of different isogenes; and kinetic and physiological properties of encoded enzymes in different tissues and developmental stages. PMID:26628609

  16. Metabolic Engineering of Saccharomyces cerevisiae

    PubMed Central

    Ostergaard, Simon; Olsson, Lisbeth; Nielsen, Jens

    2000-01-01

    Comprehensive knowledge regarding Saccharomyces cerevisiae has accumulated over time, and today S. cerevisiae serves as a widley used biotechnological production organism as well as a eukaryotic model system. The high transformation efficiency, in addition to the availability of the complete yeast genome sequence, has facilitated genetic manipulation of this microorganism, and new approaches are constantly being taken to metabolicially engineer this organism in order to suit specific needs. In this paper, strategies and concepts for metabolic engineering are discussed and several examples based upon selected studies involving S. cerevisiae are reviewed. The many different studies of metabolic engineering using this organism illustrate all the categories of this multidisciplinary field: extension of substrate range, improvements of producitivity and yield, elimination of byproduct formation, improvement of process performance, improvements of cellular properties, and extension of product range including heterologous protein production. PMID:10704473

  17. Peroxisome Metabolism and Cellular Aging

    PubMed Central

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  18. Spontaneous emergence of a metabolism

    SciTech Connect

    Bagley, R.J.; Farmer, J.D. Santa Fe Inst., NM )

    1990-01-01

    Networks of catalyzed reactions with nonlinear feedback have been proposed to play an important role in the origin of life. We investigate this possibility in a polymer chemistry with catalyzed cleavage and condensation reactions. We study the properties of a well-stirred reactor driven away from equilibrium by the flow of mass. Under appropriate non-equilibrium conditions. The nonlinear feedback of the reaction network focuses the material of the system into a few specific polymer species. The network of catalytic reactions digests'' the material of its environment, incorporating it into its own form. We call the result an autocatalytic metabolism. Under some variations it persists almost unchanged, while in other cases it dies. We argue that the dynamical stability of autocatalytic metabolisms gives them regenerative properties that allow them to repair themselves and to propagate through time. 43 refs., 16 figs., 3 tabs.

  19. Toward Engineering Synthetic Microbial Metabolism

    PubMed Central

    McArthur, George H.; Fong, Stephen S.

    2010-01-01

    The generation of well-characterized parts and the formulation of biological design principles in synthetic biology are laying the foundation for more complex and advanced microbial metabolic engineering. Improvements in de novo DNA synthesis and codon-optimization alone are already contributing to the manufacturing of pathway enzymes with improved or novel function. Further development of analytical and computer-aided design tools should accelerate the forward engineering of precisely regulated synthetic pathways by providing a standard framework for the predictable design of biological systems from well-characterized parts. In this review we discuss the current state of synthetic biology within a four-stage framework (design, modeling, synthesis, analysis) and highlight areas requiring further advancement to facilitate true engineering of synthetic microbial metabolism. PMID:20037734

  20. Mast cells and metabolic syndrome

    PubMed Central

    Zhang, Jie; Shi, Guo-Ping

    2011-01-01

    Mast cells are critical effectors in the development of allergic diseases and in many immunoglobulin E–mediated immune responses. These cells exert their physiological and pathological activities by releasing granules containing histamine, cytokines, chemokines, and proteases, including mast cell-specific chymase and tryptase. Like macrophages and T lymphocytes, mast cells are inflammatory cells, and they participate in the pathogenesis of inflammatory diseases such as cardiovascular complications and metabolic disorders. Recent observations suggested that mast cells are involved in insulin resistance and type 2 diabetes. Data from animal models proved the direct participation of mast cells in diet-induced obesity and diabetes. Although the mechanisms by which mast cells participate in these metabolic diseases are not fully understood, established mast cell pathobiology in cardiovascular diseases and effective mast cell inhibitor medications used in pre-formed obesity and diabetes in experimental models offer hope to patients with these common chronic inflammatory diseases. PMID:21185370

  1. [Metabolic rhabdomyolysis during statin therapy].

    PubMed

    Vergely, N; Leca, V; Antoine, J-C; Germain, N; Khalfallah, Y; Estour, B

    2009-08-01

    The occurrence of rhabdomyolysis during statin treatment for dyslipidemia is a well-known side effect. However, the differential diagnosis of rhabdomyolysis is large. We report on a patient treated with statin who presented a rhabdomyolysis. The persistence of laboratory abnormalities allowed to discover a metabolic rhabdomyolysis, namely a carnitine palmitoyltransférase II deficiency. The diagnosis of the genetic abnormality allows to modify the therapeutic care. PMID:19419805

  2. NAD metabolism in Vibrio cholerae.

    PubMed Central

    Foster, J W; Brestel, C

    1982-01-01

    Extracts of Vibrio cholerae were assayed for various enzymatic activities associated with pyridine nucleotide cycle metabolism. The activities measured include NAD glycohydrolase, nicotinamide deamidase, nicotinamide mononucleotide deamidase, and nicotinic acid phosphoribosyltransferase. The results obtained demonstrate the existence in V. cholerae of the five-membered pyridine nucleotide cycle and the potential for a four-membered pyridine nucleotide cycle. The data presented also suggest that most of the NAD glycohydrolase in V. cholerae extracts is not directly related to cholera toxin. PMID:6119307

  3. Glucagon Metabolism in the Rat

    PubMed Central

    Emmanouel, D. S.; Jaspan, J. B.; Rubenstein, A. H.; Huen, A. H-J.; Fink, E.; Katz, A. I.

    1978-01-01

    The renal handling of the biologically active glucagon component (the 3,500-mol wt fraction of immunoreactive glucagon [IRG]) and the contribution of the kidney to its overall peripheral metabolism were studied in normal and uremic rats. The metabolic clearance rate of glucagon was 31.8 ± 1.2 ml/min per kg in normal animals and was diminished by approximately one-third in each of three groups of rats with compromized renal function: 22.3±1.6 ml/min per kg in partially (70%) nephrectomized; 22.9±3.3 ml/min per kg in bilaterally ureteral ligated; and 23.2±1.2 ml/min per kg in bilaterally nephrectomized animals. In normal rats the kidney contributed 30% to the overall metabolic clearance of the hormone and the renal extraction of endogenous and exogenous glucagon was similar, averaging 22.9±1.6% and was independent of plasma IRG levels over a wide range of arterial concentrations. The remnant kidney of partially (70%) nephrectomized animals continued to extract substantial amounts (16.6±4.2%) of the hormone, but accounted for only 8% of the total peripheral catabolism of IRG. In the two groups of animals with filtering kidneys, renal glucagon uptake was linearly related to its filtered load and could be accounted for by glomerular filtration and tubular reabsorption. However, the kidneys of animals with both ureters ligated (renal extraction of inulin = 3.2±1.8%) and hence virtual absence of glomerular filtration, continued to extract 11.5±1.9% of the renal arterial glucagon, contributing by 9% to its overall metabolic clearance, indicating that IRG uptake occurs also from the post glomerular capillaries. PMID:659638

  4. Bile acids as metabolic regulators

    PubMed Central

    Li, Tiangang; Chiang, John Y. L.

    2015-01-01

    Summary Small molecule ligands that target to TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut-liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type-2 diabetes. PMID:25584736

  5. Carbohydrate metabolism of malarial parasites

    PubMed Central

    Homewood, C. A.

    1977-01-01

    The evidence for the pathways involved in the metabolism of carbohydrates by malarial parasites is critically reviewed. In all species studied, glucose is catabolized mainly by glycolysis with little participation of the pentose—phosphate pathway. It has not been proved conclusively that there is a functioning citric acid cycle in the intraerythrocytic stages of avian plasmodia, nor is it certain that these stages of any malarial parasites use oxygen. PMID:338181

  6. Renal Ammonia Metabolism and Transport

    PubMed Central

    Weiner, I. David; Verlander, Jill W.

    2015-01-01

    Renal ammonia metabolism and transport mediates a central role in acid-base homeostasis. In contrast to most renal solutes, the majority of renal ammonia excretion derives from intrarenal production, not from glomerular filtration. Renal ammoniagenesis predominantly results from glutamine metabolism, which produces 2 NH4+ and 2 HCO3− for each glutamine metabolized. The proximal tubule is the primary site for ammoniagenesis, but there is evidence for ammoniagenesis by most renal epithelial cells. Ammonia produced in the kidney is either excreted into the urine or returned to the systemic circulation through the renal veins. Ammonia excreted in the urine promotes acid excretion; ammonia returned to the systemic circulation is metabolized in the liver in a HCO3−-consuming process, resulting in no net benefit to acid-base homeostasis. Highly regulated ammonia transport by renal epithelial cells determines the proportion of ammonia excreted in the urine versus returned to the systemic circulation. The traditional paradigm of ammonia transport involving passive NH3 diffusion, protonation in the lumen and NH4+ trapping due to an inability to cross plasma membranes is being replaced by the recognition of limited plasma membrane NH3 permeability in combination with the presence of specific NH3-transporting and NH4+-transporting proteins in specific renal epithelial cells. Ammonia production and transport are regulated by a variety of factors, including extracellular pH and K+, and by several hormones, such as mineralocorticoids, glucocorticoids and angiotensin II. This coordinated process of regulated ammonia production and transport is critical for the effective maintenance of acid-base homeostasis. PMID:23720285

  7. Epinephrine and the metabolic syndrome.

    PubMed

    Ziegler, Michael G; Elayan, Hamzeh; Milic, Milos; Sun, Ping; Gharaibeh, Munir

    2012-02-01

    Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome. PMID:22124970

  8. Mitochondrial Metabolism in Aging Heart.

    PubMed

    Lesnefsky, Edward J; Chen, Qun; Hoppel, Charles L

    2016-05-13

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  9. Sirtuins Link Inflammation and Metabolism

    PubMed Central

    Vachharajani, Vidula T.; Liu, Tiefu; Wang, Xianfeng; Hoth, Jason J.; Yoza, Barbara K.; McCall, Charles E.

    2016-01-01

    Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1–7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to “defend and mend” against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to “defend” against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to “mend,” leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis. PMID:26904696

  10. Metabolic aspects of bacterial persisters

    PubMed Central

    Prax, Marcel; Bertram, Ralph

    2014-01-01

    Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by 13C-isotopolog profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds. PMID:25374846

  11. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  12. Synthetic metabolons for metabolic engineering.

    PubMed

    Singleton, Chloe; Howard, Thomas P; Smirnoff, Nicholas

    2014-05-01

    It has been proposed that enzymes can associate into complexes (metabolons) that increase the efficiency of metabolic pathways by channelling substrates between enzymes. Metabolons may increase flux by increasing the local concentration of intermediates, decreasing the concentration of enzymes needed to maintain a given flux, directing the products of a pathway to a specific subcellular location or minimizing the escape of reactive intermediates. Metabolons can be formed by relatively loose non-covalent protein-protein interaction, anchorage to membranes, and (in bacteria) by encapsulation of enzymes in protein-coated microcompartments. Evidence that non-coated metabolons are effective at channelling substrates is scarce and difficult to obtain. In plants there is strong evidence that small proportions of glycolytic enzymes are associated with the outside of mitochondria and are effective in substrate channelling. More recently, synthetic metabolons, in which enzymes are scaffolded to synthetic proteins or nucleic acids, have been expressed in microorganisms and these provide evidence that scaffolded enzymes are more effective than free enzymes for metabolic engineering. This provides experimental evidence that metabolons may have a general advantage and opens the way to improving the outcome of metabolic engineering in plants by including synthetic metabolons in the toolbox. PMID:24591054

  13. Genetic determinants of HDL metabolism.

    PubMed

    Ossoli, A; Gomaraschi, M; Franceschini, G; Calabresi, L

    2014-01-01

    Plasma high density lipoproteins (HDL) comprise a highly heterogeneous family of lipoprotein particles, with subclasses that can be separated and identified according to density, size, surface charge as well as shape and protein composition. There is evidence that these subclasses may differ in their functional properties. The individual plasma HDL cholesterol (HDL-C) level is generally taken as a snapshot of the steady-state concentration of all circulating HDL subclasses together, but this is insufficient to capture the structural and functional variation in HDL particles. HDL are continuously remodeled and metabolized in plasma and interstitial fluids, through the interaction with a large number of factors, including structural proteins, membrane transporters, enzymes, transfer proteins and receptors. Genetic variation in these factors can lead to essential changes in plasma HDL levels, and to remarkable changes in HDL particle density, size, surface charge, shape, and composition in lipids and apolipoproteins. This review discusses the impact of rare mutations and common variants in genes encoding factors involved in HDL remodeling and metabolism on plasma HDL-C levels and particle distribution. The study of the effects of human genetic variation in major players in HDL metabolism provides important clues on how individual factors modulate the formation, maturation, remodeling and catabolism of HDL. PMID:24606513

  14. Bisphenol A: Targeting metabolic tissues.

    PubMed

    Chevalier, Nicolas; Fénichel, Patrick

    2015-12-01

    The prevalence of obesity, metabolic syndrome and type 2 diabetes has dramatically increased worldwide over the last few decades. Although genetic predisposition and lifestyle factors like decreased physical activity and energy-dense diet are well-known factors in the pathophysiology of these conditions, accumulating evidence suggests that the increase in endocrine disrupting chemicals (EDCs) in the environment also explains a substantial part of the incidence of these metabolic diseases. Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. Most people are exposed to it daily by consuming food and beverages into which BPA has leached from polycarbonate containers, including reusable bottles and baby bottles. Although initially considered to be a weak environmental estrogen, BPA may be similar in potency to 17β-estradiol in stimulating cellular responses, especially at low but environmentally relevant doses (nM), as more recent studies have demonstrated. In this review, we summarize both epidemiological evidence and in vivo experimental data that point to an association between BPA exposure and the induction of insulin resistance and/or disruption of pancreatic beta cell function and/or obesity. We then discuss the in vitro data and explain the potential mechanisms involved in the metabolic disorders observed after BPA exposure. PMID:26820262

  15. Identification of Metabolic Pathway Systems

    PubMed Central

    Dolatshahi, Sepideh; Voit, Eberhard O.

    2016-01-01

    The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE) was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems. PMID:26904095

  16. Sirtuins Link Inflammation and Metabolism.

    PubMed

    Vachharajani, Vidula T; Liu, Tiefu; Wang, Xianfeng; Hoth, Jason J; Yoza, Barbara K; McCall, Charles E

    2016-01-01

    Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1-7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to "defend and mend" against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to "defend" against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to "mend," leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis. PMID:26904696

  17. Bone Metabolism after Bariatric Surgery

    PubMed Central

    Yu, Elaine W.

    2014-01-01

    Bariatric surgery is a popular and effective treatment for severe obesity, but may have negative effects on the skeleton. This review summarizes changes in bone density and bone metabolism from animal and clinical studies of bariatric surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts from obesity and weight loss are also considered. Despite challenges in bone density imaging, the preponderance of evidence suggests that bariatric surgery procedures have negative skeletal effects that persist beyond the first year of surgery, and that these effects vary by surgical type. The long-term clinical implications and current clinical recommendations are presented. Further study is required to determine mechanisms of bone loss after bariatric surgery. Although early studies focused on calcium/vitamin D metabolism and mechanical unloading of the skeleton, it seems likely that surgically-induced changes in the hormonal and metabolic profile may be responsible for the skeletal phenotypes observed after bariatric surgery. PMID:24677277

  18. 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

  19. Metabolic Syndrome and the Lung.

    PubMed

    Baffi, Cynthia W; Wood, Lisa; Winnica, Daniel; Strollo, Patrick J; Gladwin, Mark T; Que, Loretta G; Holguin, Fernando

    2016-06-01

    A link between metabolic syndrome (MetS) and lung diseases has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms, greater lung function impairment, pulmonary hypertension, and asthma. This review will discuss several potential mechanisms to explain these associations, including dietary factors and the effect of adiposity and fat-induced inflammation on the lungs, and the role of other comorbidities that frequently coexist with MetS, such as OSA and obesity. In contrast to the well-known association between asthma and obesity, the recognition that MetS affects the lung is relatively new. Although some controversy remains as to whether MetS is a unique disease entity, its individual components have independently been associated with changes in pulmonary function or lung disease. There is, however, uncertainty as to the relative contribution that each metabolic factor has in adversely affecting the respiratory system; also, it is unclear how much of the MetS-related lung effects occur independently of obesity. In spite of these epidemiological limitations, the proposed mechanistic pathways strongly suggest that this association is likely to be causal. Given the wide prevalence of MetS in the general population, it is imperative that we continue to further understand how this metabolic disorder impacts the lung and how to prevent its complications. PMID:26836925

  20. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.

  1. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    PubMed

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  2. Genome-scale modeling for metabolic engineering

    SciTech Connect

    Simeonidis, E; Price, ND

    2015-01-13

    We focus on the application of constraint-based methodologies and, more specifically, flux balance analysis in the field of metabolic engineering, and enumerate recent developments and successes of the field. We also review computational frameworks that have been developed with the express purpose of automatically selecting optimal gene deletions for achieving improved production of a chemical of interest. The application of flux balance analysis methods in rational metabolic engineering requires a metabolic network reconstruction and a corresponding in silico metabolic model for the microorganism in question. For this reason, we additionally present a brief overview of automated reconstruction techniques. Finally, we emphasize the importance of integrating metabolic networks with regulatory information-an area which we expect will become increasingly important for metabolic engineering-and present recent developments in the field of metabolic and regulatory integration.

  3. Nuclear receptors in bile acid metabolism

    PubMed Central

    Li, Tiangang; Chiang, John Y. L.

    2013-01-01

    Bile acids are signaling molecules that activate nuclear receptors, such as farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, and vitamin D receptor, and play a critical role in the regulation of lipid, glucose, energy, and drug metabolism. These xenobiotic/endobiotic-sensing nuclear receptors regulate phase I oxidation, phase II conjugation, and phase III transport in bile acid and drug metabolism in the digestive system. Integration of bile acid metabolism with drug metabolism controls absorption, transport, and metabolism of nutrients and drugs to maintain metabolic homeostasis and also protects against liver injury, inflammation, and related metabolic diseases, such as nonalcoholic fatty liver disease, diabetes, and obesity. Bile-acid–based drugs targeting nuclear receptors are in clinical trials for treating cholestatic liver diseases and fatty liver disease. PMID:23330546

  4. Interplay between oxidant species and energy metabolism.

    PubMed

    Quijano, Celia; Trujillo, Madia; Castro, Laura; Trostchansky, Andrés

    2016-08-01

    It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases. PMID:26741399

  5. Metabolic consequences of sleep and circadian disorders

    PubMed Central

    Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

  6. Metabolism and the Circadian Clock Converge

    PubMed Central

    Eckel-Mahan, Kristin

    2013-01-01

    Circadian rhythms occur in almost all species and control vital aspects of our physiology, from sleeping and waking to neurotransmitter secretion and cellular metabolism. Epidemiological studies from recent decades have supported a unique role for circadian rhythm in metabolism. As evidenced by individuals working night or rotating shifts, but also by rodent models of circadian arrhythmia, disruption of the circadian cycle is strongly associated with metabolic imbalance. Some genetically engineered mouse models of circadian rhythmicity are obese and show hallmark signs of the metabolic syndrome. Whether these phenotypes are due to the loss of distinct circadian clock genes within a specific tissue versus the disruption of rhythmic physiological activities (such as eating and sleeping) remains a cynosure within the fields of chronobiology and metabolism. Becoming more apparent is that from metabolites to transcription factors, the circadian clock interfaces with metabolism in numerous ways that are essential for maintaining metabolic homeostasis. PMID:23303907

  7. Interplay between oxidant species and energy metabolism

    PubMed Central

    Quijano, Celia; Trujillo, Madia; Castro, Laura; Trostchansky, Andrés

    2015-01-01

    It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases. PMID:26741399

  8. Metabolism, variability and risk assessment.

    PubMed

    Dorne, J L C M

    2010-02-01

    For non-genotoxic carcinogens, "thresholded toxicants", Acceptable/Tolerable Daily Intakes (ADI/TDI) represent a level of exposure "without appreciable health risk" when consumed everyday or weekly for a lifetime and are derived by applying an uncertainty factor of a 100-fold to a no-observed-adverse-effect-levels (NOAEL) or to a benchmark dose. This UF allows for interspecies differences and human variability and has been subdivided to take into account toxicokinetics and toxicodynamics with even values of 10(0.5) (3.16) for the human aspect. Ultimately, such refinements allow for chemical-specific adjustment factors and physiologically based models to replace such uncertainty factors. Intermediate to chemical-specific adjustment factors are pathway-related uncertainty factors which have been derived for phase I, phase II metabolism and renal excretion. Pathway-related uncertainty factors are presented here as derived from the result of meta-analyses of toxicokinetic variability data in humans using therapeutic drugs metabolised by a single pathway in subgroups of the population. Pathway-related lognormal variability was derived for each metabolic route. The resulting pathway-related uncertainty factors showed that the current uncertainty factor for toxicokinetics (3.16) would not cover human variability for genetic polymorphism and age differences (neonates, children, the elderly). Latin hypercube (Monte Carlo) models have also been developed using quantitative metabolism data and pathway-related lognormal variability to predict toxicokinetics variability and uncertainty factors for compounds handled by several metabolic routes. For each compound, model results gave accurate predictions compared to published data and observed differences arose from data limitations, inconsistencies between published studies and assumptions during model design and sampling. Finally, under the 6(th) framework EU project NOMIRACLE (http://viso.jrc.it/nomiracle/), novel methods to

  9. Industry as a metabolic activity.

    PubMed

    Smart, B

    1992-02-01

    The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to

  10. Metabolism

    MedlinePlus

    ... digestive system called enzymes break proteins down into amino acids, fats into fatty acids, and carbohydrates into simple ... for example, glucose). In addition to sugar, both amino acids and fatty acids can be used as energy ...

  11. Metabolism

    MedlinePlus

    ... digestive system called enzymes break proteins down into amino acids, fats into fatty acids, and carbohydrates into simple ... e.g., glucose). In addition to sugar, both amino acids and fatty acids can be used as energy ...

  12. Metabolism

    MedlinePlus

    ... convert or use energy, such as: Breathing Circulating blood Controlling body temperature Contracting muscles Digesting food and nutrients Eliminating waste through urine and feces Functioning of the brain and nerves

  13. Challenges in diagnosing a metabolic disorder: error of pyruvate metabolism or drug induced?

    PubMed

    Mampilly, George Tomy; Mampilly, Tomy Kochuvareed; Christopher, Rita; Chandramohan, Neeradha; Janaki, Vijayalakshmy

    2014-06-01

    Certain drugs are known to cause metabolic changes resulting in altered metabolic profiles. We report here a case where a combination of antiepileptic drugs resulted in a profile that mimicked a metabolic disorder. A 16month-old female child on antiepileptic drugs (valproate and topiramate) was suspected to have the inherited metabolic disorder, dihydrolipoamide dehydrogenase deficiency, based on clinical symptoms and metabolic profile showing hyperalaninemia, elevated branched-chain amino acids, and lactate-pyruvate ratio. Suspecting that the observed metabolic changes could have also arised from medication, current medication was weaned off and replaced with levetiracetam, clonazepam, and levocarnitine (supportive therapy). Metabolic profiling conducted after 47 days showed normal alanine, branched-chain amino acids, ornithine, and lactate-pyruvate ratio, suggesting that the earlier abnormalities could have been medication induced. We stress that metabolic changes resulting from chronic medication should be considered while interpreting a positive result when investigating an inherited metabolic disorder. PMID:23439713

  14. Metabolic fingerprint of dimethyl sulfone (DMSO2) in microbial-mammalian co-metabolism.

    PubMed

    He, Xuan; Slupsky, Carolyn M

    2014-12-01

    There is growing awareness that intestinal microbiota alters the energy harvesting capacity of the host and regulates metabolism. It has been postulated that intestinal microbiota are able to degrade unabsorbed dietary components and transform xenobiotic compounds. The resulting microbial metabolites derived from the gastrointestinal tract can potentially enter the circulation system, which, in turn, affects host metabolism. Yet, the metabolic capacity of intestinal microbiota and its interaction with mammalian metabolism remains largely unexplored. Here, we review a metabolic pathway that integrates the microbial catabolism of methionine with mammalian metabolism of methanethiol (MT), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), which together provide evidence that supports the microbial origin of dimethyl sulfone (DMSO2) in the human metabolome. Understanding the pathway of DMSO2 co-metabolism expends our knowledge of microbial-derived metabolites and motivates future metabolomics-based studies on ascertaining the metabolic consequences of intestinal microbiota on human health, including detoxification processes and sulfur xenobiotic metabolism. PMID:25245235

  15. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies

    SciTech Connect

    O'Grady, J; Schwender, J; Shachar-Hill, Y; Morgan, JA

    2012-03-26

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (CO2)-C-13 dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  16. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies

    SciTech Connect

    O'Grady J.; Schwender J.; Shachar-Hill, Y.; Morgan, J. A.

    2012-03-01

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on {sup 13}CO{sub 2} dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  17. Interaction between vitamin B6 metabolism, nitrogen metabolism and autoimmunity.

    PubMed

    Colinas, Maite; Fitzpatrick, Teresa B

    2016-04-01

    The essential micronutrient vitamin B6 is best known in its enzymatic cofactor form, pyridoxal 5'-phosphate (PLP). However, vitamin B6 comprises the amine pyridoxamine 5'-phosphate (PMP) and the alcohol pyridoxine 5'-phosphate (PNP) in addition to PLP, as well as their corresponding non-phosphorylated forms. The different B6 forms (called vitamers) are enzymatically interconverted in a ubiquitous salvage pathway. Recently, we have shown that balancing the ratio of the different B6 vitamers in particular PMP by the PMP/PNP oxidase PDX3 is essential for growth and development in Arabidopsis thaliana. Intriguingly, nitrate to ammonium conversion is impaired in pdx3 mutants, such that the mutants become ammonium-dependent, suggesting an interaction between vitamin B6 and nitrogen metabolism. In addition, we found a strong up-regulation of genes related to plant defense. Here, we further show that pdx3 mutants display a temperature-sensitive phenotype that is typical of autoimmune mutants and is possibly connected to the impaired nitrogen metabolism. PMID:27018849

  18. Metabolic cost of rope training.

    PubMed

    Fountaine, Charles J; Schmidt, Brad J

    2015-04-01

    Rope training, consisting of vigorously undulating a rope with the upper body, has become a popular cardiovascular training choice in fitness centers and athletic performance enhancement facilities. Despite widespread use and growing popularity, little is known about the metabolic demands of rope training. Therefore, the purpose of this study was to quantify the cardiovascular and metabolic cost from an acute 10-minute bout of rope training. Eleven physically active participants used a 15.2-m rope anchored by a post, resulting in the participant holding 7.6 m of rope in each hand. The 10-minute protocol consisted of 15 seconds of vertical double-arm waves followed by 45 seconds of rest for 10 total repetitions. The metabolic cost was estimated from heart rate, lactate, resting O2 uptake, exercise O2 uptake, and excess postexercise O2 consumption measurements. The average heart rate for the workout was 163 ± 11 b·min with peak (Equation is included in full-text article.) of 35.4 ± 5.4 mL·kg(-1)·min(-1), and peak METs were 10.1 ± 1.6. Total energy expenditure was 467.3 ± 161.0 kJ. When expressed per unit of time, EE was 41.3 ± 14.1 kJ·min(-1). The results of this study suggest an acute 10-minute bout of rope training in a vigorous-intensity workout, resulting in high heart rates and energy expenditure, which meet previously established thresholds known to increase cardiorespiratory fitness. PMID:23897017

  19. Phase II metabolism of benzene.

    PubMed Central

    Schrenk, D; Orzechowski, A; Schwarz, L R; Snyder, R; Burchell, B; Ingelman-Sundberg, M; Bock, K W

    1996-01-01

    The hepatic metabolism of benzene is thought to be a prerequisite for its bony marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase II metabolites such as PH sulfate and PH glucuronide. Pretreatment of animals with 3-methylcholantrene (3-MC) markedly increased PH glucuronide formation while PH sulfate formation was decreased. Likewise, V79 cells transfected with the 3-MC-inducible rat UGT1.6 cDNA showed a considerable rate of PH and HQ glucuronidation. In addition to inducing glucuronidation of phenols, 3-MC treatment (reported to protect rats from the myelotoxicity of benzene) resulted in a decrease of hepatic CYP2E1. In contrast, pretreatment of rats with the CYP2E1-inducer isopropanol strongly enhanced benzene metabolism and the formation of phenolic metabolites. Mouse hepatocytes formed much higher amounts of HQ than rat hepatocytes and considerable amounts of 1,2,4-trihydroxybenzene (THB) sulfate and HQ sulfate. In conclusion, the protective effect of 3-MC in rats is probably due to a shift from the labile PH sulfate to the more stable PH glucuronide, and to a decrease in hepatic CYP2E1. The higher susceptibility of mice toward benzene may be related to the high rate of formation of the myelotoxic metabolite HQ and the semistable phase II metabolites HQ sulfate and THB sulfate. Images Figure 4. PMID:9118891

  20. Inflammation and sex hormone metabolism.

    PubMed

    Schmidt, Martin; Naumann, Heidrun; Weidler, Claudia; Schellenberg, Martina; Anders, Sven; Straub, Rainer H

    2006-06-01

    The incidence of autoimmune diseases is higher in females than in males. In both sexes, adrenal hormones, that is, glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are inadequately low in patients when compared to healthy controls. Hormonally active androgens are anti-inflammatory, whereas estrogens are pro-inflammatory. Therefore, the mechanisms responsible for the alterations of steroid profiles in inflammation are of major interest. The local metabolism of androgens and estrogens may determine whether a given steroid profile found in a subject's blood results in suppression or promotion of inflammation. The steroid metabolism in mixed synovial cells, fibroblasts, macrophages, and monocytes was assessed. Major focus was on cells from patients with rheumatoid arthritis (RA), while cells from patients with osteoarthritis served as controls. Enzymes directly or indirectly involved in local sex steroid metabolism in RA are: DHEA-sulfatase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and aromatase (CYP19), which are required for the synthesis of sex steroids from precursors, 5alpha-reductase and 16alpha-hydroxylase, which can be involved either in the generation of more active steroids or in the pathways leading to depletion of active hormones, and 3alpha-reductase and 7alpha-hydroxylase (CYP7B), which unidirectionally are involved in the depletion of active hormones. Androgens inhibit aromatization in synovial cells when their concentration is sufficiently high. As large amounts of estrogens are formed in synovial tissue, there may be a relative lack of androgens. Production of 5alpha-reduced androgens should increase the local anti-inflammatory activity; however, it also opens a pathway for the inactivation of androgens. The data discussed here suggest that therapy of RA patients may benefit from the use of nonaromatizable androgens and/or the use of aromatase inhibitors. PMID:16855150

  1. Anaerobic metabolism in Brassica seedlings

    NASA Astrophysics Data System (ADS)

    Park, Myoung-Ryoul; Hasenstein, Karl H.

    Germination typically depends on oxidative respiration. The lack of convection under space conditions may create hypoxic or conditions during seed germination. We investigated the effect of reduced oxygen on seed germination and metabolism to understand how metabolic constraints affect seed growth and responsiveness to reorientation. Germination was completely inhibited when seeds were imbibed in the absence of oxygen; germination occurred at 5% oxygen and higher levels. Adding oxygen after 72 h resulted in immediate germination (protrusion of the radicle). Hypoxia typically activates alcohol dehydrogenase (ADH, EC 1.1.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) which produce ethanol and/or L-lactate, respectively. We report on the expression of ADH1 and LDH1, and changes in total soluble sugars, starch, pH, and L-lactate in seedlings grown at 28°C in 0, 2.5, 5, 10% and ambient (21%) oxygen conditions as controls. The highest consumption (lowest level) of sugars was seen at 0% oxygen but the lowest level of starch occurred 24 h after imbibition under ambient condition. Expression levels of ADH1 in ambient oxygen condition increased within 24 h but increased threefold under hypoxic conditions; LDH1 increased up to 8-fold under hypoxia compared to controls but ADH1 and LDH1 were less expressed as the oxygen levels increased. The intracellular pH of seeds decreased as the content of L-lactate increased for all oxygen concentrations. These results indicate that germination of Brassica is sensitive to oxygen levels and that oxygen availability during germination is an important factor for metabolic activities. (Supported by NASA grant NNX10AP91G)

  2. Dyslipidemic drugs in metabolic syndrome

    PubMed Central

    Siddiqi, Sheelu S.; Misbahuddin; Ahmad, Farida; Rahman, Syed Z.; Khan, Asad U.

    2013-01-01

    Introduction: Metabolic syndrome predisposes to diabetes and atherosclerotic vascular disease. Statins reduce cardiovascular events, so all metabolic syndrome patients should be evaluated for dyslipidemia. Many patients fail to achieve lipid goals with statin monotherapy. Co-administration of ezetimibe (EZE) and atorvastatin (ATV) may enable more patients to achievelow-density lipoproteincholesterol (LDL-C) goal while avoiding risks of high-dose statin monotherapy. Materials and Methods: The present study compares rosuvastatin (Rsv) with a combination of (Atv) and (Eze). Metabolic syndrome patients, 30-70 years with LDL-C ≥130 mg/dl and a 10-year CHD risk score of 10% were randomized to double-blind treatment with (Rsv) 5 mg (n = 67) or (Atv) 10 mg+(Eze) 10 mg (n = 68) for 12 weeks. Results: LDL-C reduced significantly; (32.3% and 30.3%, P < 0.001) in (Atv)+(Eze) and (Rsv), respectively, but there was no significant difference between two arms. More patients achieved LDL-C goal of ≤100 mg/dl with (Atv)+(Eze) compared to (Rsv) (65% vs. 58%, P < 0.05). Triglycerides (TG) were reduced more with (Atv)+(Eze) compared to (Rsv) (28.1% and 21.4%, P < 0.001). Greater increase in high-density lipoprotein cholesterol (HDL-C) was observed with (Atv)+(Eze). Both treatments were well tolerated. Conclusion: This study shows that the combination of (Atv)+(Eze) has more efficacy and comparable safety to that of (Rsv). PMID:23869305

  3. Estrogen Metabolism and Breast Cancer

    PubMed Central

    Samavat, Hamed; Kurzer, Mindy S

    2015-01-01

    There is currently accumulating evidence that endogenous estrogens play a critical role in the development of breast cancer. Estrogens and their metabolites have been studied in both pre- and postmenopausal women with more consistent results shown in the latter population, in part because of large hormonal variations during the menstrual cycle and far fewer studies having been performed in premenopausal women. In this review we describe in detail estrogen metabolism and associated genetic variations, and provide a critical review of the current literature regarding the role of estrogens and their metabolites in breast cancer risk. PMID:24784887

  4. Thiophene metabolism by E. coli

    SciTech Connect

    Clark, D.P.

    1990-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur containing heterocyclic molecules by mutants of Escherichia coli K-12. We previously isolated multiple mutants of E. coli which were selected for improved oxidation of furan and thiophene derivatives. We have focused on the thdA mutation in our subsequent research as it appears to be of central importance in thiophene oxidation. We hope that analysis of the thd gene of E. coli will lead to improvement of our thiophene metabolizing bacterial strains.

  5. Metabolic effects of contraceptive steroids.

    PubMed

    Sitruk-Ware, Regine; Nath, Anita

    2011-06-01

    Estrogen and progestins have been used by millions of women as effective combined contraceptives. The safety of hormonal contraceptives has been documented by years of follow-up and serious adverse events that may be related to their use are rare in the young population exposed to these agents. The balance between the benefits and the risks of contraceptive steroids is generally positive in particular when comparing to the risks of pregnancy and especially in women with risk factors. The metabolic changes induced by the synthetic steroids used in contraception, such as lipoprotein changes, insulin response to glucose, and coagulation factors have been considered as potential markers of cardiovascular and venous risk. Observations of these effects have led to modifications of the composition of hormonal contraceptive in order to minimize these changes and hence potentially decrease the risks. The synthetic estrogen Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism including estrogen-dependent markers such as liver proteins. This stronger hepatic impact of EE has been related to its 17α-ethinyl group which prevents the inactivation of the molecule and results in a more pronounced hepatic effect of EE as compared to estradiol. Due to its strong activity, administering EE via a non-oral route does not prevent its impact on liver proteins. In order to circumvent the metabolic changes induced by EE, newer products using more natural compounds such as estradiol (E2) and estradiol valerate (E2V) have been introduced. The synthetic progestins used for contraception are structurally related either to testosterone (T) (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to bind more specifically to the progesterone receptor and to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor interactions. Dienogest (DNG), and drospirenone (DRSP

  6. Metabolism of pentachlorophenol by fish

    USGS Publications Warehouse

    Stehly, G.R.; Hayton, W.L.

    1989-01-01

    Interspecies variability in the metabolism of pentachlorophenol (PCP) was investigated by exposing rainbow trout, fathead minnows, sheepshead minnow, firemouth, and goldfish to water-borne super(14)C-PCP for 64 h. The amounts of metabolites in bile and exposure water were species-dependent; all of the metabolites excreted into the water were sulphate conjugates while bile was enriched in glucuronide conjugates. Biliary excretion accounted for less than 30% of the total PCP metabolites. Biliary metabolites alone were a poor indication of the metabolites produced and of the major routes of elimination.

  7. Novel Adipokines and Bone Metabolism

    PubMed Central

    Liu, Yuan; Song, Cheng-Yuan; Wu, Shan-Shan; Liang, Qiu-Hua; Yuan, Ling-Qing; Liao, Er-Yuan

    2013-01-01

    Osteoporosis is a serious social issue nowadays. Both the high morbidity and its common complication osteoporotic fracture load a heavy burden on the whole society. The adipose tissue is the biggest endocrinology organ that has a different function on the bone. The adipocytes are differentiated from the same cell lineage with osteoblast, and they can secrete multiple adipokines with various functions on bone remolding. Recently, several novel adipokines have been identified and investigated thoroughly. In this paper, we would like to highlight the complicated relation between the bone metabolism and the novel adipokines, and it may provide us with a new target for prediction and treatment of osteoporosis. PMID:23431296

  8. Thiophene metabolism by E. coli

    SciTech Connect

    Clark, D.P.

    1990-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur containing heterocyclic molecules such as those found in coal, by mutants of Escherichia coli K-12. We previously isolated multiple mutants of E. coli which were selected for improved oxidation of furan and thiophene derivatives. We have focused on the thdA mutation in our subsequent research as it appears to be of central importance in thiophene oxidation. We hope that analysis of the thd genes of E. coli will lead to improvement of our thiophene metabolizing bacterial strains. 1 tab.

  9. Metabolic analyzer. [for Skylab mission

    NASA Technical Reports Server (NTRS)

    Perry, C. L.

    1973-01-01

    An apparatus is described for the measurement of metabolic rate and breathing dynamics in which inhaled and exhaled breath are sensed by sealed, piston-displacement type spirometers. These spirometers electrically measure the volume of inhaled and exhaled breath. A mass spectrometer analyzes simultaneously for oxygen, carbon dioxide, nitrogen, and water vapor. Circuits responsive to the outputs of the spirometers, mass spectrometer, temperature, pressure, and timing signals compute oxygen consumption, carbon dioxide production, minute volume, and respiratory exchange ratio. A selective indicator provides for readout of these data at predetermined cyclic intervals.

  10. Metabolic Syndrome and Urologic Diseases

    PubMed Central

    Gorbachinsky, Ilya; Akpinar, Haluk; Assimos, Dean G

    2010-01-01

    Metabolic syndrome (MetS) is a complex entity consisting of multiple interrelated factors including insulin resistance, central adiposity, dyslipidemia, endothelial dysfunction and atherosclerotic disease, low-grade inflammation, and in males, low testosterone levels. MetS has been linked to a number of urologic diseases including nephrolithiasis, benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, male infertility, female incontinence, and prostate cancer. This article reviews the relationships between MetS and these entities. Urologists need to be cognizant of the impact that MetS has on urologic diseases as well as on overall patient health. PMID:21234260

  11. [Prostate cancer and metabolic syndrome].

    PubMed

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  12. C. elegans Metabolic Gene Regulatory Networks Govern the Cellular Economy

    PubMed Central

    Watson, Emma; Walhout, Albertha J.M.

    2014-01-01

    Diet greatly impacts metabolism in health and disease. In response to the presence or absence of specific nutrients, metabolic gene regulatory networks sense the metabolic state of the cell and regulate metabolic flux accordingly, for instance by the transcriptional control of metabolic enzymes. Here we discuss recent insights regarding metazoan metabolic regulatory networks using the nematode Caenorhabditis elegans as a model, including the modular organization of metabolic gene regulatory networks, the prominent impact of diet on the transcriptome and metabolome, specialized roles of nuclear hormone receptors in responding to dietary conditions, regulation of metabolic genes and metabolic regulators by microRNAs, and feedback between metabolic genes and their regulators. PMID:24731597

  13. Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies

    PubMed Central

    Kalnenieks, Uldis; Pentjuss, Agris; Rutkis, Reinis; Stalidzans, Egils; Fell, David A.

    2014-01-01

    Mathematical modeling of metabolism is essential for rational metabolic engineering. The present work focuses on several types of modeling approach to quantitative understanding of central metabolic network and energetics in the bioethanol-producing bacterium Zymomonas mobilis. Combined use of Flux Balance, Elementary Flux Mode, and thermodynamic analysis of its central metabolism, together with dynamic modeling of the core catabolic pathways, can help to design novel substrate and product pathways by systematically analyzing the solution space for metabolic engineering, and yields insights into the function of metabolic network, hardly achievable without applying modeling tools. PMID:24550906

  14. Imaging Tumor Metabolism Using Positron Emission Tomography

    PubMed Central

    Lewis, David Y.; Soloviev, Dmitry; Brindle, Kevin M.

    2015-01-01

    Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabelled PET substrates can be traced at sub-physiological concentrations, allowing non-invasive imaging of metabolism and intra-tumoral heterogeneity in systems ranging from advanced cancer models to cancer patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of tumor metabolism, including carbohydrate, amino acid and fatty acid metabolism. In this review we will briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism will be considered alongside new technical developments, such as combined PET/MRI machines, that could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine. PMID:25815854

  15. Metabolic alterations accompanying oncogene-induced senescence

    PubMed Central

    Aird, Katherine M; Zhang, Rugang

    2014-01-01

    Senescence is defined as a stable cell growth arrest. Oncogene-induced senescence (OIS) occurs in normal primary human cells after activation of an oncogene in the absence of other cooperating oncogenic stimuli. OIS is therefore considered a bona fide tumor suppression mechanism in vivo. Indeed, overcoming OIS-associated stable cell growth arrest can lead to tumorigenesis. Although cells that have undergone OIS do not replicate their DNA, they remain metabolically active. A number of recent studies report significant changes in cellular metabolism during OIS, including alterations in nucleotide, glucose, and mitochondrial metabolism and autophagy. These alterations may be necessary for stable senescence-associated cell growth arrest, and overcoming these shifts in metabolism may lead to tumorigenesis. This review highlights what is currently known about alterations in cellular metabolism during OIS and the implication of OIS-associated metabolic changes in cellular transformation and the development of cancer therapeutic strategies. PMID:27308349

  16. Modeling Glucose Metabolism in the Kidney.

    PubMed

    Chen, Ying; Fry, Brendan C; Layton, Anita T

    2016-06-01

    The mammalian kidney consumes a large amount of energy to support the reabsorptive work it needs to excrete metabolic wastes and to maintain homeostasis. Part of that energy is supplied via the metabolism of glucose. To gain insights into the transport and metabolic processes in the kidney, we have developed a detailed model of the renal medulla of the rat kidney. The model represents water and solute flows, transmural fluxes, and biochemical reactions in the luminal fluid of the nephrons and vessels. In particular, the model simulates the metabolism of oxygen and glucose. Using that model, we have identified parameters concerning glucose transport and basal metabolism that yield predicted blood glucose concentrations that are consistent with experimental measurements. The model predicts substantial axial gradients in blood glucose levels along various medullary structures. Furthermore, the model predicts that in the inner medulla, owing to the relatively limited blood flow and low tissue oxygen tension, anaerobic metabolism of glucose dominates. PMID:27371260

  17. Metabolic model for diversity-generating biosynthesis.

    PubMed

    Tianero, Ma Diarey; Pierce, Elizabeth; Raghuraman, Shrinivasan; Sardar, Debosmita; McIntosh, John A; Heemstra, John R; Schonrock, Zachary; Covington, Brett C; Maschek, J Alan; Cox, James E; Bachmann, Brian O; Olivera, Baldomero M; Ruffner, Duane E; Schmidt, Eric W

    2016-02-16

    A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds. Intermediates are long lived and accumulate progressively, in contrast with conventional metabolic pathways, in which the first step is rate-limiting and metabolic intermediates are short-lived. Understanding these fundamental differences enables several different practical applications, such as combinatorial biosynthesis, some of which we demonstrate here. We propose that these principles may provide a unifying framework underlying diversity-generating metabolism in many different biosynthetic pathways. PMID:26831074

  18. Targeting cancer cell metabolism in pancreatic adenocarcinoma

    PubMed Central

    Cohen, Romain; Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Faivre, Sandrine; de Gramont, Armand; Raymond, Eric

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided. PMID:26164081

  19. Metabolic flux rewiring in mammalian cell cultures.

    PubMed

    Young, Jamey D

    2013-12-01

    Continuous cell lines (CCLs) engage in 'wasteful' glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phenotype, but instead can shift their metabolism toward increased oxidative metabolism as nutrients become depleted and/or growth rate slows. Progress to understand dynamic flux regulation in CCLs has enabled the development of novel strategies to force cultures into desirable metabolic phenotypes, by combining fed-batch feeding strategies with direct metabolic engineering of host cells. PMID:23726154

  20. Metabolic model for diversity-generating biosynthesis

    PubMed Central

    Tianero, Ma. Diarey; Pierce, Elizabeth; Raghuraman, Shrinivasan; Sardar, Debosmita; McIntosh, John A.; Heemstra, John R.; Schonrock, Zachary; Covington, Brett C.; Maschek, J. Alan; Cox, James E.; Bachmann, Brian O.; Olivera, Baldomero M.; Ruffner, Duane E.; Schmidt, Eric W.

    2016-01-01

    A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds. Intermediates are long lived and accumulate progressively, in contrast with conventional metabolic pathways, in which the first step is rate-limiting and metabolic intermediates are short-lived. Understanding these fundamental differences enables several different practical applications, such as combinatorial biosynthesis, some of which we demonstrate here. We propose that these principles may provide a unifying framework underlying diversity-generating metabolism in many different biosynthetic pathways. PMID:26831074

  1. Chinese Herbs Interfering with Cancer Reprogramming Metabolism

    PubMed Central

    Zhong, Zhangfeng; Qiang, William W.; Tan, Wen; Zhang, Haotian; Wang, Shengpeng; Wang, Chunming; Qiang, Wenan; Wang, Yitao

    2016-01-01

    Emerging evidence promotes a reassessment of metabolic reprogramming regulation in cancer research. Although there exists a long history of Chinese herbs applied in cancer treatment, few reports have addressed the effects of Chinese herbal components on metabolic reprogramming, which is a central cancer hallmark involved in the slowing or prevention of chemoresistance in cancer cells. In this review, we have focused on four core elements altered by metabolic reprogramming in cancer cells. These include glucose transport, glycolysis, mitochondrial oxidative phosphorylation, and fatty acid synthesis. With this focus, we have summarized recent advances in metabolic reprogramming of cancer cells in response to specific Chinese herbal components. We propose that exploring Chinese herbal interference in cancer metabolic reprogramming might identify new therapeutic targets for cancer and more ways in which to approach metabolism-related diseases. PMID:27242914

  2. RNA Regulation of Lipotoxicity and Metabolic Stress.

    PubMed

    Caputa, George; Schaffer, Jean E

    2016-07-01

    Noncoding RNAs are an emerging class of nonpeptide regulators of metabolism. Metabolic diseases and the altered metabolic environment induce marked changes in levels of microRNAs and long noncoding RNAs. Furthermore, recent studies indicate that a growing number of microRNAs and long noncoding RNAs serve as critical mediators of adaptive and maladaptive responses through their effects on gene expression. The metabolic environment also has a profound impact on the functions of classes of noncoding RNAs that have been thought primarily to subserve housekeeping functions in cells-ribosomal RNAs, transfer RNAs, and small nucleolar RNAs. Evidence is accumulating that these RNAs are also components of an integrated cellular response to the metabolic milieu. This Perspective discusses the different classes of noncoding RNAs and their contributions to the pathogenesis of metabolic stress. PMID:27288006

  3. A Diagnostic Algorithm for Metabolic Myopathies

    PubMed Central

    Berardo, Andres; DiMauro, Salvatore

    2010-01-01

    Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). PMID:20425236

  4. Chronic ketosis and cerebral metabolism.

    PubMed

    DeVivo, D C; Leckie, M P; Ferrendelli, J S; McDougal, D B

    1978-04-01

    The effects of chronic ketosis on cerebral metabolism were determined in adult rats maintained on a high-fat diet for approximately three weeks and compared to a control group of animals. The fat-fed rats had statistically significantly lower blood glucose concentrations and higher blood beta-hydroxybutyrate and acetoacetate concentrations; higher brain concentrations of bound glucose, glucose 6-phosphate, pyruvate, lactate, beta-hydroxybutyrate, citrate, alpha-ketoglutarate, alanine, and adenosine triphosphate (ATP); lower brain concentrations of fructose 1,6-diphosphate, aspartate, adenosine diphosphate (ADP), creatine, cyclic nucleotides, succinyl coenzyme A (CoA), acid-insoluble CoA, and total CoA; and similar brain concentrations of glucose, malate, calculated oxaloacetate, glutamate, glutamine, adenosine monophosphate, phosphocreatine, reduced CoA, acetyl CoA, sodium, potassium, chloride, and water content. The metabolite data in the chronically ketotic rats demonstrate an increase in the cerebral energy reserve and energy charge. These data also suggest negative modification of the enzymes phosphofructokinase, pyruvic dehydrogenase, and alpha-ketoglutaric dehydrogenase; positive modification of glycogen synthase; and possible augmentation of the hexose transport system. There was no demonstrable difference in brain pH, water content, or electrolytes in the two groups of animals. We speculate that the increased brain ATP/ADP ratio is central to most, if not all, the observed metabolic perturbations and may account for the increased neuronal stability that accompanies chronic ketosis. PMID:666275

  5. Metabolic Causes of Epileptic Encephalopathy

    PubMed Central

    Pearl, Phillip L.

    2013-01-01

    Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547

  6. Representations of metabolic knowledge: pathways.

    PubMed

    Karp, P D; Paley, S M

    1994-01-01

    The automatic generation of drawings of metabolic pathways is a challenging problem that depends intimately on exactly what information has been recorded for each pathway, and on how that information is encoded. The chief contributions of the paper are a minimized representation for biochemical pathways called the predecessor list, and inference procedures for converting the predecessor list into a pathway-graph representation that can serve as input to a pathway-drawing algorithm. The predecessor list has several advantages over the pathway graph, including its compactness and its lack of redundancy. The conversion between the two representations can be formulated as both a constraint-satisfaction problem and a logical inference problem, whose goal is to assign directions to reactions, and to determine which are the main chemical compounds in the reaction. We describe a set of production rules that solves this inference problem. We also present heuristics for inferring whether the exterior compounds that are substrates of reactions at the periphery of a pathway are side or main compounds. These techniques were evaluated on 18 metabolic pathways from the EcoCyc knowledge base. PMID:7584392

  7. Bacterial metabolism of hydroxylated biphenyls.

    PubMed Central

    Higson, F K; Focht, D D

    1989-01-01

    Isolates able to grow on 3- or 4-hydroxybiphenyl (HB) as the sole carbon source were obtained by enrichment culture. The 3-HB degrader Pseudomonas sp. strain FH12 used an NADPH-dependent monooxygenase restricted to 3- and 3,3'-HBs to introduce an ortho-hydroxyl. The 4-HB degrader Pseudomonas sp. strain FH23 used either a mono- or dioxygenase to generate a 2,3-diphenolic substitution pattern which allowed meta-fission of the aromatic ring. By using 3-chlorocatechol to inhibit catechol dioxygenase activity, it was found that 2- and 3-HBs were converted by FH23 to 2,3-HB, whereas biphenyl and 4-HB were attacked by dioxygenation. 4-HB was metabolized to 2,3,4'-trihydroxybiphenyl. Neither organism attacked chlorinated HBs. The degradation of 3- and 4-HBs by these strains is therefore analogous to the metabolism of biphenyl, 2-HB, and naphthalene in the requirement for 2,3-catechol formation. PMID:2729993

  8. Carbohydrate Metabolism in Spirochaeta stenostrepta

    PubMed Central

    Hespell, Robert B.; Canale-Parola, E.

    1970-01-01

    The pathways of carbohydrate metabolism in Spirochaeta stenostrepta, a free-living, strictly anaerobic spirochete, were studied. The organism fermented glucose to ethyl alcohol, acetate, lactate, CO2, and H2. Assays of enzymatic activities in cell extracts, and determinations of radioactivity distribution in products formed from 14C-labeled glucose indicated that S. stenostrepta degraded glucose via the Embden-Meyerhof pathway. The spirochete utilized a clostridial-type clastic reaction to metabolize pyruvate to acetyl-coenzyme A, CO2, and H2, without production of formate. Acetyl-coenzyme A was converted to ethyl alcohol by nicotinamide adenine dinucleotide-dependent acetaldehyde and alcohol dehydrogenase activities. Phosphotransacetylase and acetate kinase catalyzed the formation of acetate from acetyl-coenzyme A. Hydrogenase and lactate dehydrogenase activities were detected in cell extracts. A rubredoxin was isolated from cell extracts of S. stenostrepta. Preparations of this rubredoxin stimulated acetyl phosphate formation from pyruvate by diethylaminoethyl cellulose-treated extracts of S. stenostrepta, an indication that rubredoxin may participate in pyruvate cleavage by this spirochete. Nutritional studies showed that S. stenostrepta fermented a variety of carbohydrates, but did not ferment amino acids or other organic acids. An unidentified growth factor present in yeast extract was required by the organism. Exogenous supplements of biotin, riboflavin, and vitamin B12 were either stimulatory or required for growth. PMID:5423371

  9. The origin of intermediary metabolism.

    PubMed

    Morowitz, H J; Kostelnik, J D; Yang, J; Cody, G D

    2000-07-01

    The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique. PMID:10859347

  10. Male hypogonadism and metabolic syndrome.

    PubMed

    Naifar, M; Rekik, N; Messedi, M; Chaabouni, K; Lahiani, A; Turki, M; Abid, M; Ayedi, F; Jamoussi, K

    2015-06-01

    The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link. PMID:25040289

  11. Bacterial metabolism of 4-chlorophenoxyacetate

    PubMed Central

    Evans, W. C.; Smith, B. S. W.; Moss, P.; Fernley, H. N.

    1971-01-01

    1. A pseudomonad capable of utilizing 4-chlorophenoxyacetate (CPA) as sole source of organic carbon was isolated from soil. 2. The organism was grown in liquid culture and the following compounds were isolated and identified in culture extracts: 4-chloro-2-hydroxyphenoxyacetate, 4-chlorocatechol, β-chloromuconate probably the cis–trans isomer and γ-carboxymethylene-Δαβ-butenolide. 3. Cells grown on 4-chlorophenoxyacetate were able to metabolize 4-chloro-2-hydroxyphenoxyacetate, 4-chlorocatechol and γ-carboxymethylene-Δαβ-butenolide without a lag period. They were not adapted to 4-chlorophenol, or to either culture isolated or synthetic β-chloromuconate, possibly because of stereospecificity towards the cis–cis isomer. 4. On the basis of isolation and induction evidence, the following metabolic pathway is proposed for the breakdown of 4-chlorophenoxyacetate by this organism: 4-chlorophenoxyacetate → 4-chloro-2-hydroxyphenoxyacetate → 4-chlorocatechol → cis–cis-β-chloromuconate → γ-carboxymethylene-Δαβ-butenolide → maleylacetate and fumarylacetate → fumarate and acetate. PMID:5123884

  12. Carbohydrate metabolism in Spirochaeta stenostrepta.

    PubMed

    Hespell, R B; Canale-Parola, E

    1970-07-01

    The pathways of carbohydrate metabolism in Spirochaeta stenostrepta, a free-living, strictly anaerobic spirochete, were studied. The organism fermented glucose to ethyl alcohol, acetate, lactate, CO(2), and H(2). Assays of enzymatic activities in cell extracts, and determinations of radioactivity distribution in products formed from (14)C-labeled glucose indicated that S. stenostrepta degraded glucose via the Embden-Meyerhof pathway. The spirochete utilized a clostridial-type clastic reaction to metabolize pyruvate to acetyl-coenzyme A, CO(2), and H(2), without production of formate. Acetyl-coenzyme A was converted to ethyl alcohol by nicotinamide adenine dinucleotide-dependent acetaldehyde and alcohol dehydrogenase activities. Phosphotransacetylase and acetate kinase catalyzed the formation of acetate from acetyl-coenzyme A. Hydrogenase and lactate dehydrogenase activities were detected in cell extracts. A rubredoxin was isolated from cell extracts of S. stenostrepta. Preparations of this rubredoxin stimulated acetyl phosphate formation from pyruvate by diethylaminoethyl cellulose-treated extracts of S. stenostrepta, an indication that rubredoxin may participate in pyruvate cleavage by this spirochete. Nutritional studies showed that S. stenostrepta fermented a variety of carbohydrates, but did not ferment amino acids or other organic acids. An unidentified growth factor present in yeast extract was required by the organism. Exogenous supplements of biotin, riboflavin, and vitamin B(12) were either stimulatory or required for growth. PMID:5423371

  13. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  14. Sex steroids and glucose metabolism.

    PubMed

    Allan, Carolyn A

    2014-01-01

    Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM) and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference) is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain. PMID:24457840

  15. The origin of intermediary metabolism

    NASA Technical Reports Server (NTRS)

    Morowitz, H. J.; Kostelnik, J. D.; Yang, J.; Cody, G. D.

    2000-01-01

    The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO(2) and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique.

  16. Metabolic Dysfunction in Diabetic Cardiomyopathy

    PubMed Central

    Isfort, Michael; Stevens, Sarah C.W.; Schaffer, Stephen; Jong, Chian Ju; Wold, Loren E.

    2013-01-01

    Diabetic cardiomyopathy (DCM) is defined as cardiac disease independent of vascular complications during diabetes. The number of new cases of DCM is rising at epidemic rates in proportion to newly diagnosed cases of diabetes mellitus (DM) throughout the world. DCM is a heart failure syndrome found in diabetic patients that is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction, occurring in the absence of hypertension and coronary artery disease. DCM and other diabetic complications are caused in part by elevations in blood glucose and lipids, characteristic of DM. Although there are pathological consequences to hyperglycemia and hyperlipidemia, the combination of the two metabolic abnormalities potentiates the severity of diabetic complications. A natural competition exists between glucose and fatty acid metabolism in the heart that is regulated by allosteric and feedback control and transcriptional modulation of key limiting enzymes. Inhibition of these glycolytic enzymes not only controls flux of substrate through the glycolytic pathway, but also leads to the diversion of glycolytic intermediate substrate through pathological pathways, which mediate the onset of diabetic complications. The present review describes the limiting steps involved in the development of these pathological pathways and the factors involved in the regulation of these limiting steps. Additionally, therapeutic options with demonstrated or postulated effects on DCM are described. PMID:23443849

  17. Benzodiazepine metabolism: an analytical perspective.

    PubMed

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria Augusta

    2008-10-01

    Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam. PMID:18855614

  18. The origin of intermediary metabolism

    PubMed Central

    Morowitz, Harold J.; Kostelnik, Jennifer D.; Yang, Jeremy; Cody, George D.

    2000-01-01

    The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO2 and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. To inquire into the reaction networks that might emerge, we start with the largest available database of organic molecules, Beilstein on-line, and prune by a set of physical and chemical constraints applicable to the model system. From the 3.5 million entries in Beilstein we emerge with 153 molecules that contain all 11 members of the reductive citric acid cycle. A small number of selection rules generates a very constrained subset, suggesting that this is the type of reaction model that will prove useful in the study of biogenesis. The model indicates that the metabolism shown in the universal chart of pathways may be central to the origin of life, is emergent from organic chemistry, and may be unique. PMID:10859347

  19. Metabolism of carbon in soybean

    SciTech Connect

    Johnson, K.A.; McManus, E.E.; Conboy, J.J.

    1996-10-01

    The distribution and metabolism of {sup 14}C-carboxin [5,6 dihydro-2-methyl-N-phenyl-1,4-oxathiin-3-carboxamide] in the food and feed commodities of soybean were determined. Soybeans were grown to maturity indoors from seeds treated with {sup 14}C-carboxin at the normal use rate (1X) and two exaggerated rates (5X and 10X). The level of radioactivity was highest in the foliage, (12.5 ppm, 110 ppm, and 169 ppm for the low to high dose groups, respectively), and lowest in the seeds, (0.51 ppm, 2.077 ppm and 4.63 ppm, respectively). Extractable radioactivity accounted for approx. 75, 80, and 90% in the pods, seed, and foliage, respectively. Enzymatic hydrolysis of the post extracted solids released an additional 10, 15, and 5% radioactivity for the sum matrices, respectively. The major routes of metabolism were characterized by the oxidation of sulfur, cleavage of the oxathiim ring, and conjugation with glucose as shown below. These metabolites in soybean represent the most extensive modifications of carboxin observed in any plant system studied.

  20. The metabolism of 3-benzoylpyridine.

    PubMed

    Eyer, P; Hell, W

    1983-11-01

    3-Benzoylpyridine (3-BP), a decomposition product of the soman antidote, HGG-12 (3-benzoylpyridino(1)-methyl 2'-hydroxyiminomethylpyridino(1')methyl ether dichloride) was rapidly metabolized in the isolated perfused rat liver, giving 3-(alpha-hydroxybenzyl)pyridine and its corresponding glucuronide, 3-benzoylpyridine-N-oxide, and 3-(alpha-hydroxybenzyl)pyridine-N-oxide. The latter is formed both from 3-(alpha-hydroxybenzyl)pyridine and 3-benzoylpyridine-N-oxide. Metabolism of 3-BP studied in rats and dogs in vivo revealed significant species differences. In rat, 80% of 14C-3-BP was excreted as N-oxides and alpha-hydroxybenzyl derivatives in the urine. In dogs, 95% dose was excreted in urine mostly as the glucuronide of 3-(alpha-hydroxybenzyl)pyridine and as the quaternary pyridinium compounds, 3-benzoyl-1-methylpyridinium and 3-(alpha-hydroxybenzyl)-1-methylpyridinium. These latter were hardly detected in rat urine. In contrast to rats, the N-oxides were present only in small amounts in dog urine. PMID:6673376

  1. Simulating Metabolism with Statistical Thermodynamics

    SciTech Connect

    Cannon, William R.

    2014-08-04

    Kinetic probabilities of state are usually based on empirical measurements, while thermodynamic state probabilities are based on the assumption that chemical species are distributed to according to a multinomial Boltzmann distribution. While the use of kinetic simulations is desirable, obtaining all the mass action rate constants necessary to carry out kinetic simulations is an overwhelming challenge. Here, the kinetic probability of a state is compared in depth to the thermodynamic probability of a state for sets of coupled reactions. The entropic and energetic contributions to thermodynamic stable states are described and compared to entropic and energetic contributions of kinetic steady states. It is shown that many kinetic steady states are possible for a system of coupled reactions depending on the relative values of the mass action rate constants, but only one of these corresponds to a thermodynamically stable state. Furthermore, the thermodynamic stable state corresponds to a minimum free energy state. The use of thermodynamic simulations of state to model metabolic processes is attractive, since metabolite levels and energy requirements of pathways can be evaluated using only standard free energies of formation as parameters in the probability distribution. In chemical physics, the assumption of a Boltzmann distribution is the basis of transition state theory for modeling transitory species. Application to stable species, such as those found in metabolic processes, is a less severe assumption that would enable the use of simulations of state.

  2. [METABOLIC INTOXICATION IN THERMIC TRAUMA].

    PubMed

    Kovalenko, O M

    2015-05-01

    In 76 injured persons with deep and superficial burns, having area from 3 to 65% of the total body surface and ageing 5-16 yrs old, there was investigated the impact of early surgical treatment on the metabolic intoxication severity in accordance to content of the oxidatively modified proteins carbonyl groups in the blood serum, and of a ceruloplasmin, what was considered as integral express-index of the organism antioxidant system state. Changes of these indices in ambustial disease of middle severity have witnessed a sufficiently compensated reaction of organism: of severe and extremely severe one--there were noted a deficiency of the organism antioxidant defense; and in stages of toxemia and septicotoxemia--attrition of the organism oxidant reserves and danger of the septic complications occurrence. Conduction of early surgical intervention have guaranteed maintenance of a ceruloplasmin content in stages of toxemia and septicotoxemia on the level of healthy persons, relief of the ambustial disease course, absence of critical metabolic intoxication and carbonyl stress, reduction of the septic complications rate in 1.5 times. PMID:26419044

  3. Intermediate Energy Metabolism of Leptospira

    PubMed Central

    Baseman, J. B.; Cox, C. D.

    1969-01-01

    Metabolic studies were performed on three representative serotypes of Leptospira: a water isolate designated B16 and two pathogenic serotypes, pomona and schueffneri. Examination of whole cells of B16 for their ability to oxidize various substrates revealed that oleate significantly stimulated oxygen uptake. The respiratory quotient of 0.7 implied that oleate was degraded to carbon dioxide and water. Other substrates, such as carbohydrates, alcohols, intermediates of the citric acid cycle, and short-chain acids, including selected amino acids, did not stimulate endogenous respiration of whole cells. No oxygen uptake could be measured when cell-free extracts were tested with the substrates used with whole cells. Enzymatic analyses of cell-free extracts of the three strains demonstrated enzymes of the citric acid cycle, enzymes of the glycolytic and pentose pathways, and the general acyl coenzyme A dehydrogenase required for β-oxidation of fatty acids. Strain B16 and the two pathogenic serotypes appeared to possess similar metabolic capabilities. Enzymatic data might also explain the apparent inability of B16 to oxidize other substrates; kinases necessary for activation of common nonphosphorylated compounds were not detected in leptospiral extracts. These findings emphasized the dependence of leptospiral growth upon long-chain fatty acids. PMID:5776541

  4. The Evolution of Fungal Metabolic Pathways

    PubMed Central

    Rokas, Antonis

    2014-01-01

    Fungi contain a remarkable range of metabolic pathways, sometimes encoded by gene clusters, enabling them to digest most organic matter and synthesize an array of potent small molecules. Although metabolism is fundamental to the fungal lifestyle, we still know little about how major evolutionary processes, such as gene duplication (GD) and horizontal gene transfer (HGT), have interacted with clustered and non-clustered fungal metabolic pathways to give rise to this metabolic versatility. We examined the synteny and evolutionary history of 247,202 fungal genes encoding enzymes that catalyze 875 distinct metabolic reactions from 130 pathways in 208 diverse genomes. We found that gene clustering varied greatly with respect to metabolic category and lineage; for example, clustered genes in Saccharomycotina yeasts were overrepresented in nucleotide metabolism, whereas clustered genes in Pezizomycotina were more common in lipid and amino acid metabolism. The effects of both GD and HGT were more pronounced in clustered genes than in their non-clustered counterparts and were differentially distributed across fungal lineages; specifically, GD, which was an order of magnitude more abundant than HGT, was most frequently observed in Agaricomycetes, whereas HGT was much more prevalent in Pezizomycotina. The effect of HGT in some Pezizomycotina was particularly strong; for example, we identified 111 HGT events associated with the 15 Aspergillus genomes, which sharply contrasts with the 60 HGT events detected for the 48 genomes from the entire Saccharomycotina subphylum. Finally, the impact of GD within a metabolic category was typically consistent across all fungal lineages, whereas the impact of HGT was variable. These results indicate that GD is the dominant process underlying fungal metabolic diversity, whereas HGT is episodic and acts in a category- or lineage-specific manner. Both processes have a greater impact on clustered genes, suggesting that metabolic gene clusters

  5. Oncometabolites: linking altered metabolism with cancer

    PubMed Central

    Yang, Ming; Soga, Tomoyoshi; Pollard, Patrick J.

    2013-01-01

    The discovery of cancer-associated mutations in genes encoding key metabolic enzymes has provided a direct link between altered metabolism and cancer. Advances in mass spectrometry and nuclear magnetic resonance technologies have facilitated high-resolution metabolite profiling of cells and tumors and identified the accumulation of metabolites associated with specific gene defects. Here we review the potential roles of such “oncometabolites” in tumor evolution and as clinical biomarkers for the detection of cancers characterized by metabolic dysregulation. PMID:23999438

  6. Modelling metabolism of the diatom Phaeodactylum tricornutum.

    PubMed

    Singh, Dipali; Carlson, Ross; Fell, David; Poolman, Mark

    2015-12-01

    Marine diatoms have potential as a biotechnological production platform, especially for lipid-derived products, including biofuels. Here we introduce some features of diatom metabolism, particularly with respect to photosynthesis, photorespiration and lipid synthesis and their differences relative to other photosynthetic eukaryotes. Since structural metabolic modelling of other photosynthetic organisms has been shown to be capable of representing their metabolic capabilities realistically, we briefly review the main approaches to this type of modelling. We then propose that genome-scale modelling of the diatom Phaeodactylum tricornutum, in response to varying light intensity, could uncover the novel aspects of the metabolic potential of this organism. PMID:26614658

  7. Mitochondrial Division and Fusion in Metabolism

    PubMed Central

    Roy, Madhuparna; Reddy, P. Hemachandra; Iijima, Miho; Sesaki, Hiromi

    2015-01-01

    Mitochondria govern many metabolic processes. In addition, mitochondria sense the status of metabolism and change their functions to regulate energy production, cell death, and thermogenesis. Recent studies have revealed that mitochondrial structural remodeling through division and fusion is critical to the organelle’s function. It has also become clear that abnormalities in mitochondrial division and fusion are linked to the pathophysiology of metabolic diseases such as diabetes and obesity. Here, we discuss the current understanding of the mechanisms of mitochondrial dynamics and their role in cellular and organismal metabolism. PMID:25703628

  8. Neuroprotection in Metabolism-Based Therapy

    PubMed Central

    Hartman, Adam L.

    2011-01-01

    Metabolism-based therapy has been used successfully in the treatment of seizures but study of its use in other neurodegenerative disorders is growing. Data demonstrating the use of different forms of metabolism-based therapy in human trials of Alzheimer disease and Parkinson disease are discussed. Animal and in vitro studies have shed light on metabolism-based therapy’s mechanisms in these diseases, as well as ALS, aging, ischemia, trauma and mitochondrial cytopathies. Additional insights may be obtained by considering the role of metabolism-based therapy in cell disability and death (specifically apoptosis, excitotoxicity, and autophagy). PMID:21872441

  9. Parma consensus statement on metabolic disruptors.

    PubMed

    Heindel, Jerrold J; vom Saal, Frederick S; Blumberg, Bruce; Bovolin, Patrizia; Calamandrei, Gemma; Ceresini, Graziano; Cohn, Barbara A; Fabbri, Elena; Gioiosa, Laura; Kassotis, Christopher; Legler, Juliette; La Merrill, Michele; Rizzir, Laura; Machtinger, Ronit; Mantovani, Alberto; Mendez, Michelle A; Montanini, Luisa; Molteni, Laura; Nagel, Susan C; Parmigiani, Stefano; Panzica, Giancarlo; Paterlini, Silvia; Pomatto, Valentina; Ruzzin, Jérôme; Sartor, Giorgio; Schug, Thaddeus T; Street, Maria E; Suvorov, Alexander; Volpi, Riccardo; Zoeller, R Thomas; Palanza, Paola

    2015-01-01

    A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome. PMID:26092037

  10. Systems Metabolic Engineering of Escherichia coli.

    PubMed

    Choi, Kyeong Rok; Shin, Jae Ho; Cho, Jae Sung; Yang, Dongsoo; Lee, Sang Yup

    2016-05-01

    Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass. PMID:27223822

  11. Epigenetic methylations and their connections with metabolism.

    PubMed

    Chiacchiera, Fulvio; Piunti, Andrea; Pasini, Diego

    2013-05-01

    Metabolic pathways play fundamental roles in several processes that regulate cell physiology and adaptation to environmental changes. Altered metabolic pathways predispose to several different pathologies ranging from diabetes to cancer. Specific transcriptional programs tightly regulate the enzymes involved in cell metabolism and dictate cell fate regulating the differentiation into specialized cell types that contribute to metabolic adaptation in higher organisms. For these reasons, it is of extreme importance to identify signaling pathways and transcription factors that positively and negatively regulate metabolism. Genomic organization allows a plethora of different strategies to regulate transcription. Importantly, large evidence suggests that the quality of diet and the caloric regimen can influence the epigenetic state of our genome and that certain metabolic pathways are also epigenetically controlled reveling a tight crosstalk between metabolism and epigenomes. Here we focus our attention on methylation-based epigenetic reactions, on how different metabolic pathways control these activities, and how these can influence metabolism. Altogether, the recent discoveries linking these apparent distant areas reveal that an exciting field of research is emerging. PMID:23456257

  12. Metabolic Flexibility: Hibernation, Torpor, and Estivation.

    PubMed

    Staples, James F

    2016-04-01

    Many environmental conditions can constrain the ability of animals to obtain sufficient food energy, or transform that food energy into useful chemical forms. To survive extended periods under such conditions animals must suppress metabolic rate to conserve energy, water, or oxygen. Amongst small endotherms, this metabolic suppression is accompanied by and, in some cases, facilitated by a decrease in core body temperature-hibernation or daily torpor-though significant metabolic suppression can be achieved even with only modest cooling. Within some ectotherms, winter metabolic suppression exceeds the passive effects of cooling. During dry seasons, estivating ectotherms can reduce metabolism without changes in body temperature, conserving energy reserves, and reducing gas exchange and its inevitable loss of water vapor. This overview explores the similarities and differences of metabolic suppression among these states within adult animals (excluding developmental diapause), and integrates levels of organization from the whole animal to the genome, where possible. Several similarities among these states are highlighted, including patterns and regulation of metabolic balance, fuel use, and mitochondrial metabolism. Differences among models are also apparent, particularly in whether the metabolic suppression is intrinsic to the tissue or depends on the whole-animal response. While in these hypometabolic states, tissues from many animals are tolerant of hypoxia/anoxia, ischemia/reperfusion, and disuse. These natural models may, therefore, serve as valuable and instructive models for biomedical research. PMID:27065167

  13. [Tryptophan metabolism and oligophrenia (author's transl)].

    PubMed

    Grimm, U; Knapp, A; Schmitz, W; Smetan, M; Schmitz, K W; Reddemann, H; Schulz, M; Schlenzka, K

    1978-04-01

    After dealing with the biochemistry of tryptophan metabolism the most important results obtained in humans are presented. Special emphasis is given to the hereditary defects of tryptophan metabolism associated with mental retardation and convulsions due to lack of pyridoxine. The author's findings demonstrate the existence of a hereditary disturbance of the tryptophan metabolism via kynurenine in a certain part of oligophrenic patients. This metabolic defect can be controlled by high doses of vitamin B6. Furthermore investigations conducted with a view to interpreting these results are discussed, especially the determination of kynureninase activity, serotonin blood levels and pyridine nucleotide synthesis. PMID:147846

  14. Portable Unit for Metabolic Analysis

    NASA Technical Reports Server (NTRS)

    Dietrich, Daniel L.; Pitch, Nancy D.; Lewis, Mark E.; Juergens, Jeffrey R.; Lichter, Michael J.; Stuk, Peter M.; Diedrick, Dale M.; Valentine, Russell W.; Pettegrew, Richard D.

    2007-01-01

    The Portable Unit for Metabolic Analysis (PUMA) is an instrument that measures several quantities indicative of human metabolic function. Specifically, this instrument makes time-resolved measurements of temperature, pressure, flow, and the partial pressures of oxygen and carbon dioxide in breath during both inhalation and exhalation. Portable instruments for measuring these quantities have been commercially available, but the response times of those instruments are too long to enable temporal resolution of phenomena on the time scales of human respiration cycles. In contrast, the response time of the PUMA is significantly shorter than characteristic times of human respiration phenomena, making it possible to analyze varying metabolic parameters, not only on sequential breath cycles but also at successive phases of inhalation and exhalation within the same breath cycle. In operation, the PUMA is positioned to sample breath near the subject s mouth. Commercial off-the-shelf sensors are used for three of the measurements: a miniature pressure transducer for pressure, a thermistor for temperature, and an ultrasonic sensor for flow. Sensors developed at Glenn Research Center are used for measuring the partial pressures of oxygen and carbon dioxide: The carbon dioxide sensor exploits the relatively strong absorption of infrared light by carbon dioxide. Light from an infrared source passes through the stream of inhaled or exhaled gas and is focused on an infrared- sensitive photodetector. The oxygen sensor exploits the effect of oxygen in quenching the fluorescence of ruthenium-doped organic molecules in a dye on the tip of an optical fiber. A blue laser diode is used to excite the fluorescence, and the optical fiber carries the fluorescent light to a photodiode, the temporal variation of the output of which bears a known relationship with the rate of quenching of fluorescence and, hence, with the partial pressure of oxygen. The outputs of the sensors are digitized

  15. Microbial Metabolism in Serpentinite Fluids

    NASA Astrophysics Data System (ADS)

    Crespo-Medina, M.; Brazelton, W. J.; Twing, K. I.; Kubo, M.; Hoehler, T. M.; Schrenk, M. O.

    2013-12-01

    Serpentinization is the process in which ultramafic rocks, characteristic of the upper mantle, react with water liberating mantle carbon and reducing power to potenially support chemosynthetic microbial communities. These communities may be important mediators of carbon and energy exchange between the deep Earth and the surface biosphere. Our work focuses on the Coast Range Ophiolite Microbial Observatory (CROMO) in Northern California where subsurface fluids are accessible through a series of wells. Preliminary analyses indicate that the highly basic fluids (pH 9-12) have low microbial diversity, but there is limited knowledge about the metabolic capabilities of these communties. Metagenomic data from similar serpentine environments [1] have identified Betaproteobacteria belonging to the order Burkholderiales and Gram-positive bacteria from the order Clostridiales as key components of the serpentine microbiome. In an effort to better characterize the microbial community, metabolism, and geochemistry at CROMO, fluids from two representative wells (N08B and CSWold) were sampled during recent field campaigns. Geochemical characterization of the fluids includes measurements of dissolved gases (H2, CO, CH4), dissolved inorganic and organic carbon, volatile fatty acids, and nutrients. The wells selected can be differentiated in that N08B had higher pH (10-11), lower dissolved oxygen, and cell counts ranging from 105-106 cells mL-1 of fluid, with an abundance of the betaproteobacterium Hydrogenophaga. In contrast, fluids from CSWold have slightly lower pH (9-9.5), DO, and conductivity, as well as higher TDN and TDP. CSWold fluid is also characterized for having lower cell counts (~103 cells mL-1) and an abundance of Dethiobacter, a taxon within the phylum Clostridiales. Microcosm experiments were conducted with the purpose of monitoring carbon fixation, methanotrophy and metabolism of small organic compounds, such as acetate and formate, while tracing changes in fluid

  16. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  17. The metabolism of methoxyethylmercury salts

    PubMed Central

    Daniel, J. W.; Gage, J. C.; Lefevre, P. A.

    1971-01-01

    The metabolism of methoxy[14C]ethylmercury chloride in the rat has been investigated. After a single subcutaneous dose a small proportion is excreted unchanged in urine and a larger amount in bile with some resorption from the gut. The greater part of the dose is rapidly broken down in the tissues with a half-time of about 1 day to yield ethylene and inorganic mercury. Ethylene is exhaled in the breath and the mercury migrates to the kidney and is excreted in urine. A small proportion of the dose appears as carbon dioxide in the breath and about 12% in urine as a mercury-free metabolite. It is possible that the breakdown of methoxyethylmercurychloride to ethylene and inorganic mercury is not catalysed by an enzyme system. PMID:5119773

  18. Metabolic effects of smoking cessation

    PubMed Central

    Harris, Kindred K.; Zopey, Mohan; Friedman, Theodore C.

    2016-01-01

    Smoking continues to be the leading cause of preventable death in the USA, despite the vast and widely publicized knowledge about the negative health effects of tobacco smoking. Data show that smoking cessation is often accompanied by weight gain and an improvement in insulin sensitivity over time. However, paradoxically, post-cessation-related obesity might contribute to insulin resistance. Furthermore, post-cessation weight gain is reportedly the number one reason why smokers, especially women, fail to initiate smoking cessation or relapse after initiating smoking cessation. In this Review, we discuss the metabolic effects of stopping smoking and highlight future considerations for smoking cessation programs and therapies to be designed with an emphasis on reducing post-cessation weight gain. PMID:26939981

  19. Glucagon regulation of energy metabolism.

    PubMed

    Heppner, Kristy M; Habegger, Kirk M; Day, Jonathan; Pfluger, Paul T; Perez-Tilve, Diego; Ward, Brian; Gelfanov, Vasily; Woods, Steve C; DiMarchi, Richard; Tschöp, Matthias

    2010-07-14

    Glucagon has long been known as a counter-regulatory hormone to insulin of fundamental importance to glucose homeostasis. Its prominent ability to stimulate glycogenolysis and gluconeogenesis, has historically cast this peptide as one hormone where the metabolic consequences of increasing blood glucose levels, especially in obesity, are viewed largely as being deleterious. This perspective may be changing in light of emerging data and reconsideration of historic studies, which suggest that glucagon has beneficial effects on body fat mass, food intake, and energy expenditure. In this review, we discuss the mechanisms of glucagon-mediated body weight regulation as well as possible novel therapeutic approaches in the treatment of obesity and glucose intolerance that may arise from these findings. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. PMID:20381509

  20. Humanoid Flight Metabolic Simulator Project

    NASA Technical Reports Server (NTRS)

    Ross, Stuart

    2015-01-01

    NASA's Evolvable Mars Campaign (EMC) has identified several areas of technology that will require significant improvements in terms of performance, capacity, and efficiency, in order to make a manned mission to Mars possible. These include crew vehicle Environmental Control and Life Support System (ECLSS), EVA suit Portable Life Support System (PLSS) and Information Systems, autonomous environmental monitoring, radiation exposure monitoring and protection, and vehicle thermal control systems (TCS). (MADMACS) in a Suit can be configured to simulate human metabolism, consuming crew resources (oxygen) in the process. In addition to providing support for testing Life Support on unmanned flights, MADMACS will also support testing of suit thermal controls, and monitor radiation exposure, body zone temperatures, moisture, and loads.

  1. Light and Stomatal Metabolism 1

    PubMed Central

    Rao, I. Madhusudana; Anderson, Louise E.

    1983-01-01

    New evidence is provided regarding the direct effect of light on stomatal opening in the epidermis of the pea (Pisum sativum L. var Little Marvel) leaf. Light modulates the activity of a number of key enzymes involved in stomatal metabolism. When isolated epidermal strips are illuminated, phosphoenolpyruvate carboxylase, NADP-malate dehydrogenase, and NADP-isocitrate dehydrogenase are activated; and aspartate aminotransferase is inactivated. Sulfhydryl compounds, dithiothreitol and glutathione, enhance stomatal opening in epidermal strips both in light or darkness while the sulfhydryl reagent N-ethylmaleimide inhibits, indicating the possible involvement of sulfhydryl groups in stomatal movements. Further, light treatment increases measureable thiol levels in the epidermis about 3-fold. These results suggest that light modulation of enzymes in the epidermis may play a significant role in the mechanism of stomatal movement. PMID:16662847

  2. The Cyanobacterial Clock and Metabolism

    PubMed Central

    Pattanayak, Gopal; Rust, Michael J.

    2014-01-01

    Cyanobacteria possess the simplest known circadian clock, which presents a unique opportunity to study how rhythms are generated and how input signals from the environment reset the clock time. The kaiABC locus forms the core of the oscillator, and the remarkable ability to reconstitute oscillations using purified KaiABC proteins has allowed researchers to study mechanism using the tools of quantitative biochemistry. Autotrophic cyanobacteria experience major shifts in metabolism following a light-dark transition, and recent work suggests that input mechanisms that couple the day-night cycle to the clock involve energy and redox metabolites acting directly on clock proteins. We offer a summary of the current state of knowledge in this system and present a perspective for future lines of investigation. PMID:24667330

  3. Mammalian aquaglyceroporin function in metabolism.

    PubMed

    Laforenza, Umberto; Bottino, Cinzia; Gastaldi, Giulia

    2016-01-01

    Aquaglyceroporins are integral membrane proteins that are permeable to glycerol as well as water. The movement of glycerol from a tissue/organ to the plasma and vice versa requires the presence of different aquaglyceroporins that can regulate the entrance or the exit of glycerol across the plasma membrane. Actually, different aquaglyceroporins have been discovered in the adipose tissue, small intestine, liver, kidney, heart, skeletal muscle, endocrine pancreas and capillary endothelium, and their differential expression could be related to obesity and the type 2 diabetes. Here we describe the expression and function of different aquaglyceroporins in physiological condition and in obesity and type 2 diabetes, suggesting they are potential therapeutic targets for metabolic disorders. PMID:26456554

  4. Nutritional Aspect of Tryptophan Metabolism

    PubMed Central

    Fukuwatari, Tsutomu; Shibata, Katsumi

    2013-01-01

    Mammals, including humans, can synthesize the vitamin nicotinamide from tryptophan in the liver. The resultant nicotinamide is distributed to non-hepatic tissues. We have studied the effects of changes in tryptophan–nicotinamide metabolism on niacin nutritional status. The liver plays a critical role in nicotinamide supply. Animal studies showed that the tryptophan–nicotinamide pathway is affected by physiological conditions, the presence of disease, nutrients, hormones, and chemicals. Human studies have shown that 1 mg of nicotinamide is produced from 67 mg of tryptophan intake, and that the conversion ratio of tryptophan to nicotinamide is enhanced from mid to late pregnancy. These findings have contributed to the determination of dietary reference intakes for niacin recommended in the Dietary Reference Intakes for Japanese 2010. Our findings suggest that the conversion of nicotinamide from tryptophan is important in maintaining niacin nutrition. PMID:23922498

  5. Iron metabolism in mammalian cells.

    PubMed

    Walker, B L; Tiong, J W; Jefferies, W A

    2001-01-01

    Most living things require iron to exist. Iron has many functions within cells but is rarely found unbound because of its propensity to catalyze the formation of toxic free radicals. Thus the regulation of iron requirements by cells and the acquisition and uptake of iron into tissues in multicellular organisms is tightly regulated. In humans, understanding iron transport and utility has recently been advanced by a "great conjunction" of molecular genetics in simple organisms, identifying genes involved in genetic diseases of metal metabolism and by the application of traditional cell physiology approaches. We are now able to approach a rudimentary understanding of the "iron cycle" within mammals. In the future, this information will be applied toward modulating the outcome of therapies designed to overcome diseases involving metals. PMID:11597005

  6. Circadian periodicity of tryptophan metabolism

    PubMed Central

    Rapoport, Morton I.; Beisel, William R.

    1968-01-01

    Rhythmicity of tryptophan metabolism via the kynurenine pathway has been demonstrated in man. Normal subjects given 3 g of tryptophan at 0900 hours excreted almost three times the quantity of kynurenine, kynurenic acid, and xanthurenic acid than did subjects given the same dose at 2100 hours. Other metabolites of the kynurenine pathway varied in the same fashion but with lesser magnitude. In contrast, indican, a tryptophan metabolite not in the kynurenine pathway, varied inversely with the other metabolites measured. The data suggest that the liver enzyme tryptophan pyrrolase has a circadian rhythm in man similar to that already described in mice in a previous study. Tryptophan tolerance tests in the future should be controlled relative to time of amino acid administration. PMID:5641628

  7. Metabolic Signatures of Bacterial Vaginosis

    PubMed Central

    Morgan, Martin T.; Fiedler, Tina L.; Djukovic, Danijel; Hoffman, Noah G.; Raftery, Daniel; Marrazzo, Jeanne M.

    2015-01-01

    ABSTRACT Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from Lactobacillus dominant to a microbiota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabolomics approach. We further validated important metabolites using samples from a second cohort of women and a different platform to measure metabolites. In the primary study, we compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyrosequencing and concentrations of bacteria by quantitative PCR. We detected 279 named biochemicals; levels of 62% of metabolites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV. Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV. Lactobacillus crispatus and Lactobacillus jensenii exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Several metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated with all four clinical criteria. BV has strong metabolic signatures across multiple metabolic pathways, and these signatures are associated with the presence and concentrations of particular bacteria. PMID:25873373

  8. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    PubMed Central

    Gylling, Helena; Simonen, Piia

    2015-01-01

    The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

  9. PCB metabolism by ectomycorrhizal fungi

    SciTech Connect

    Donnelly, P.K.; Fletcher, J.S.

    1995-04-01

    Since 1976 the use of polychlorinated biphenyls (PCBs) has been banned in the U.S. Prior to this, commercial mixtures (Aroclors) had been used extensively as an industrial lubricant because of their nonflammable, nonreactive properties. These same properties are responsible for their persistent in the environment where they bind to soil particles and resist biodegradation. Decontamination of PCB-laden soil is expensive with excavation followed by either storage or incineration as the primary means of remediation. The use of microorganisms for PCB bioremediation has been gaining popularity in the past few years. Bacteria and/or fungi isolated from environmental samples have been used to degrade PCBs under laboratory conditions, but in field trials they have not been as effective. The most common explanation for the poor performance of PCB-degrading organisms introduced at contaminated sites is that they do not compete well with the existing populations. Plant-ectomycorrhizal systems may overcome this problem. Introduction and cultivation of a known host plant at a contaminated site has the potential of providing a survival advantage for ectomycorrhizal fungi that normally colonize the roots of the introduced plant. Ectomycorrhizal fungi exist naturally in the soil and normally grow in association with the roots of a host plant in a mutualistic symbiotic relationship. Preliminary in vitro examination of this group of fungi for their ability to enzymatically degrade xenobiotics is very promising. In vivo studies have shown that some of these fungi have the ability to degrade chlorinated, aromatic compounds, such as 2,4-D and atrazine. The aspect of ectomycorrhizal metabolism was investigated further in the current study by determining the ability of 21 different fungi to metabolize 19 different PCB congeners with varying chlorine content and substitution patterns. 13 refs., 1 fig., 2 tabs.

  10. Leucine metabolism in stable cirrhosis.

    PubMed

    Mullen, K D; Denne, S C; McCullough, A J; Savin, S M; Bruno, D; Tavill, A S; Kalhan, S C

    1986-01-01

    Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 +/- 17.1 vs. 138.3 +/- 20.4 mumoles per liter, mean +/- S.D., p less than 0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 +/- 19.0 vs. 87.8 +/- 19.0 mumoles per kg X hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 +/- 2.5 vs. 12.7 +/- 3.1 mumoles per kg X hr, p less than 0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3089896

  11. Correlated FLIM and PLIM for cell metabolism

    NASA Astrophysics Data System (ADS)

    Rück, A.; Breymayer, J.; Kalinina, S.

    2016-03-01

    Correlated imaging of phosphorescence and fluorescence lifetime parameters of metabolic markers is a challenge for direct investigating mechanisms related to cell metabolism and oxygen tension. A large variety of clinical phenotypes is associated with mitochondrial defects accomplished with changes in cell metabolism. In many cases the hypoxic microenvironment of cancer cells shifts metabolism from oxidative phosphorylation (OXPHOS) to anaerobic or aerobic glycolysis, a process known as "Warburg" effect. Also during stem cell differentiation a switch in cell metabolism is observed. A defective mitochondrial function associated with hypoxia has been invoked in many complex disorders such as type 2 diabetes, Alzheimers disease, cardiac ischemia/reperfusion injury, tissue inflammation and cancer. Cellular responses to oxygen tension have been studied extensively, optical imaging techniques based on time correlated single photon counting (TCSPC) to detect the underlying metabolic mechanisms are therefore of prominent interest. They offer the possibility by inspecting fluorescence decay characteristics of intrinsic coenzymes to directly image metabolic pathways. Moreover oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescent probe. The combination of both fluorescence lifetime imaging (FLIM) of coenzymes like NADH and FAD and phosphorescence lifetime (PLIM) of phosphorescent dyes could provide valuable information about correlation of metabolic pathways and oxygen tension.

  12. Miniaturized, Portable Sensors Monitor Metabolic Health

    NASA Technical Reports Server (NTRS)

    2014-01-01

    In order to measure astronauts' metabolic rates in space, Glenn Research Center partnered with Case Western University and the Cleveland Clinic to develop the Portable Unit for Metabolic Analysis (PUMA). Cleveland-based Orbital Research licensed and then modified PUMA to help the US Navy assess pilot oxygen problems and is now designing a device that can be used in hospitals.

  13. High Blood Pressure and Metabolic Syndrome

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More High Blood Pressure and Metabolic Syndrome Updated:Aug 12,2014 Metabolic ... content was last reviewed on 08/04/2014. High Blood Pressure • Home • About High Blood Pressure (HBP) Introduction What ...

  14. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  15. Elements of the cellular metabolic structure

    PubMed Central

    De la Fuente, Ildefonso M.

    2015-01-01

    A large number of studies have demonstrated the existence of metabolic covalent modifications in different molecular structures, which are able to store biochemical information that is not encoded by DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by specific input stimuli. Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in covalent post-translational modulation, so that determined functional memory can be embedded in multiple stable molecular marks. The metabolic dynamics governed by Hopfield-type attractors (functional processes), as well as the enzymatic covalent modifications of specific molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell. PMID:25988183

  16. Bariatric surgery: the indications in metabolic disease.

    PubMed

    Neff, K J; le Roux, C W

    2014-01-01

    As well as the pronounced effect on body mass index (BMI), bariatric surgery is increasingly recognized as being associated with improvements in morbidity and mortality in a range of conditions, from airways disease to cancer. In metabolic disease, the impact of bariatric surgery is particularly obvious with marked improvements in glycemic control in patients with type 2 diabetes mellitus, to the point of effecting diabetes remission in some. Hypertension and dyslipidemia, key components of the metabolic syndrome, also respond to bariatric surgery. Despite the increasing evidence of benefit in metabolic disease, the major national guidelines for selecting candidates for bariatric surgery retain their emphasis on body weight. In these guidelines, a BMI ≥35 kg/m(2) is needed to indicate surgery, even in those with profound metabolic disturbance. The recent International Diabetes Federation guidelines have identified the need to reorientate our focus from BMI to metabolic disease. In this review, we examine the developing indications for the use of bariatric surgery in metabolic disease. We will focus on type 2 diabetes mellitus and the metabolic syndrome. Within this, we will outline the data for using bariatric surgery as metabolic surgery, including those with a BMI <35 kg/m(2). PMID:23838610

  17. Carotenoid Metabolism: the Biosynthesis, Regulation, and Beyond

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Carotenoids are indispensable to plants and play a critical role in human nutrition and health. Significant progress has been made in our understanding of carotenoid metabolism in plants. The metabolic pathway has been extensively studied, and the genes encoding nearly all of the biosynthetic enzyme...

  18. Optimization of Cardiac Metabolism in Heart Failure

    PubMed Central

    Nagoshi, Tomohisa; Yoshimura, Michihiro; Rosano, Giuseppe M. C; Lopaschuk, Gary D; Mochizuki, Seibu

    2011-01-01

    The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure. PMID:21933140

  19. An Advance Organizer for Teaching Bacterial Metabolism

    ERIC Educational Resources Information Center

    Barbosa, Heloiza R.; Marques, Marilis V.; Torres, Bayardo B.

    2005-01-01

    The metabolic versatility of bacteria is a source of learning difficulty for students in classical microbiology courses. To facilitate the learning process, the authors developed an advance organizer. It consists of a set of six diagrams of metabolic pathways describing the basic living requirements of several types of bacteria: energy, carbon…

  20. Towards a metabolic therapy of cancer?

    PubMed

    Chiu, Martina; Ottaviani, Laura; Bianchi, Massimiliano G; Franchi-Gazzola, Renata; Bussolati, Ovidio

    2012-12-01

    It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs. PMID:23762991

  1. Optimization of cardiac metabolism in heart failure.

    PubMed

    Nagoshi, Tomohisa; Yoshimura, Michihiro; Rosano, Giuseppe M C; Lopaschuk, Gary D; Mochizuki, Seibu

    2011-12-01

    The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure. PMID:21933140

  2. Regulation of metabolism in Caenorhabditis elegans longevity.

    PubMed

    Gallo, Marco; Riddle, Donald L

    2010-01-01

    The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC Biology identifying metabolic signatures for longevity suggests that amino-acid pools may be important in longevity. PMID:20156326

  3. Tracking the pathway of arsenic metabolism

    EPA Science Inventory

    Although the toxic and carcinogenic properties of arsenic have been recognized for centuries, only in the past few decades has research focused on understanding the metabolic fate of arsenic in humans and relating metabolism to adverse health effects. In humans, conversion of in...

  4. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  5. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  6. Evolutionary constraints permeate large metabolic networks

    PubMed Central

    Wagner, Andreas

    2009-01-01

    Background Metabolic networks show great evolutionary plasticity, because they can differ substantially even among closely related prokaryotes. Any one metabolic network can also effectively compensate for the blockage of individual reactions by rerouting metabolic flux through other pathways. These observations, together with the continual discovery of new microbial metabolic pathways and enzymes, raise the possibility that metabolic networks are only weakly constrained in changing their complement of enzymatic reactions. Results To ask whether this is the case, I characterized pairwise and higher-order associations in the co-occurrence of genes encoding metabolic enzymes in more than 200 completely sequenced representatives of prokaryotic genera. The majority of reactions show constrained evolution. Specifically, genes encoding most reactions tend to co-occur with genes encoding other reaction(s). Constrained reaction pairs occur in small sets whose number is substantially greater than expected by chance alone. Most such sets are associated with single biochemical pathways. The respective genes are not always tightly linked, which renders horizontal co-transfer of constrained reaction sets an unlikely sole cause for these patterns of association. Conclusion Even a limited number of available genomes suffices to show that metabolic network evolution is highly constrained by reaction combinations that are favored by natural selection. With increasing numbers of completely sequenced genomes, an evolutionary constraint-based approach may enable a detailed characterization of co-evolving metabolic modules. PMID:19747381

  7. Swimming Performance and Metabolism of Golden Shiners

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The swimming ability and metabolism of golden shiners, Notemigonus crysoleucas, was examined using swim tunnel respirometery. The oxygen consumption and tail beat frequencies at various swimming speeds, an estimation of the standard metabolic rate, and the critical swimming speed (Ucrit) was determ...

  8. In vitro metabolism of aromatic nitriles.

    PubMed

    Markus, B; Kwon, C H

    1994-12-01

    Studies on the metabolic fate of aromatic nitriles, in contrast to their aliphatic counterparts, have been minimal and the subject of controversy. The in vitro metabolic fate of several aromatic nitriles with varying substituents was investigated by using rat liver subcellular fractions, with a particular emphasis on the nitrile moiety. Benzonitriles and 4-cyanophenols underwent oxidative metabolism to produce ring-hydroxylated metabolites. On the other hand, 2-cyanophenol was resistant to metabolism. o-Tolunitrile was metabolized and produced o-cyanobenzyl alcohol and phthalide. Phthalide, however, was chemically derived from o-cyanobenzyl alcohol, the initial metabolite. 4-Nitrobenzonitrile was resistant to oxidation on the ring, but was readily reduced to the corresponding amine metabolite under both aerobic and anaerobic conditions. Nitroxynil (3-iodo-4-hydroxy-5-nitrobenzonitrile) was metabolized to produce 3-iodo-4-hydroxy-5-nitrobenzamide and 3-iodo-4-hydroxy-5-nitrobenzoic acid. The enzyme(s) responsible for this hydrolytic metabolism was primarily localized in the cytosol. Among the nitriles tested, o-tolunitrile and nitroxynil produced metabolites in which the nitrile moiety was modified. Nitroxynil, however, was the only compound that was directly metabolized on the nitrile moiety by the rat liver enzyme(s). PMID:7891302

  9. VITAMIN D AND THE METABOLIC SYNDROME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The identification of vitamin D receptor (VDR) expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been...

  10. Hydrogen metabolism of photosynthetic bacteria and algae

    SciTech Connect

    Kumazawa, S.; Mitsui, A.

    1982-01-01

    The metabolism, metabolic pathways and biochemistry of hydrogen in photosynthetic bacteria and algae are reviewed. Detailed information on the occurrence and measurement of hydrogenase activity is presented. Hydrogen production rates for different species of algae and bacteria are presented. 173 references, 1 figure, 7 tables.

  11. Textbook Errors & Misconceptions in Biology: Cell Metabolism.

    ERIC Educational Resources Information Center

    Storey, Richard D.

    1991-01-01

    The idea that errors and misconceptions in biology textbooks are often slow to be discovered and corrected is discussed. Selected errors, misconceptions, and topics of confusion about cell metabolism are described. Fermentation, respiration, Krebs cycle, pentose phosphate pathway, uniformity of catabolism, and metabolic pathways as models are…

  12. Metabolic influences on neuroendocrine regulation of reproduction

    PubMed Central

    Navarro, Víctor M.; Kaiser, Ursula B.

    2014-01-01

    Purpose of review Reproduction is a tightly regulated function in which many mechanisms contribute to ensure the survival of the species. Among those, due to the elevated energy requirements of reproduction, metabolic factors exert a pivotal role in the control of hypothalamic-pituitary-gonadal axis. Although this control may occur at multiple levels of the axis, the majority of interactions between metabolic and reproductive systems take place in the hypothalamus. In this article, we present an overview of the state-of-the-art knowledge regarding the metabolic regulation of reproduction at the central level. We aim to identify the neuroanatomical location where both functions interconnect by discussing the likelihood of each component of the neuronal hierarchical network controlling gonadotropin-releasing hormone release to be first-order responders to metabolic cues, especially the peripheral metabolic signals leptin, insulin, and ghrelin. Recent findings Latest evidence suggests that the primary action of leptin, insulin, and ghrelin to regulate reproduction is located upstream of the main central elicitors of gonadotropin release, Kiss1 and gonadotropin-releasing hormone neurons, and neuroanatomically separated from their metabolic action. Summary The study of the neuronal interactions between the mechanisms governing metabolism and reproduction offers the platform to overcome or treat a number of prevailing metabolic and/or reproductive conditions. PMID:23807606

  13. Chemical Approaches to Probe Metabolic Networks

    PubMed Central

    Medina-Cleghorn, Daniel; Nomura, Daniel K.

    2013-01-01

    One of the more provocative realizations that have come out of the genome sequencing projects is that organisms possess a large number of uncharacterized or poorly characterized enzymes. This finding belies the commonly held notion that our knowledge of cell metabolism is nearly complete, underscoring the vast landscape of unannotated metabolic and signaling networks that operate under normal physiological conditions, let alone in disease states where metabolic networks may be rewired, dysregulated, or altered to drive disease progression. Consequently, the functional annotation of enzymatic pathways represents a grand challenge for researchers in the post-genomic era. This review will highlight the chemical technologies that have been successfully used to characterize metabolism, and put forth some of the challenges we face as we expand our map of metabolic pathways. PMID:23296751

  14. Theoretical description of metabolism using queueing theory.

    PubMed

    Evstigneev, Vladyslav P; Holyavka, Marina G; Khrapatiy, Sergii V; Evstigneev, Maxim P

    2014-09-01

    A theoretical description of the process of metabolism has been developed on the basis of the Pachinko model (see Nicholson and Wilson in Nat Rev Drug Discov 2:668-676, 2003) and the queueing theory. The suggested approach relies on the probabilistic nature of the metabolic events and the Poisson distribution of the incoming flow of substrate molecules. The main focus of the work is an output flow of metabolites or the effectiveness of metabolism process. Two simplest models have been analyzed: short- and long-living complexes of the source molecules with a metabolizing point (Hole) without queuing. It has been concluded that the approach based on queueing theory enables a very broad range of metabolic events to be described theoretically from a single probabilistic point of view. PMID:25142745

  15. Supply–demand balance and metabolic scaling

    PubMed Central

    Banavar, Jayanth R.; Damuth, John; Maritan, Amos; Rinaldo, Andrea

    2002-01-01

    It is widely accepted that metabolic rates scale across species approximately as the 3/4 power of mass in most if not all groups of organisms. Metabolic demand per unit mass thus decreases as body mass increases. Metabolic rates reflect both the ability of the organism's transport system to deliver metabolites to the tissues and the rate at which the tissues use them. We show that the ubiquitous 3/4 power law for interspecific metabolic scaling arises from simple, general geometric properties of transportation networks constrained to function in biological organisms. The 3/4 exponent and other observed scaling relationships follow when mass-specific metabolic demands match the changing delivery capacities of the network at different body sizes. Deviation from the 3/4 exponent suggests either inefficiency or compensating physiological mechanisms. Our conclusions are based on general arguments incorporating the minimum of biological detail and should therefore apply to the widest range of organisms. PMID:12149461

  16. Targeting T cell metabolism for therapy

    PubMed Central

    O’Sullivan, David

    2015-01-01

    In the past several years, a wealth of evidence has emerged illustrating how metabolism supports many aspects of T cell biology, as well as how metabolic changes drive T cell differentiation and fate. Here we outline developing principles in the regulation of T cell metabolism, and discuss how these processes are impacted in settings of inflammation and cancer. In this context we discuss how metabolic pathways might be manipulated for the treatment of human disease, including how metabolism may be targeted to prevent T cell dysfunction in inhospitable microenvironments, to generate more effective adoptive cellular immunotherapies in cancer, and to direct T cell differentiation and function towards non-pathogenic phenotypes in settings of autoimmunity. PMID:25601541

  17. Viscosity dictates metabolic activity of Vibrio ruber

    PubMed Central

    Borić, Maja; Danevčič, Tjaša; Stopar, David

    2012-01-01

    Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase (GPD) increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment. PMID:22826705

  18. Metabolically healthy obesity--does it exist?

    PubMed

    Boonchaya-anant, Patchaya; Apovian, Caroline M

    2014-10-01

    The prevalence of obesity has been increasing worldwide over the past 30 years and is a major public health concern. Obesity is known to be associated with metabolic disturbances including insulin resistance and inflammation; however, there is a subset of obese subjects who have normal metabolic profiles, and they have been identified as the metabolically healthy obese (MHO). Several studies have described MHO as obese individuals who have high levels of insulin sensitivity and the absence of diabetes, dyslipidemia, or hypertension. The prevalence of MHO varies from 20 to 30% among obese individuals. This review will discuss the MHO phenotype; the differences between MHO and metabolically unhealthy obese (MUO) individuals; and the possible underlying mechanisms including adipocyte differentiation, immune regulation, and cellular energy metabolism. PMID:25092577

  19. Engineering the Escherichia coli Fermentative Metabolism

    NASA Astrophysics Data System (ADS)

    Orencio-Trejo, M.; Utrilla, J.; Fernández-Sandoval, M. T.; Huerta-Beristain, G.; Gosset, G.; Martinez, A.

    Fermentative metabolism constitutes a fundamental cellular capacity for industrial biocatalysis. Escherichia coli is an important microorganism in the field of metabolic engineering for its well-known molecular characteristics and its rapid growth. It can adapt to different growth conditions and is able to grow in the presence or absence of oxygen. Through the use of metabolic pathway engineering and bioprocessing techniques, it is possible to explore the fundamental cellular properties and to exploit its capacity to be applied as industrial biocatalysts to produce a wide array of chemicals. The objective of this chapter is to review the metabolic engineering efforts carried out with E. coli by manipulating the central carbon metabolism and fermentative pathways to obtain strains that produce metabolites with high titers, such as ethanol, alanine, lactate and succinate.

  20. Imaging tumor metabolism using positron emission tomography.

    PubMed

    Lewis, David Y; Soloviev, Dmitry; Brindle, Kevin M

    2015-01-01

    Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabeled PET substrates can be traced at subphysiological concentrations, allowing noninvasive imaging of metabolism and intratumoral heterogeneity in systems ranging from advanced cancer models to patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of the tumor, including carbohydrate, amino acid, and fatty acid metabolism. In this review, we briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism are considered alongside new technical developments, such as combined PET/magnetic resonance imaging scanners, which could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine. PMID:25815854

  1. Heart Failure and Loss of Metabolic Control

    PubMed Central

    Wang, Zhao V.; Li, Dan L.; Hill, Joseph A.

    2014-01-01

    Heart failure is a leading cause of morbidity and mortality worldwide, currently affecting 5 million Americans. A syndrome defined on clinical terms, heart failure is the end-result of events occurring in multiple heart diseases, including hypertension, myocardial infarction, genetic mutations and diabetes, and metabolic dysregulation is a hallmark feature. Mounting evidence from clinical and preclinical studies suggests strongly that fatty acid uptake and oxidation are adversely affected, especially in end-stage heart failure. Moreover, metabolic flexibility, the heart’s ability to move freely among diverse energy substrates, is impaired in heart failure. Indeed, impairment of the heart’s ability to adapt to its metabolic milieu, and associated metabolic derangement, are important contributing factors in heart failure pathogenesis. Elucidation of molecular mechanisms governing metabolic control in heart failure will provide critical insights into disease initiation and progression, raising the prospect of advances with clinical relevance. PMID:24336014

  2. microRNAs and cholesterol metabolism

    PubMed Central

    Moore, Kathryn J.; Rayner, Katey J.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2010-01-01

    Cholesterol metabolism is tightly regulated at the cellular level. In addition to classic transcriptional regulation of cholesterol metabolism (e.g., by SREBP and LXR), members of a class of non-coding RNAs termed microRNAs (miRNAs) have recently been identified to be potent post-transcriptional regulators of lipid metabolism genes, including cholesterol homeostasis. We and others have recently shown that miR-33 regulates cholesterol efflux and HDL biogenesis by downregulating the expression of the ABC transporters, ABCA1 and ABCG1. In addition to miR-33, miR-122 and miR-370 have been shown to play important roles in regulating cholesterol and fatty acid metabolism. These new data suggest important roles of microRNAs in the epigenetic regulation of cholesterol metabolism and have opened new avenues for the treatment of dyslipidemias. PMID:20880716

  3. Metabolic regulation of stem cell function.

    PubMed

    Burgess, R J; Agathocleous, M; Morrison, S J

    2014-07-01

    Stem cell function is regulated by intrinsic mechanisms, such as transcriptional and epigenetic regulators, as well as extrinsic mechanisms, such as short-range signals from the niche and long-range humoral signals. Interactions between these regulatory mechanisms and cellular metabolism are just beginning to be identified. In multiple systems, differentiation is accompanied by changes in glycolysis, oxidative phosphorylation and the levels of reactive oxygen species. Indeed, metabolic pathways regulate proliferation and differentiation by regulating energy production and the generation of substrates for biosynthetic pathways. Some metabolic pathways appear to function differently in stem cells as compared with restricted progenitors and differentiated cells. They also appear to influence stem cell function by regulating signal transduction, epigenetic marks and oxidative stress. Studies to date illustrate the importance of metabolism in the regulation of stem cell function and suggest complex cross-regulation likely exists between metabolism and other stem cell regulatory mechanisms. PMID:24697828

  4. [Abnormality in bone metabolism after burn].

    PubMed

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  5. 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.

  6. [Ischemic myocardial metabolism and antianginal drugs].

    PubMed

    Ichihara, K

    1986-12-01

    The effect of several kinds of antianginal drugs: nitrates, coronary vasodilators, beta-adrenergic blocking agents and calcium entry blocking agents on the myocardial metabolism and myocardial acidosis during ischemia was studied in the dog heart in vivo. Ischemia was induced by ligating the left anterior descending coronary artery. Ischemia accelerated anaerobic metabolism in the myocardium, in which glycogen breakdown, accumulation of glycolytic intermediates, loss of high energy phosphate and tissue acidosis occurred. Nitroglycerin, beta-adrenergic blocking agents such as propranolol, and some calcium entry blocking agents such as diltiazem and flunarizine prevented the myocardial metabolism from shifting to an anaerobic metabolism in spite of ischemia. However, coronary vasodilators and the dihydropyridine type of calcium entry blocking agents were not capable of reducing changes in the myocardial metabolism and myocardial acidosis during ischemia. The author makes a point in the present review that all the drugs which dilate coronary artery are not always effective on the ischemic myocardium. PMID:3549484

  7. 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

  8. New research developments and insights from Metabolism

    PubMed Central

    Farr, Olivia M.; Camp, Michelle; Mantzoros, Christos S.

    2015-01-01

    In a field of great importance to daily life and clinical care, metabolic-related research covers a wealth of information and knowledge. This broad field encompasses a number of physical states that are increasingly critical to study, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Additionally, the impacts of diet, nutrition, and exercise on these physical states are an area of ever-important and expanding research. With the latest advances in metabolic research, much knowledge has been gained. Here, we present the newest findings from research published in Metabolism. We hope that these results provide not only critical knowledge needed for clinical care and daily life, but also a platform for the continuing expansion of research into metabolic-related issues. PMID:25549908

  9. Dynamic metabolic models in context: biomass backtracking.

    PubMed

    Tummler, Katja; Kühn, Clemens; Klipp, Edda

    2015-08-01

    Mathematical modeling has proven to be a powerful tool to understand and predict functional and regulatory properties of metabolic processes. High accuracy dynamic modeling of individual pathways is thereby opposed by simplified but genome scale constraint based approaches. A method that links these two powerful techniques would greatly enhance predictive power but is so far lacking. We present biomass backtracking, a workflow that integrates the cellular context in existing dynamic metabolic models via stoichiometrically exact drain reactions based on a genome scale metabolic model. With comprehensive examples, for different species and environmental contexts, we show the importance and scope of applications and highlight the improvement compared to common boundary formulations in existing metabolic models. Our method allows for the contextualization of dynamic metabolic models based on all available information. We anticipate this to greatly increase their accuracy and predictive power for basic research and also for drug development and industrial applications. PMID:26189715

  10. Macromolecular crowding explains overflow metabolism in cells

    PubMed Central

    Vazquez, Alexei; Oltvai, Zoltán N.

    2016-01-01

    Overflow metabolism is a metabolic phenotype of cells characterized by mixed oxidative phosphorylation (OxPhos) and fermentative glycolysis in the presence of oxygen. Recently, it was proposed that a combination of a protein allocation constraint and a higher proteome fraction cost of energy generation by OxPhos relative to fermentation form the basis of overflow metabolism in the bacterium, Escherichia coli. However, we argue that the existence of a maximum or optimal macromolecular density is another essential requirement. Here we re-evaluate our previous theory of overflow metabolism based on molecular crowding following the proteomic fractions formulation. We show that molecular crowding is a key factor in explaining the switch from OxPhos to overflow metabolism. PMID:27484619

  11. An online system for metabolic network analysis

    PubMed Central

    Cicek, Abdullah Ercument; Qi, Xinjian; Cakmak, Ali; Johnson, Stephen R.; Han, Xu; Alshalwi, Sami; Ozsoyoglu, Zehra Meral; Ozsoyoglu, Gultekin

    2014-01-01

    Metabolic networks have become one of the centers of attention in life sciences research with the advancements in the metabolomics field. A vast array of studies analyzes metabolites and their interrelations to seek explanations for various biological questions, and numerous genome-scale metabolic networks have been assembled to serve for this purpose. The increasing focus on this topic comes with the need for software systems that store, query, browse, analyze and visualize metabolic networks. PathCase Metabolomics Analysis Workbench (PathCaseMAW) is built, released and runs on a manually created generic mammalian metabolic network. The PathCaseMAW system provides a database-enabled framework and Web-based computational tools for browsing, querying, analyzing and visualizing stored metabolic networks. PathCaseMAW editor, with its user-friendly interface, can be used to create a new metabolic network and/or update an existing metabolic network. The network can also be created from an existing genome-scale reconstructed network using the PathCaseMAW SBML parser. The metabolic network can be accessed through a Web interface or an iPad application. For metabolomics analysis, steady-state metabolic network dynamics analysis (SMDA) algorithm is implemented and integrated with the system. SMDA tool is accessible through both the Web-based interface and the iPad application for metabolomics analysis based on a metabolic profile. PathCaseMAW is a comprehensive system with various data input and data access subsystems. It is easy to work with by design, and is a promising tool for metabolomics research and for educational purposes. Database URL: http://nashua.case.edu/PathwaysMAW/Web PMID:25267793

  12. Temporal Expression-based Analysis of Metabolism

    PubMed Central

    Segrè, Daniel

    2012-01-01

    Metabolic flux is frequently rerouted through cellular metabolism in response to dynamic changes in the intra- and extra-cellular environment. Capturing the mechanisms underlying these metabolic transitions in quantitative and predictive models is a prominent challenge in systems biology. Progress in this regard has been made by integrating high-throughput gene expression data into genome-scale stoichiometric models of metabolism. Here, we extend previous approaches to perform a Temporal Expression-based Analysis of Metabolism (TEAM). We apply TEAM to understanding the complex metabolic dynamics of the respiratorily versatile bacterium Shewanella oneidensis grown under aerobic, lactate-limited conditions. TEAM predicts temporal metabolic flux distributions using time-series gene expression data. Increased predictive power is achieved by supplementing these data with a large reference compendium of gene expression, which allows us to take into account the unique character of the distribution of expression of each individual gene. We further propose a straightforward method for studying the sensitivity of TEAM to changes in its fundamental free threshold parameter θ, and reveal that discrete zones of distinct metabolic behavior arise as this parameter is changed. By comparing the qualitative characteristics of these zones to additional experimental data, we are able to constrain the range of θ to a small, well-defined interval. In parallel, the sensitivity analysis reveals the inherently difficult nature of dynamic metabolic flux modeling: small errors early in the simulation propagate to relatively large changes later in the simulation. We expect that handling such “history-dependent” sensitivities will be a major challenge in the future development of dynamic metabolic-modeling techniques. PMID:23209390

  13. Metabolic Dependencies in RAS-Driven Cancers.

    PubMed

    Kimmelman, Alec C

    2015-04-15

    The ability to inhibit the RAS oncogene has been the holy grail of oncology because of the critical role of this gene in a multitude of tumor types. In addition, RAS-mutant tumors are among the most aggressive and refractory to treatment. Although directly targeting the RAS oncogene has proven challenging, an alternative approach for treating RAS-driven cancers is to inhibit critical downstream events that are required for tumor maintenance. Indeed, much focus has been put on inhibiting signaling cascades downstream of RAS. Recent studies have shown that oncogenic RAS promotes a metabolic reprogramming of tumor cells, shifting them toward an anabolic metabolism necessary to produce biomass to support unconstrained proliferation. These cancers also use a diverse set of fuel sources to meet their metabolic needs and have even developed a variety of mechanisms to act as metabolic scavengers to obtain necessary metabolic substrates from both extracellular and intracellular sources. Collectively, these adaptations can create "metabolic bottlenecks" whereby tumor cells rely on particular pathways or rate-limiting metabolites. In this regard, inhibiting individual or combinations of these metabolic pathways can attenuate growth in preclinical models. Because these dependencies are tumor selective and downstream of oncogenic RAS, there is the opportunity for therapeutic intervention. Although targeting tumor metabolism is still in the early days of translation to patients, our continued advances in understanding critical metabolic adaptations in RAS-driven cancers, as well as the ability to study this altered metabolism in relevant tumor models, will accelerate the development of new therapeutic approaches. Clin Cancer Res; 21(8); 1828-34. ©2015 AACR. See all articles in this CCR Focus section, "Targeting RAS-Driven Cancers." PMID:25878364

  14. Precision Metabolic Engineering: the Design of Responsive, Selective, and Controllable Metabolic Systems

    PubMed Central

    McNerney, Monica P.; Watstein, Daniel M.; Styczynski, Mark P.

    2015-01-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed “precision metabolic engineering,” involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. PMID:26189665

  15. Chemical Reporter for Visualizing Metabolic Cross-Talk between Carbohydrate Metabolism and Protein Modification

    PubMed Central

    2015-01-01

    Metabolic chemical reporters have been largely used to study posttranslational modifications. Generally, it was assumed that these reporters entered one biosynthetic pathway, resulting in labeling of one type of modification. However, because they are metabolized by cells before their addition onto proteins, metabolic chemical reporters potentially provide a unique opportunity to read-out on both modifications of interest and cellular metabolism. We report here the development of a metabolic chemical reporter 1-deoxy-N-pentynyl glucosamine (1-deoxy-GlcNAlk). This small-molecule cannot be incorporated into glycans; however, treatment of mammalian cells results in labeling of a variety proteins and enables their visualization and identification. Competition of this labeling with sodium acetate and an acetyltransferase inhibitor suggests that 1-deoxy-GlcNAlk can enter the protein acetylation pathway. These results demonstrate that metabolic chemical reporters have the potential to isolate and potentially discover cross-talk between metabolic pathways in living cells. PMID:25062036

  16. Metabolic correlates of learning disability.

    PubMed

    Nyhan, W L; Wulfeck, B B; Tallal, P; Marsden, D L

    1989-01-01

    To summarize, the neuropsychologic findings in MSUD and MMA children in both groups demonstrated deficits in cognitive/language areas, but interesting individual differences existed. For example, a marked contrast in abilities existed between NT and GV, even taking into account the age difference between these children with MSUD. While NT's general intellectual functioning was within the low-average range, GV was severely impaired. In more specific areas of cognitive functioning, NT had an uneven performance profile with areas of strengths and weaknesses, while GV evidenced a flat profile with significant impairment in all areas. NT demonstrated mild delay in visual-spatial processing, articulation development, motor-speech abilities, and selective attention and concentration; however, his language and psychosocial development were within the broad range of normality. In contrast, GV exhibited severe dysfunction in speech, language, and perceptual/conceptual development. The three children with MMA also exhibited a range of disabilities in cognitive functioning. TJ and SH contrasted in the degree of developmental delay across language and cognitive domains. Both were distractible and exhibited very short attention spans but there was a measurable difference in the extent of their speech, language, visual-spatial development. CH was markedly delayed in all areas of cognitive development, which is consistent with global retardation. The severity of her disease and its probable impact on brain development were undoubtedly related to her intellectual impairment. These datasets illustrate the challenges we face, because within each group we see a range of impairment. Nevertheless, we are optimistic that our efforts to relate metabolic, anatomic and neuropsychologic findings for such children will lead to a better understanding of these disorders. We are hopeful that this will result in new advances in diagnosis and intervention, which will ultimately improve the

  17. Filamentation of Metabolic Enzymes in Saccharomyces cerevisiae.

    PubMed

    Shen, Qing-Ji; Kassim, Hakimi; Huang, Yong; Li, Hui; Zhang, Jing; Li, Guang; Wang, Peng-Ye; Yan, Jun; Ye, Fangfu; Liu, Ji-Long

    2016-06-20

    Compartmentation via filamentation has recently emerged as a novel mechanism for metabolic regulation. In order to identify filament-forming metabolic enzymes systematically, we performed a genome-wide screening of all strains available from an open reading frame-GFP collection in Saccharomyces cerevisiae. We discovered nine novel filament-forming proteins and also confirmed those identified previously. From the 4159 strains, we found 23 proteins, mostly metabolic enzymes, which are capable of forming filaments in vivo. In silico protein-protein interaction analysis suggests that these filament-forming proteins can be clustered into several groups, including translational initiation machinery and glucose and nitrogen metabolic pathways. Using glutamine-utilising enzymes as examples, we found that the culture conditions affect the occurrence and length of the metabolic filaments. Furthermore, we found that two CTP synthases (Ura7p and Ura8p) and two asparagine synthetases (Asn1p and Asn2p) form filaments both in the cytoplasm and in the nucleus. Live imaging analyses suggest that metabolic filaments undergo sub-diffusion. Taken together, our genome-wide screening identifies additional filament-forming proteins in S. cerevisiae and suggests that filamentation of metabolic enzymes is more general than currently appreciated. PMID:27312010

  18. Hearing Loss, Dizziness, and Carbohydrate Metabolism

    PubMed Central

    Albernaz, Pedro L. Mangabeira

    2015-01-01

    Introduction  Metabolic activity of the inner ear is very intense, and makes it sensitive to changes in the body homeostasis. This study involves a group of patients with inner ear disorders related to carbohydrate metabolism disturbances, including hearing loss, tinnitus, dizziness, and episodes of vertigo. Objectives  To describe the symptoms of metabolic inner ear disorders and the examinations required to establish diagnoses. These symptoms are often the first to allow for an early diagnosis of metabolic disorders and diabetes. Methods  Retrospective study of 376 patients with inner ear symptoms suggestive of disturbances of carbohydrate metabolism. The authors present patientś clinical symptoms and clinical evaluations, with emphasis on the glucose and insulin essays. Results  Authors based their conclusions on otolaryngological findings, diagnostic procedures and treatment principles. They found that auditory and vestibular symptoms usually occur prior to other manifestations of metabolic changes, leading to an early diagnosis of hyperinsulinemia, intestinal sugar malabsorption or diabetes. Previously undiagnosed diabetes mellitus type II was found in 39 patients. Conclusions  The identification of carbohydrate metabolism disturbances is important not only to minimize the patients' clinical symptoms, but also to help maintain their general health. PMID:27413410

  19. Molecular Interactions between NAFLD and Xenobiotic Metabolism

    PubMed Central

    Naik, Adviti; Belič, Aleš; Zanger, Ulrich M.; Rozman, Damjana

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterized by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity, and insulin resistance. The progression of NAFLD to non-alcoholic steatohepatitis and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signaling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD. PMID:23346097

  20. Optimal flux patterns in cellular metabolic networks

    SciTech Connect

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.