Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the unitrophic metabolism of acetate and methanol individually and the mixotrophic utilization of these compounds by using detailed (14)C-labeled tracer studies in a strain of Methanosarcina barkeri adapted to grow on acetate as the sole carbon and energy source. The substrate consumption rate and methane production rate were significantly lower on acetate alone than during the unitrophic or mixotrophic metabolism of methanol. Cell yields (in grams per mole of substrate) were identical during exponential growth on acetate and exponential growth on methanol. During unitrophic metabolism of acetate, the methyl moiety accounted for the majority of the CH(4) produced, but 14% of the CO(2) generated originated from the methyl moiety. This correlated with the concurrent reduction of equivalent amounts of the C-1 of acetate to CH(4). (14)CH(4) was also produced from added (14)CO(2), although to a lesser extent than from reduction of the C-1 of acetate. During mixotrophic metabolism, methanol and acetate were catabolized simultaneously. The rates of (14)CH(4) and (14)CO(2) generation from [2-(14)C]acetate were logarithmic and higher in mixotrophic than in unitrophic cultures at substrate concentrations of 50 mM. A comparison of the oxidoreductase activities in cell extracts of the acetate-adapted strain grown on acetate and of strain MS grown on methanol or on H(2) plus CO(2) indicated that the pyruvate, alpha-ketoglutarate, and isocitrate dehydrogenase activities remained constant, whereas the CO dehydrogenase activity was significantly higher (5,000 nmol/min per mg of protein) in the acetate-adapted strain. These results suggested that a significant intramolecular redox pathway is possible for the generation of CH(4) from acetate, that energy metabolism from acetate by M. barkeri is not catabolite repressed by methanol, and that the acetate-adapted strain is a metabolic mutant with derepressed CO dehydrogenase activity.
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PMID:Comparison of unitrophic and mixotrophic substrate metabolism by acetate-adapted strain of Methanosarcina barkeri. 679 21

Isozymes of 23 cultures of the anaerobic rumen fungi and seven cultures of aerobic chytridiomycete fungi were analysed by PAGE. A total of 14 isozyme loci were successfully typed by PAGE. They were peptidase A & C-1, peptidase A & C-2, peptidase D-1, peptidase D-2, malate dehydrogenase-1, malate dehydrogenase-2, esterase-1, esterase-2, malic enzyme-1, malic enzyme-2, isocitrate dehydrogenase, shikimate dehydrogenase, phosphoglucomutase and 6-phosphogluconate dehydrogenase. Isozyme analysis can be used for studying the genetic relationships among the different anaerobic rumen fungi and the aerobic chytridiomycete fungi and the isozyme characteristics can serve as additional taxonomic criteria in the classification of the anaerobic rumen fungi. A dendrogram based on the isozyme data demonstrated that the anaerobic rumen fungi formed a cluster, indicating a monophyletic group, distinctly separated from the aerobic chytridiomycete fungi. Piromyces communis and P. minutus showed a close relationship but P. spiralis showed a more distant relationship to both P. communis and P. minutus. Piromyces as a whole was more related to Caecomyces than to Neocallimastix. Orpinomyces was also found to be more related to Piromyces and Caecomyces than to Neocallimastix. Orpinomyces intercalaris C 70 from cattle showed large genetic variation from O. joyonii, indicating that it is a different species.
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PMID:Isozyme analysis of anaerobic rumen fungi and their relationship to aerobic chytrids. 808 8

Methylation of lysine-4 of histone H3 (H3K4men) is an important regulatory factor in eukaryotic transcription. Removal of the transcriptionally activating H3K4 methylation is catalyzed by histone demethylases, including the Jumonji C (JmjC) KDM5 subfamily. The JmjC KDMs are Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenases, some of which are associated with cancer. Altered levels of tricarboxylic acid (TCA) cycle intermediates and the associated metabolites D- and L-2-hydroxyglutarate (2HG) can cause changes in chromatin methylation status. We report comprehensive biochemical, structural and cellular studies on the interaction of TCA cycle intermediates with KDM5B, which is a current medicinal chemistry target for cancer. The tested TCA intermediates were poor or moderate KDM5B inhibitors, except for oxaloacetate and succinate, which were shown to compete for binding with 2OG. D- and L-2HG were moderate inhibitors at levels that might be relevant in cancer cells bearing isocitrate dehydrogenase mutations. Crystallographic analyses with succinate, fumarate, L-malate, oxaloacetate, pyruvate and D- and L-2HG support the kinetic studies showing competition with 2OG. An unexpected binding mode for oxaloacetate was observed in which it coordinates the active site metal via its C-4 carboxylate rather than the C-1 carboxylate/C-2 keto groups. Studies employing immunofluorescence antibody-based assays reveal no changes in H3K4me3 levels in cells ectopically overexpressing KDM5B in response to dosing with TCA cycle metabolite pro-drug esters, suggesting that the high levels of cellular 2OG may preclude inhibition. The combined results reveal the potential for KDM5B inhibition by TCA cycle intermediates, but suggest that in cells, such inhibition will normally be effectively competed by 2OG.
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PMID:Studies on the Interaction of the Histone Demethylase KDM5B with Tricarboxylic Acid Cycle Intermediates. 2882 49