Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principal initial product of metabolism of [13N]N2 and 13NH4+ by five diverse cyanobacteria is glutamine. Methionine sulfoximine inhibits formation of [13N]glutamine except in the case of Gloeothece sp., an organism with a thick sheath through which the inhibitor may not penetrate. Thus, glutamine synthetase appears to catalyze the initial step in the assimilation of N2-derived or exogenous NH4+ by these organisms. [13N]Glutamate is, in all cases, the second major product of assimilation of 13N-labeled N2 and NH4+. In all of the N2-fixing cyanobacteria studied, the fraction of 13N in glutamine declines and that in glutamate increases with increasing times of assimilation of [13N]N2 and 13NH4+, and (Gloeothece again excepted) methionine sulfoximine reduces incorporation of 13N into glutamate as well as into glutamine. Glutamate synthase therefore appears to catalyze the formation of glutamate in a wide range of N2-fixing cyanobacteria. However, the major fraction of [13N]glutamate formed by Anacystis nidulans incubated with 13NH4+ may be formed by glutamic acid dehydrogenase. The formation of [13N]alanine from 13NH4+ appears to be catalyzed principally either by alanine dehydrogenase (as in Cylindrospermum licheniforme) or by a transaminase (as in Anabaena variabilis).
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PMID:Pathways of assimilation of [13N]N2 and 13NH4+ by cyanobacteria with and without heterocysts. 41 57

The glutamate dehydrogenase from a single human liver has been studied. The subunit size was found to be 55,200 +/- 1,500 by sedimentation equilibrium. The partial specific volume is 0.732 as calculated from the amino acid composition. The sequence was determined by isolation of peptides after cyanogen bromide (CNBr) cleavage; the fraction containing the largest peptides was hydrolyzed by trypsin after maleylation. Studies on these peptides accounted for 454 residues of the 505 residues that are presumably present in the protein. For the 51 residues that were not represented in isolated peptides, we have tentatively assumed that the sequence is the same as that of the bovine enzyme. Methionine and arginine residues in these peptides could be placed on the basis of the specificity of cleavage by CNBr or trypsin. In all, 349 residues were placed in sequence, and were aligned by homology with the corresponding peptides of the bovine and chicken enzymes. From the present information, there are 24 known differences in sequence between the human and bovine enzymes and 41 between the human and chicken enzymes. In addition, the human enzyme contains 4 additional residues at the NH2 terminus as compared to the bovine enzyme. In a peptide from the human enzyme, an additional residue, isoleucine 385, was detected by automated Edman degradation. Reinvestigation of the bovine sequence demonstrated that this residue is also present in the bovine enzyme (and presumably in the chicken enzyme also). Residue 384 of the bovine enzyme, previously reported as Glx has now been shown to be glutamine.
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PMID:Partial amino acid sequence of the glutamate dehydrogenase of human liver and a revision of the sequence of the bovine enzyme. 42 60

The purpose of this study was to investigate factors which may regulate ammoniagenesis in the kidney cortex. Emphasis was placed on the segment of the pathway by which the carbons derived from glutamine must exit from the mitochondrion. These pathways were compared in the rat with high rates of ammoniagenesis and the rabbit which has a low rate of ammoniagenesis. The dicarboxylate transporter, which is essential for ammoniagenesis, has a maximum velocity which was much lower in the rabbit. The malate concentration required for half-maximal rates of transport was 14 nmol/mg mitochondrial protein and similar in both species. There was no effect of chronic metabolic acidosis on dicarboxylate transporter activity. The tricarboxylate transporter activity with phosphoenol pyruvate as substrate also had a low activity in the rabbit kidney-cortex mitochondria. The maximum velocity of phosphate dependent glutaminase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase were all much greater than the maximal rate of ammoniagenesis observed in vivo in the rabbit. Therefore, the low rates of ammoniagenesis and the failure to adapt to acidosis in the rabbit are best explained by factors influencing the dicarboxylate transporter.
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PMID:Role of the mitochondrial anion transporters in the regulation of ammoniagenesis in renal cortex mitochondria of the rabbit and rat. 49 11

1. The concentration of HCO3- (independent of any change of pH) exerts different effects on glutamine metabolism in rat kidney-cortex tubules, hepatocytes and enterocytes.2. In kidney tubules HCO3- (10.5-50 MM) has no effect on glutaminase (EC 3.5.1.2), whereas glutamate dehydrogenase (EC 1.4.1.3) is inhibited as HCO3- concentration is increased. The result is that flux through the entire glutamate-to-glucose pathway is inhibited by increasing HCO3- concentrations. A large proportion (more than 30%) of the glutamine removed undergoes complete oxidation. 3. In hepatocytes, and to a smaller extent in enterocytes, HCO3- is an accelerator of glutaminase. Synthesis of glucose and urea from glutamine in hepatocytes increases as HCO3- concentration is increased. Calculations show that fumarate, formed via aspartate aminotransferase and arginino-succinate lyase, is the precursor of the glucose. There is no complete oxidation of the carbon skeleton of glutamine in hepatocytes. 4. Leucine at near-physiological concentrations (0.1-1 mM) is an accelerator of glutaminase in hepatocytes, but not in kidney tubules or in enterocytes. 5. The results are discussed in relation to regulation of acid/base balance in vivo.
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PMID:A role for bicarbonate in the regulation of mammalian glutamine metabolism. 54 52

In cerebral blood flow deficiency the level of ammonia in the cerebral tissue is appreciably increased and the activity of glutamate dehydrogenase (GDH) is decreased without material variations in the content of glutamine and amide groups of protein. Favouring normalization of the deranged cerebral blood flow, euphylline neutralizes excess ammonia by means of GDH activity recovery in the reduction amination reaction. The drug exhibited the most pronounced effect during acute cerebral ischemia. This indicates that euphylline influences the neurochemical mechanisms of the compensatory regulation of cerebral blood flow.
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PMID:[Neurochemical mechanisms of the effect of euphylline in cerebral blood flow deficiency]. 54 Jan 49

Using renal cortical slices from acidotic and normal dogs we show that fatty acids such as crotonate, octanoate, palmitate and oleate as well as ketone bodies (beta-hydroxybutyrate and acetoacetate) in concentrations ranging from 0.5 to 5.0 mM induce a 30 to 50% decrease in glutamine uptake and ammonia production when glutamine (1 mM) is used as the basic substrate. Glucose production also decreases by 20 to 30%. Glutamate release in the incubation medium is significantly augmented by fatty acids or ketones. When glutamate 5 mM is used as substrate instead of glutamine, glutamate uptake, ammoniagenesis and glucose production are significantly depressed by fatty acids and ketones. Increased glutamate release from glutamine, decreased glutamate uptake and decreased gluconeogenesis from glutamine or glutamate provide evidence that ketone bodies and fatty acids depress the net flux through the glutamate dehydrogenase reaction invovled in glutamine metabolism. This is further supported by the fact that addition of ketones to alpha-ketoglutarate and ammonia stimulates net glutamate synthesis by kidney tubules.
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PMID:Relationship between the renal metabolism of glutamine, fatty acids and ketone bodies. 61 72

The metabolism of proline was studied in liver cells isolated from starved rats. The following observations were made. 1. Consumption of proline could be largely accounted for by production of glucose, urea, glutamate and glutamine. 2. At least 50% of the total consumption of oxygen was used for proline catabolism. 3. Ureogenesis and gluconeogenesis from proline could be stimulated by partial uncoupling of oxidative phosphorylation. 4. Addition of ethanol had little effect on either proline uptake or oxygen consumption, but strongly inhibited the production of both urea and glucose and caused further accumulation of glutamate and lactate. Accumulation of glutamine was not affected by ethanol. 5. The effects of ethanol could be overcome by partial uncoupling of oxidative phosphorylation. 6. The apparent K(m) values of argininosuccinate synthetase (EC 6.3.4.5) for aspartate and citrulline in the intact hepatocyte are higher than those reported for the isolated enzyme. 7. 3-Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (EC 4.1.1.32), greatly enhanced cytosolic aspartate accumulation during proline metabolism, but inhibited urea synthesis. 8. It is concluded that when proline is provided as a source of nitrogen to liver cells, production of ammonia by oxidative deamination of glutamate is inhibited by the highly reduced state of the nicotinamide nucleotides within the mitochondria. 9. Conversion of proline into glucose and urea is a net-energy-yielding process, and the high state of reduction of the nicotinamide nucleotides is presumably maintained by a high phosphorylation potential. Thus when proline is present as sole substrate, the further oxidation of glutamate by glutamate dehydrogenase (EC 1.4.1.3) is limited by the rate of energy expenditure of the cell.
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PMID:Prolone metabolism in isolated rat liver cells. 64 9

Growing cells of Yersinia pseudotuberculosis, but not those of closely related Yersinia pestis, rapidly destroyed exogenous L-aspartic and L-glutamic acids, thus prompting a comparative study of dicarboxylic amino acid catabolism. Rates of amino acid metabolism by resting cells of both species were determined at pH 5.5, 7.0, and 8.5. Regardless of pH, Y. pseudotuberculosis destroyed L-glutamic acid, L-glutamine, L-aspartic acid, and L-asparagine at rates greater than those observed for Y. pestis. Although rates of proline degardation were similar, its metabolism by Y. pestis at pH 8.5 resulted in excretion of glutamic and aspartic acids. Similarly, Y. pestis excreted aspartic acid when incubated with L-glutamic acid (pH 8.5) or L-asparagine (pH 5.5, 7.0, and 8.5). Aspartase activity was not detected in extracts of 10 strains of Y. pestis but was present in all 11 isolates of Y. pseudotuberculosis. The latter contained significantly more glutaminase, asparaginase, and L-glutamate-oxalacetate transminase activity than did extracts of Y. pestis; specific activities of L-glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase were similar. The observed differences in dicarboxylic amino acid metabolism are traceable to asparatase deficiency in Y. pestis and may account for the slow doubling time of this organism relative to Y. pseudotuberculosis.
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PMID:Consequences of aspartase deficiency in Yersinia pestis. 71 77

With either alanine or a mixture of 15 different amino acids as nitrogen source, the addition of L-leucine inhibited the synthesis of urea by isolated rat liver cells. With alanine present leucine promoted the production of glutamate and glutamine. Comparison of effects of leucine on soluble glutamate dehydrogenase, mitochondria and isolated cells supports the postulate that leucine exerts its effect through activation of glutamate dehydrogenase. It is suggested that this latter enzyme may not be as important for the production of NH3 for carbamoyl phosphate synthesis as has been considered hitherto.
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PMID:The effects L-leucine on the synthesis of urea, glutamate and glutamine by isolated rat liver cells. 80 18

1. The apparent Michaelis constants of the glutamate dehydrogenase (EC 1.4.1.3), the glutamate-oxaloacetate transaminase (EC 2.6.1.1) and the glutaminase (EC 3.5.1.2) of rat brain mitochondria derived from non-synaptic (M) and synaptic (SM2) sources were studied. 2. The kinetics of oxygen uptake of both populations of mitochondria in the presence of a fixed concentration of malate and various concentrations of glutamate or glutamine were investigated. 3. In both mitochondrial populations, glutamate-supported respiration in the presence of 2.5 mM-malate appears to be biphasic, one system (B) having an apparent Km for glutamate of 0.25 +/- 0.04 mM (n=7) and the other (A) of 1.64 +/- 0.5 mM (n=7) [when corrected for low-Km process, Km=2.4 +/- 0.75 mM (n=7)]. Aspartate production in these experiments followed kinetics of a single process with an apparent Km for glutamate of 1.8-2 mM, approximating to the high-Km process. 4. Oxygen-uptake measurement with both mitochondrial populations in the presence of malate and various glutamate concentrations in which amino-oxyacetate was present showed kinetics approximating only to the low-Km process (apparent Km for glutamate approximately 0.2 mM). Similar experiments in the presence of glutamate alone showed kinetics approximating only to the high-Km process (apparent Km for glutamate approximately 1-1.3 mM). 5. Oxygen uptake supported by glutamine (0-3 mM) and malate (2.5 mM) by the free (M) mitochondrial population, however, showed single-phase kinetics with an apparent Km for glutamine of 0.28 mM. 6. Aspartate and 2-oxoglutarate accumulation was measured in 'free' nonsynaptic (M) brain mitochondria oxidizing various concentrations of glutamate at a fixed malate concentration. Over a 30-fold increase in glutamate concentration, the flux through the glutamate-oxaloacetate transaminase increased 7--8-fold, whereas the flux through 2-oxoglutarate dehydrogenase increased about 2.5-fold. 7. The biphasic kinetics of glutamate-supported respiration by brain mitochondria in the presence of malate are interpreted as reflecting this change in the relative fluxes through transamination and 2-oxoglutarate metabolism.
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PMID:Comparative studies on glutamate metabolism in synpatic and non-synaptic rat brain mitochondria. 88 64


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