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)

Acetyl-CoA synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100%. Most of the activity of the three enzymes was recovered in the crude mitochondrial fraction. On subfractionation of this crude mitochondrial fraction with continuous sucrose density gradients, most of the activity of the three enzymes was found at a higher density than NAD+-isocitrate dehydrogenase and at about the same density as glutamate dehydrogenase, confirming earlier reported data for acetyl-CoA synthase. The finding that propionyl-CoA synthase and butyryl-CoA synthase had about the same distribution in the gradients as acetyl-CoA synthase adds support to the hypothesis that mitochondria involved in the metabolism of these short-chain fatty acids (all three of which have been shown to result in a rapid and high labelling of glutamine in vivo) form a distinct subpopulation of the total mitochondrial population. The three synthase activities were found to differ from each other in their rate of change and their subcellular localization during rat brain development. This, in combination with the observation that in gradients of adult brain preparations the three activities did not completely overlap, suggests that the three synthase activities are not present in the same proportion to each other in the same subpopulation (s) of mitochondria in the brain.
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PMID:Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development. 0 95

Glutamate synthase from Escherichia coli K-12 exhibits NH3-dependent activity. NH3-dependent activity is increased approximately 5-fold in apoglutamate synthase lacking flavin and non-heme iron. Whereas glutamine plus 2-oxoglutarate have the capacity to reoxidize the chemically reduced flavoenzyme, no such reoxidation is obtained with 2-oxoglutarate plus NH3. These results establish that the glutamine- and NH3-dependent syntheses of glutamate occur by different pathways of electron transfer from NADPH. The NH3-dependent activity of native and apoglutamate synthase exhibits similar catalytic properties. Some properties of apoglutamate synthase are similar to those of glutamate dehydrogenase. These properties include pH optima for synthesis and oxidative deamination of glutamate, inactivation by alkylating reagents and p-mercuribenzoate, an enhanced rate of inactivation by alkylating reagents and p-mercuribenzoate at low pH, 2-oxoglutarate protection against inactivation by p-mercuribenzoate, and reactivation of p-mercuribenzoate-treated enzyme by 2-mercaptoethanol. 2-Oxoglutarate protects against alkylation of glutamate synthase by iodo [1-14C]acetamide and reduces incorporation of methyl [1-14C]carboxamide into the small subunit of the enzyme.
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PMID:Properties of apoglutamate synthase and comparison with glutamate dehydrogenase. 0 50

Nitrogenase biosynthesis in Klebsiella pneumoniae including mutant strains, which produce nitrogenase in the presence of NH+4 (Shanmugam, K.T., Chan, Irene, and Morandi, C. (1975) Biochim. Biophys. Acta 408, 101--111) is repressed by a mixture of L-amino acids. Biochemical analysis shows that glutamine synthetase activity in strains SK-24, SK-28, and SK-29 is also repressed by amino acids, with no detectable effect on glutamate dehydrogenase. Among the various amino acids, L-glutamine in combination with L-aspartate was found to repress nitrogenase biosynthesis completely. In the presence of high concentrations of glutamine (1 mg/ml) even NH+4 repressed nitrogenase biosynthesis in the strains SK-27, SK-37, SK-55 and SK-56. Under these conditions, increased glutamate dehydrogenase activity was also detected. Physiological studies show that nitrogenase derepressed strains are unable to utilize NH+4 as sole source of nitrogen for biosynthesis of glutamate for biosynthesis of glutamate, whereas back mutations leading to NH+4 utilization results in sensitivity to repression by NH+4. These findings suggest that amino acids play an important role as regulators of nitrogen fixation.
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PMID:Amino acids as repressors of nitrogenase biosynthesis in Klebsiella pneumoniae. 0 1

The primary steps of N2, ammonia and nitrate metabolism in Klebsiella pneumoniae grown in a continuous culture are regulated by the kind and supply of the nitrogenous compound. Cultures growing on N2 as the only nitrogen source have high activities of nitrogenase, unadenylated glutamine synthetase and glutamate synthase and low levels of glutamate dehydrogenase. If small amounts of ammonium salts are added continuously, initially only part of it is absorbed by the organisms. After 2-3 h complete absorption of ammonia against an ammonium gradient coinciding with an increased growth rate of the bacteria is observed. The change in the extracellular ammonium level is paralleled by the intracellular glutamine concentration which in turn regulates the glutamine synthesis and an induction of glutamate dehydrogenase synthesis. Upon deadenylation these events are reversed.--Addition of dinitrophenol causes transient leakage of intracellular ammonium into the medium.
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PMID:Ammonium uptake and metabolism by mitrogen fixing bacteria. II. Klebsiella pneumoniae. 1 59

Glutamate synthase was purified about 250-fold from Thiobacillus thioparus and was characterized. The molecular weight was estimated as 280,000 g/mol. The enzyme showed absorption maxima at 280, 380, and 450 nm and was inhibited by Atebrin, suggesting that T. thioparus glutamate synthase is a flavoprotein. The enzyme activity was also inhibited by iron chelators and thiolbinding agents. The enzyme was specific for reduced nicotinamide adenine dinucleotide phosphate (NADPH) and alpha-ketoglutarate, but L-glutamine was partially replaced by ammonia as the amino donor. The Km values of glutamate synthase for NADPH, alpha-ketoglutarate, and glutamine were 3.0 muM, 50 muM, and 1.1 mM, respectively. The enzyme had a pH optimum between 7.3 and 7.8. Glutamate synthase from T. thioparus was relatively insensitive to feedback inhibition by single amino acids but was sensitive to the combined effects of several amino acids. Enzymes involved in glutamate synthesis in T. thioparus were studied. Glutamine synthetase and glutamate synthase, as well as two glutamate dehydrogenases (NADH and NADPH dependent), were present in this organism. This levels of glutamate synthase and glutamate dehydrogenase were similar in T. thioparus grown on 0.7 or 7.0 mM ammonium sulfate. The sum of the activities of both glutamate dehydrogenases was only 1/25 of that of glutamate synthase under the assay conditions. It was concluded that the glutamine pathway is important for ammonia assimilation in this autotrophic bacterium.
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PMID:Purification and properties of glutamate synthase from Thiobacillus thioparus. 1 19

Glutamine synthetase (EC 6.3.1.2) was localized within the matrix compartment of avian liver mitochondria. The submitochondrial localization of this enzyme was determined by the digitonin-Lubrol method of Schnaitman and Greenawalt (35). The matrix fraction contained over 74% of the glutamine synthetase activity and the major proportion of the matirx marker enzymes, malate dehydrogenase (71%), NADP-dependent isocitrate dehydrogenase (83%), and glutamate dehydrogenase (57%). The highest specific activities of these enzymes were also found in the matrix compartment. Oxidation of glutamine by avian liver mitochondria was substantially less than that of glutamate. Bromofuroate, an inhibitor of glutamate dehydrogenase, blocked oxidation of glutamate and of glutamine whereas aminoxyacetate, a transaminase inhibitor, had little or no effect with either substrate. These results indicate that glutamine metabolism is probably initiated by the conversion of glutamine to glutamate rather than to an alpha-keto acid. The localization of a glutaminase activity within avian liver mitochondria plus the absence of an active mitochondrial glutamine transaminase is consistent with the differential effects of the transaminase and glutamate dehydrogenase inhibitors. The high glutamine synthetase activity (40:1) suggests that mitochondrial catabolism of glutamine is minimal, freeing most of the glutamine synthesized for purine (uric acid) biosynthesis.
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PMID:Submitochondrial localization and function of enzymes of glutamine metabolism in avian liver. 1 18

The product of a newly identified gene, glnF, which is distinct from the glutamine synthetase structural gene (glnA), is required for synthesis of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2[ in Salmonella typhimurium and probably in Escherichia coli. Salmonella strains with ICR (2-chloro-6-methoxy-9-[3-(2-chloroethyl)aminopropylamino]acridine dihyodrochloride)-induced (frameshift) mutations in glnF are glutamine auxotrophs; they have less than 10% oof wild-type glutamine synthetase activity or antigen and are unable to derepress the synthesis of the enzyme. The mutant allele is recessive to the wild-type allele, indicating that the glnF gene encodes a diffusible product. Mutant glnF strains have normal activities of all proteins involved in covalent modification of glutamine synthetase: adenylyltransferase (EC 2.7.7.42), PII, uridylyltransferase, and uridylyl removing enzyme. In addition, they have glutamate synthase (EC 1.4.1.13) and glutamate dehydrogenase (EC 1.4.1.4) activities. Thus, glnF does not encode the structure of any of these proteins. The above evidence suggests that the product of the glnF gene is (or produces) a positive regulatory factor that is required for synthesis of glutamine synthetase; it indicates that auto-regulation cannot account for control of the synthesis of glutamine synthetase in Salmonella.
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PMID:The product of a newly identified gene, gInF, is required for synthesis of glutamine synthetase in Salmonella. 1 62

Administering D-aldosterone, 7 microgram 100 g-1, to rats results in a marked rise in ammonium excretion and metabolic alkalosis. Increased ammonium excretion is not related to either a significant elevation in potassium excretion nor to hypokalemia. Consequently, potassium depletion does not appear to be the causative factor in the aldosterone-stimulated ammonium excretion. Isolated kidneys from aldosterone-treated rats, perfused with 1 mM L-glutamine, produced twice as much ammonia from glutamine as did controls. Ammonia production per glutamine extracted increased from 1.33 +/- 0.07 in control to 1.79 +/- 0.08 in kidneys from hormone-treated rats, suggesting stimulation of the mitochondrial glutaminase I-glutamate dehydrogenase pathway; this was supported by a proportional rise in production of glucose and CO2, end products of glutamine's carbon skeleton. Consequently, aldosterone-stimulated renal ammonia production, by specifically activating the mitochondrial pathway, leads to the elimination of hydrogen ions in the form of urinary ammonium excretion and an ensuing metabolic alkalosis.
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PMID:Influence of aldosterone on renal ammonia production. 1 22

A mutant (gltB) of Escherichia coli lacking glutamate synthase (GOGAT) was unable to utilize a wide variety of compounds as sole nitrogen source (e.g., arginine, proline, gamma-aminobutyrate, and glycine). Among revertants of these Asm- strains selected on one of these compounds (e.g., arginine, proline, or gamma-aminobutyrate) were those that produce glutamine synthetase (GS) constitutively (GlnC phenotype). These revertants had a pleiotropically restored ability to grow on compounds that are metabolized to glutamate. This suggested that the expression of the genes responsible for the metabolism of these nitrogen sources was regulated by GS. An examination of the regulation of proline oxidase confirmed this hypothesis. The differential sensitivities of GlnC and wild-type strains to low concentrations (0.1 mM) of the glutamine analog L-methionine-DL-sulfoximine supported the conclusion that the synthesis of a glutamine permease was also positively controlled by GS. During the course of this study we found that the reported position of the locus (gltB) for glutamate synthase is incorrect. We have relocated this gene to be 44% linked to the argG locus by P1 transduction. Further mapping has shown that the locus previously called aspB is in reality the gltB locus and that the "suppressor" of the aspB mutation (A. M. Reiner, J. Bacteriol. 97:1431-1436, 1969) is the locus for glutamate dehydrogenase (gdhA).
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PMID:gltB gene and regulation of nitrogen metabolism by glutamine synthetase in Escherichia coli. 2 35

Substrate oxidation by rat kidney slices regulates renal ammoniagenesis from glutamine. At concentrations close to those expected in plasma, lactate alone, or combined with other renal fuels, inhibits ammoniagenesis markedly; glucose and citrate decrease ammoniagenesis slightly. However, lactate, citrate, and glucose inhibit ammoniagenesis of kidney slices from acidotic rats less than ammoniagenesis of kidney slices from control rats. Lesser inhibition of ammoniagenesis is seen also when acidotic slices rather than control slices are incubated in the presence of all the tested substrates combined in the same medium. In addition to decreasing the ammoniagenesis of renal slices from control rats, the presence of lactate causes an augmented accumulation of glutamate. In contrast, adding lactate to acidotic slices does not increase glutamate accumulation nearly as much. When glutamate is substituted for glutamine in the medium, lactate still decreases ammonia production, but to a lesser extent with acidotic slices. Changes in medium pH from 7.0 to 7.8 have no, or only small, overall effects on net renal slice ammonia production from glutamine under any of the circumstances tested. We conclude that lactate alone and combined with other substrates decreases ammoniagenesis primarily at the glutamate dehydrogenase step and that slices from acidotic rats are relatively resistant to substrate mediated inhibition.
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PMID:The regulations of renal ammoniagenesis in the rat by extracellular factors. I. The combined effects of acidosis and physiologic fuels. 3 19


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