Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the pH-independent role of bicarbonate on glutamine and glutamate metabolism. Changes in the concentration of key intermediates and products during the incubations were used to calculate metabolite flux rates through specific mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as substrates, bicarbonate caused an inhibition of glutamate oxalacetate transaminase flux and a stimulation of glutamate deamination. The same effects were also produced with addition of either aminooxyacetate or malonate. These effects of bicarbonate were prevented when 0.2 mM malate was included as an additional substrate. Bicarbonate ion was identified as a potent competitive inhibitor of rat kidney cortex succinate dehydrogenase. These results indicate that aminooxyacetate, malonate, and bicarbonate all act to stimulate glutamate deamination through a suppression of glutamate transamination, and that the control by transamination of glutamate deamination is due to alterations in alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with glutamine in the absence of glutamate, bicarbonate was found to inhibit glutamate dehydrogenase flux. This effect was found to be due in part to the lower intramitochondrial pH observed in incubations with bicarbonate. These findings indicate that bicarbonate ion, independent of pH, may have an important regulatory role in renal glutamine and glutamate metabolism.
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PMID:Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria. 286 61

2-Keto-3-fluoroglutaric acid prepared by acid hydrolysis of its diethyl ester is stable, as the free acid in aqueous solution at pH 2, and can be stored at -20 degrees C for several years. Both enantiomers are reduced by NADH in the presence of glutamate dehydrogenase (EC 1.4.1.2) to the two diastereomers of 3-fluoro-L-glutamate, which are stable at neutral pH and at high pH unless heated. 2-Keto-3-fluoroglutarate exists in solution almost entirely as a hydrate both at low and neutral pH. Both enantiomers of ketofluoroglutarate react with the pyridoxamine forms of aspartate, alanine and 4-aminobutyrate transaminases to give fluoride release. 2 mol of cosubstrate amino acid react for each mol of ketofluoroglutarate (KFG) when starting from the pyridoxamine form of the enzyme: 2 RCHNH2COOH + KFG + H2O----F- + NH4+ + glutamate + 2 RCOCOOH. Both diastereomers of fluoroglutamate are decarboxylated by glutamate decarboxylase (EC 4.1.1.15) with fluoride release: KFG + H2O----CO2 + F- + HCOCH2CH2COOH. By contrast, only one isomer of fluoroglutamate will react with the pyridoxal form of glutamate-oxalacetate transaminase to give fluoride release: HOOCCHNH2CHFCH2COOH + H2O----4F- + NH4+ + HOOCCOCH2CH2COOH. The enzymatic decarboxylation of 3-fluoroisocitrate produces only one enantiomer of ketofluoroglutarate, which is reduced to threo (2R,3R)-3-fluoroglutamate by NADH and glutamate dehydrogenase: [2R,3S]-HOOCCH(OH)CF(COOH)CH2COOH + NADP+----[3R]-KFG + CO2 + NADPH + H+. The proton, 13C, and 19F-NMR parameters of ketofluoroglutarate and the two fluoroglutamate diastereomers are presented. These molecules are useful probes of enzymatic mechanisms thought to involve carbanion intermediates.
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PMID:2-Keto-3-fluoroglutarate: a useful mechanistic probe of 2-keto-glutarate-dependent enzyme systems. 289 78

Cell-free extracts of proteolytic strains of Clostridium botulinum types A, B and F (group I) were found to have unusually high specific activities of NAD+-dependent L-glutamate dehydrogenase (NAD-GDH). In comparison, nonproteolytic strains of types B, E and F (group II) had low specific activities. The enzyme was purified 131-fold from C. botulinum 113B to a final specific activity of greater than 1,092 mumol x min-1 x mg protein-1. The enzyme is a hexamer of a polypeptide of Mr = 42,500, and the native molecular weight is 250,800. The apparent Km values for substrates were 5.3 mM for glutamate and 0.028 mM for NAD+ in the deamination reaction, and 7.2 mM for alpha-ketoglutarate, 243 mM for NH4+ and 0.028 mM for NADH in the reverse reaction. NADP+ did not serve as a hydrogen acceptor for the enzyme. Activity in the animation direction was inhibited by fumarate, oxalacetate, aspartate, glutamate and glutamine. The results suggest that GDH is important in group I (proteolytic) C. botulinum to generate alpha-ketoglutarate as a substrate for transamination reactions. We have also found that the high activity decreases significantly when cells are exposed to sodium chloride. Therefore GDH probably has several important physiological roles in group I proteolytic C. botulinum.
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PMID:Purification, properties, and metabolic roles of NAD+-glutamate dehydrogenase in Clostridium botulinum 113B. 306 71

The net production of citrate from exogenous substrates by rat ventral prostate was investigated. The preparation of isolated prostate epithelial cells was described. These cells were capable of oxidizing pyruvate (5 mmol/l) as a source of acetyl coenzyme A. The addition of aspartate + alpha-ketoglutarate (5 mmol/l) in the presence of pyruvate resulted in significant net production of citrate and excess oxalacetate. In the presence of aspartate and glutamate, the cells were capable of producing citrate without excessive oxalacetate production. Neither glucose alone nor glucose plus pyruvate resulted in net citrate production. The results demonstrated that aspartate could serve as a 4-carbon source of oxalacetate for citrate synthesis. Furthermore, the results indicate the intramitochondrial operation of a glutamate-aspartate-citrate pathway involving mitochondrial aspartate aminotransferase and glutamic dehydrogenase activities in prostate epithelial cells.
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PMID:Net citrate production by isolated prostate epithelial cells. 337 41

The synthesis of citric and glutamic acids by extracts of Chloropseudomonas ethylicum was studied with labeled precursors. When acetyl-coenzyme A-1-(14)C was used as substrate, only 0.1% of the total radioactivity was found in the C-5 position of citric acid; whereas, with oxalacetate-4-(14)C as substrate, 100% of the total radioactivity was found in C-5. These results demonstrated that the Chloropseudomonas citrate synthetase had an absolute stereospecificity, identical to that of the pig heart synthetase. The distribution of radioactivity in the glutamic acid synthesized from acetyl-coenzyme A-1-(14)C was 0% in C-1 and 94.0% in C-5; whereas the glutamic acid formed from oxalacetate-4-(14)C contained 89.6% in C-1 and 0.5% in C-5. This distribution is entirely consistent with the biosynthesis of glutamic acid from citric acid via aconitase, d(s)-isocitrate, and l-glutamate dehydrogenases. The presence of l-glutamate dehydrogenase in extracts was demonstrated. The stereospecificity of the citrate synthetase and the pattern of glutamate labeling further establish that the aconitase of Chloropseudomonas is completely stereospecific.
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PMID:Stereospecificity of citrate synthetase in relation to glutamate biosynthesis by extracts of Chloropseudomonas ethylicum. 564 42

Glutamate dehydrogenase activity was determined in mitochondrial preparations from rat ventral prostate and rat kidney. Kinetic parameters of the ventral prostate enzyme were comparable to those for the kidney enzyme. Glutamate dehydrogenase activity in the direction of glutamate oxidative deamination was inhibited by alpha-ketoglutarate. However, the characteristics of alpha-ketoglutarate inhibition indicated that glutamate oxidation via glutamate dehydrogenase can occur at in vivo prostatic alpha-ketoglutarate levels. These results suggest that glutamate dehydrogenase activity in prostate may provide a continuous source of alpha-ketoglutarate for aspartate transamination to oxalacetate and ultimate citrate synthesis. In addition prostate mitochondria are able to couple the glutamic dehydrogenase reaction to aspartate aminotransferase. Under these conditions aspartate in the presence of glutamate and acetyl coenzyme A will result in a net synthesis of citrate. Consequently we propose an aspartate-glutamate pathway for citrate synthesis in prostate.
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PMID:Glutamate dehydrogenase and a proposed glutamate-aspartate pathway for citrate synthesis in rat ventral prostate. 615 Jan 22

To study the effect of an acute dose of ethanol on carbon tetrachloride (CCl4) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CCl4 (1.5 ml/kg body wt.). Three hours after acute CCl4 intoxication there was a striking increase in CCl4 concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P less than 0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CCl4 alone showed CCl4 concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CCl4 and ethanol when compared to those receiving CCl4 alone, showing that ethanol given intraperitoneally or intragastrically enhances CCl4 hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CCl4 concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CCl4, such as direct effects of ethanol on the CCl4 metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CCl4 hepatotoxicity by ethanol.
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PMID:Effect of ethanol on carbon tetrachloride levels and hepatotoxicity after acute carbon tetrachloride poisoning. 653 81

Peak levels of carbon tetrachloride (CCl4) as determined by head-space gas chromatography were observed 3-6 h following an acute oral dose of CCl4 in the blood, liver and fat of rats. Subsequently, there was a rapid decline of CCl4 levels. Conversely, serum activities of enzymes originating from the liver such as glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GDH) increased considerably and showed activity peaks between 12-48 h following CCl4 administration, indicating a delayed response of CCl4 on the activity levels of enzymes in the blood.
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PMID:Carbon tetrachloride (CCl4) levels and serum activities of liver enzymes following acute CCl4 intoxication. 662 3

14C-labeled bicarbonate was incorporated into trichloroacetic acid-insoluble material by cell suspensions of A. viscosus strain M100 and also into the four-carbon fermentation product, succinate, but not into the three-carbon fermentation product, lactate. The initial step in the conversion of 14C-labeled bicarbonate into both trichloroacetic acid-insoluble material and succinate was catalyzed by the enzyme phosphoenolypyruvate carboxylase, which served to convert the glycolytic intermediate, phosphoenolpyruvate, and bicarbonate to the four-carbon compound, oxalacetate. The metabolic fate of oxalacetate was its conversion to either trichloroacetic acid-insoluble material or succinate. One pathway by which oxalacetate may be metabolized into acid-insoluble material is via its conversion to the biosynthetic precursor aspartate by the action of glutamate aspartate aminotransferase. One source of the alpha-amino group of aspartate was the ammonium ion, which could be incorporated into glutamate, the substrate of the glutamate aspartate aminotransferase reaction, by the action of a reduced nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase whose reducing equivalents could be derived from the nicotinamide adenine dinucleotide phosphate-dependent oxidative reactions of the hexose monophosphate pathway catalyzed by glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Alternatively, oxalacetate was converted to the fermentation product, succinate, through the sequential action of malate dehydrogenase, fumarase, and succinic dehydrogenase. The resolution and partial purification of phosphoenolpyruvate carboxylase, glutamate aspartate aminotransferase, glutamate dehydrogenase, malate dehydrogenase, fumarase, and succinic dehydrogenase are also reported.
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PMID:Carbon dioxide metabolism by Actinomyces viscosus: pathways for succinate and aspartate production. 676 22

Experiments performed in polyethylene glycol and with a divalent crosslinker indicate that both mitochondrial malate dehydrogenase and aspartate aminotransferase can form hetero enzyme--enzyme complexes with either glutamate dehydrogenase or citrate synthase. In general, these as previous results indicate that complexes with the aminotransferase are favored over those with malate dehydrogenase and complexes with glutamate dehydrogenase are favored over those with citrate synthase. When the levels of enzymes are low, the only detectable complex is between the aminotransferase and glutamate dehydrogenase. Under these conditions, palmitoyl-CoA is required for complexes between the other three enzyme pairs, however, palmitoyl-CoA also enhances interactions between glutamate dehydrogenase and the aminotransferase. DPNH disrupts complexes with malate dehydrogenase and has little effect on those with the aminotransferase, while oxalacetate disrupts complexes with citrate synthase but has little effect on those with glutamate dehydrogenase. The citrate synthase-aminotransferase complex was favored in the presence of DPNH plus malate, which disrupt the other three enzyme-enzyme complexes. Glutamate dehydrogenase has a higher affinity and capacity than citrate synthase for palmitoyl-CoA. Consequently, lower levels of palmitoyl-CoA are required to enhance interactions with glutamate dehydrogenase. Furthermore, glutamate dehydrogenase can compete with citrate synthase for palmitoyl-CoA and thus can prevent palmitoyl-CoA from enhancing interactions between citrate synthase and either malate dehydrogenase or the aminotransferase.
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PMID:Complexes between mitochondrial enzymes and either citrate synthase or glutamate dehydrogenase. 682 31


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