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)

1. Changes in the concentrations of ammonia, glutamine, glutamate, 2-oxoglutarate, 3-hydroxybutyrate, acetoacetate, alanine, aspartate, malate, lactate, pyruvate, NAD(+), NADH and adenine nucleotides were measured in freeze-clamped rat liver during ischaemia. 2. Although the concentrations of most of the metabolites changed rapidly during ischaemia the ratios [glutamate]/[2-oxoglutarate][NH(4) (+)] and [3-hydroxybutyrate]/[acetoacetate] changed equally and the value of the expression [3-hydroxybutyrate][2-oxoglutarate][NH(4) (+)]/[acetoacetate][glutamate] remained approximately constant, indicating that the 3-hydroxybutyrate dehydrogenase and glutamate dehydrogenase systems were at near-equilibrium with the mitochondrial NAD(+) couple. 3. The value of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] was about 0.7 in vivo and remained fairly constant during the ischaemic period of 5min, although the concentrations of alanine and oxoglutarate changed substantially. No explanation can be offered why the value of the ratio differed from that of the equilibrium constant of the alanine aminotransferase reaction, which is 1.48. 4. Injection of l-cycloserine 60min before the rats were killed increased the concentration of alanine in the liver fourfold and decreased the concentration of the other metabolites measured, except that of pyruvate. During ischaemia the concentration of alanine did not change but that of aspartate almost doubled. 5. After treatment with l-cycloserine the value in vivo of the expression [alanine][oxoglutarate]/[pyruvate][glutamate] rose from 0.7 to 2.4. During ischaemia the value returned to 0.8. 6. The effects of l-cycloserine are consistent with the assumption that it specifically inhibits alanine aminotransferase. 7. Most of the alanine formed during ischaemia is probably derived from pyruvate and from ammonia released by the deamination of adenine nucleotides and glutamine. The alanine is presumably formed by the combined action of glutamate dehydrogenase and alanine aminotransferase. 8. The rate of anaerobic glycolysis, calculated from the increase in the lactate concentration, was 1.3mumol/min per g fresh wt. 9. Although the concentrations of the adenine nucleotides changed rapidly during ischaemia, the ratio [ATP][AMP]/[ADP](2) remained constant at 0.54, indicating that adenylate kinase established near-equilibrium under these conditions.
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PMID:Effects of ischaemia on metabolite concentrations in rat liver. 431 90

The effect of cAMP on the intracellular levels of five enzymes concerned with the interconversion of glutamate and glutamine in E. coli has been examined. Cyclic AMP added to the culture medium increases the levels of glutamate dehydrogenase (EC 1.4.1.4) and glutamine synthetase (EC 6.3.1.2); it decreases the levels of glutamate synthase (EC 1.4.1.X), and glutaminase A (EC 3.5.1.2). Cyclic AMP did not affect the level of glutaminase B (EC 3.5.1.2). These alterations in enzyme levels by cAMP require cyclic AMP receptor protein, since the levels of these enzymes were unchanged by cAMP in a mutant lacking this receptor. Chloramphenicol also abolished the effects of cAMP, a result that implies protein synthesis is necessary for these changes in enzyme levels to occur. The reciprocal effects of cAMP on the levels of these enzymes may play an important role in the cellular regulation of nitrogen metabolism.
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PMID:Adenosine 3':5'-cyclic monophosphate control of the enzymes of glutamine metabolism in Escherichia coli. 440 45

1. In epididymal adipose tissue synthesizing fatty acids from fructose in vitro, addition of insulin led to a moderate increase in fructose uptake, to a considerable increase in the flow of fructose carbon atoms to fatty acid, to a decrease in the steady-state concentration of lactate and pyruvate in the medium, and to net uptake of lactate and pyruvate from the medium. It is concluded that insulin accelerates a step in the span pyruvate-->fatty acid. 2. Mitochondria prepared from fat-cells exposed to insulin put out more citrate than non-insulin-treated controls under conditions where the oxaloacetate moiety of citrate was formed from pyruvate by pyruvate carboxylase and under conditions where it was formed from malate. This suggested that insulin treatment of fat-cells led to persistent activation of pyruvate dehydrogenase. 3. Insulin treatment of epididymal fat-pads in vitro increased the activity of pyruvate dehydrogenase measured in extracts of the tissue even in the absence of added substrate; the activities of pyruvate carboxylase, citrate synthase, glutamate dehydrogenase, acetyl-CoA carboxylase, NADP-malate dehydrogenase and NAD-malate dehydrogenase were not changed by insulin. 4. The effect of insulin on pyruvate dehydrogenase activity was inhibited by adrenaline, adrenocorticotrophic hormone and dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate). The effect of insulin was not reproduced by prostaglandin E(1), which like insulin may lower the tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate) and inhibit lipolysis. 5. Adipose tissue pyruvate dehydrogenase in extracts of mitochondria is almost totally inactivated by incubation with ATP and can then be reactivated by incubation with 10mm-Mg(2+). In this respect its properties are similar to that of pyruvate dehydrogenase from heart and kidney where evidence has been given that inactivation and activation are catalysed by an ATP-dependent kinase and a Mg(2+)-dependent phosphatase. Evidence is given that insulin may act by increasing the proportion of active (dephosphorylated) pyruvate dehydrogenase. 6. Cyclic AMP could not be shown to influence the activity of pyruvate dehydrogenase in mitochondria under various conditions of incubation. 7. These results are discussed in relation to the control of fatty acid synthesis in adipose tissue and the role of cyclic AMP in mediating the effects of insulin on pyruvate dehydrogenase.
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PMID:Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. 515 98

Effects of norepinephrine on gluconeogenesis and ureogenesis from glutamine by hepatocytes from fasted rats were assessed. Comparisons were made to asparagine metabolism and to the effects of NH4Cl and dibutyryl cyclic AMP. With asparagine as substrate, aspartate content was very high but norepinephrine, dibutyryl cyclic AMP, or NH4Cl had little effect on gluconeogenesis or ureogenesis. Metabolism of asparagine could be greatly enhanced by the combination of oleate, ornithine, and NH4Cl. However, even under these conditions, asparatate content remained high, and norepinephrine and dibutyryl cyclic AMP had little influence on glucose or urea synthesis. With glutamine as substrate, aspartate content was much lower, but was greatly elevated by norepinephrine, dibutyryl cyclic AMP, or NH4Cl. Each of these effectors strongly stimulated glucose and urea formation from glutamine. NH4Cl stimulation was accompanied by an increased glutamate and decreased alpha-ketoglutarate content. This suggests the mechanism for NH4Cl stimulation is a near-equilibrium adjustment to ammonia by glutamate dehydrogenase and aspartate aminotransferase rather than a principal involvement of glutaminase. Although both norepinephrine and dibutyryl cyclic AMP lowered alpha-ketoglutarate to the same extent, norepinephrine more rapidly increased aspartate content and led to a smaller accumulation of glutamate than did dibutyryl cyclic AMP. Moreover, only norepinephrine led to a rapid increase in succinyl-CoA concentration. The catecholamine effect could not be explained by specific changes in cytosolic or mitochondrial redox states. The results suggest that alpha-ketoglutarate dehydrogenase is a site of catecholamine action in rat liver. Since purified alpha-ketoglutarate dehydrogenase is known to be Ca2+ stimulated and Ca2+ flux is involved in catecholamine action, these findings also suggest that mitochondrial Ca2+ is elevated by catecholamines.
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PMID:Glutamine metabolism of isolated rat hepatocytes. Evidence for catecholamine activation of alpha-ketoglutarate dehydrogenase. 609 58

1. The specific activity of NADP-dependent L-glutamate dehydrogenase (GDH) from T. cruzi epimastigotes increased from 0.7 at early log-phase to 1.4 mumol/min/mg of protein at the stationary phase. 2. When T. cruzi cells were incubated in the presence of L-glutamate (0.08%), the GDH had a specific activity of 2.2, much higher than that of cells incubated in the presence of D-glucose (0.08%), which was 1.2 mumol/min/mg of protein. 3. The specific activity of NADP-dependent GDH from cells incubated in the presence of L-glutamate did not vary when the cells were treated with cycloheximide (100 ng/ml) or chloramphenicol (0.5 mg/ml). 4. The activity of the NAD-dependent GDH did not change in any of the situations described above. 5. AMP, ADP, ATP, citrate, isocitrate, oxaloacetate, fructose-1,6-diP, pyruvate, L-proline and L-arginine did not have any effect on the NADP-linked GDH activity. Product inhibition studies were done on the latter GDH activity.
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PMID:Regulatory studies of L-glutamate dehydrogenase from Trypanosoma cruzi epimastigotes. 613 80

The effect of 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase [GTP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32], was tested on NH3 formation via the purine nucleotide cycle and glutamate dehydrogenase (EC 1.4.1.2). NH3 excretion in rats increased 70-fold after 48 h of NH4Cl feeding, from 12.2 +/- 4.5 to 862 +/- 190 mumol/mg of creatinine. At 4 h after a single intraperitoneal injection of 3-mercaptopicolinate into NH4Cl-fed rats, NH3 excretion was inhibited by 93%. Kidneys of NH4Cl-fed plus 3-mercaptopicolinate-treated rats, compared with those of NH4Cl-fed rats, showed a 3.5-fold increase in the content of IMP, 5-fold increase in adenylosuccinate, 4-fold increase in aspartate, and a 30% increase in AMP. 3-Mercaptopicolinate completely inhibited NH3 and glucose formation from glutamate in tubules from acidotic rats and NH3 formation from aspartate in kidney perfusion experiments. When transamination in tubules was prevented by 2-amino-4-methoxy-trans-but-3-enoic acid, formation of glucose, but not of NH3, from glutamate was inhibited. 3-Mercaptopicolinate completely inhibited NH3 formation from aspartate in the presence of the aminotransferase inhibitor in kidney tubules. The data show that NH3 can be formed via glutamate dehydrogenase and the purine nucleotide cycle at significant and approximately equal rates. 3-Mercaptopicolinate has no direct effect on NH3 formation via glutamate dehydrogenase, but inhibits that via the purine nucleotide cycle. We conclude that gluconeogenesis is not regulatory for NH3 formation in kidney.
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PMID:The relationship between glutamate deamination and gluconeogenesis in kidney. 613 15

Fourteen stable mutants of Mucor bacilliformis which grew yeastlike under both aerobic and anaerobic conditions were isolated after treatment of growing mycelium with N-methyl-N'-nitro-N-nitrosoguanidine. Biochemical characterization of the mutants included determination of growth in different carbon and nitrogen sources, determination of sensitivity of respiration to cyanide and salicylhydroxamate, analysis of cytochrome spectra, determination of glutamate dehydrogenases, glutamine synthase, and ornithine decarboxylase activities, and measurement of cyclic AMP levels. Data showed that all mutants were defective in some aspect of oxidative metabolism and had low levels of ornithine decarboxylase, whereas other characters were variable. It was concluded that morphological transition in M. bacilliformis is probably associated with mitochondrial functions and expression of ornithine decarboxylase, but may be independent of cyclic AMP and glutamate dehydrogenase levels. The importance of genetic studies in the analysis of dimorphism is stressed.
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PMID:Isolation and biochemical analysis of Mucor bacilliformis monomorphic mutants. 613 77

A method for measuring free fatty acids by enzymic cycling is described. Free fatty acids are converted to acyl-CoAs by acyl-CoA synthetase, then the acyl-CoAs are hydrolyzed back to the free fatty acids by acyl-CoA hydrolase in a cyclic fashion. The amounts of AMP produced during this cyclic reaction are determined from the absorbance at 340 nm in the presence of AMP deaminase and glutamate dehydrogenase. This method is sensitive to as low as 0.1 nmol of free fatty acids, and the standard curve is linear up to 1.0 nmol. This method shows a broad specificity for long-chain fatty acids (C12--C20) and the recoveries of fatty acids added to bacterial cell-free extracts are more than 90%.
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PMID:An enzymic cycling method for the determination of free fatty acids with acyl-CoA synthetase and acyl-CoA hydrolase. 613 47

Glutamic dehydrogenase extracted with tris buffer from fresh freeze-thawed rat heart mitochondria was purified by ammonium sulphate fractionation, affinity chromatography on GTP agarose, hydroxyapatite chromatography and concentration using a molecular sieve. The final specific activity is 80 units/mg protein. Thin gel SDS electrophoresis of the purified enzyme preparation after reduction with dithiothreitol shows a major band with a molecular weight of 38 000 Daltons. Two minor bands are also present. Sucrose density gradient centrifugation reveals a molecular weight of 230 000 Daltons for unreduced mitochondrial GDH activity. By gel filtration rat heart mitochondrial glutamic dehydrogenase has a major peak at 230 000 Daltons, a minor peak at 300 000 Daltons and some larger molecular weight species. Rat liver mitochondrial glutamic dehydrogenase has a minor peak at 230 000, a major peak at 300 000 and some larger molecular weight species. The rat liver mitochondrial glutamic dehydrogenase predominance at 300 000 is unchanged by incubation, extraction and purification with rat heart mitochondria. The purified GDH is stable frozen at -10 degrees C in tris-HCl buffer with EDTA. It loses activity at 4 degrees C especially when stored in 0.2 M phosphate buffer. It also loses activity when dialyzed for 24 h. This loss of activity is not completely prevented by adding nucleotides to the buffer (AMP or ADP) but is decreased by their presence.
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PMID:Glutamic dehydrogenase from rat heart mitochondria. I. Purification and physical properties including molecular weight determination. 672 19

The reaction catalyzed by bovine L-glutamate dehydrogenase is subjected to allosteric activation by ADP. We have measured the thermodynamic parameters (delta G0, delta H0, delta S0, and delta Cp) of the formation of the various possible binary and ternary complexes formed between the enzyme, NADPH, and either ADP or its analogs, adenosine, AMP, and ATP. delta H0 and delta Cp have been measured by flow calorimetry; delta G0 values obtained by calorimetry itself, differences spectroscopy, or gel filtration have been selected on the basis of accuracy under the conditions required for the formation of each complex. The data are interpreted in terms of "interaction parameters," the differences between the thermodynamic parameters of the formation of a ternary complex and the sum of those of the two related binary complexes. Both adnosine and ATP appear to loosen the binding of NADPH by simply preventing a subsite interaction of NADPH. AMP appears to have only minor and probably secondary effects. The negative effect of the binding of ADP on that of NADPH, however, involves the formation of a new interaction, which is exothermic, entropy compensated, has a moderately large negative delta Cp, and does not occur in either binary complex.
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PMID:The thermodynamics of a negatively interacting allosteric effector system. The glutamate dehydrogenase . NADPH . ADP complexes. 718 37


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