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)

Evidence for the existence of a glutamine cycle in Neurospora crassa is reviewed. Through this cycle glutamine is converted into glutamate by glutamate synthase and catabolized by the glutamine transaminase-omega-amidase pathway, the products of which (2-oxoglutarate and ammonium) are the substrates for glutamate dehydrogenase-NADPH, which synthesizes glutamate. In the final step ammonium is assimilated into glutamine by the action of a glutamine synthetase (GS), which is formed by two distinct polypeptides, one catalytically very active (GS beta), and the other (GS alpha) less active but endowed with the capacity to modulate the activity of GS alpha. Glutamate synthase uses the amide nitrogen of glutamine to synthesize glutamate; glutamate dehydrogenase uses ammonium, and both are required to maintain the level of glutamate. The energy expended in the synthesis of glutamine drives the cycle. The glutamine cycle is not futile, because it is necessary to drive an effective carbon flow to support growth; in addition, it facilitates the allocation of nitrogen or carbon according to cellular demands. The glutamine cycle which dissipates energy links catabolism and anabolism and, in doing so, buffers variations in the nutrient supply and drives energy generation and carbon flow for optimal cell function.
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PMID:Glutamine metabolism and cycling in Neurospora crassa. 214 4

The nac (nitrogen assimilation control) gene from Klebsiella aerogenes, cloned in a low-copy-number cloning vector, restored the ability of K. aerogenes nac mutants to activate histidase and repress glutamate dehydrogenase formation in response to nitrogen limitation and to limit the maximum expression of the nac promoter. When present in Salmonella typhimurium, the K. aerogenes nac gene allowed the hut genes to be activated during nitrogen-limited growth. Thus, the nac gene encodes a cytoplasmic factor required for activation of hut expression in S. typhimurium during nitrogen-limited growth.
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PMID:Cloning of the Klebsiella aerogenes nac gene, which encodes a factor required for nitrogen regulation of the histidine utilization (hut) operons in Salmonella typhimurium. 225 73

1. Glutamine was found to be the main carbon and nitrogen product of the metabolism of aspartate in isolated guinea-pig kidney-cortex tubules. Glutamate, ammonia and alanine were only minor products. 2. Carbon-balance calculations and the release of 14CO2 from [U-14C]aspartate indicate that oxidation of the aspartate carbon skeleton occurred. 3. A pathway involving aspartate aminotransferase, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate dehydrogenase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of aspartate into glutamine. 4. Evidence for this pathway was obtained by: (i) inhibiting aspartate removal by amino-oxyacetate, an inhibitor of transaminases, (ii) the use of methionine sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from aspartate, (iii) the use of quinolinate, an inhibitor of phosphoenolpyruvate carboxykinase, which inhibited glutamine synthesis from aspartate, (iv) the use of alpha-cyano-4-hydroxycinnamate, an inhibitor of the mitochondrial transport of pyruvate, which caused an accumulation of pyruvate from aspartate, and (v) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from aspartate.
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PMID:Glutamine synthesis from aspartate in guinea-pig renal cortex. 236 82

To contribute to our understanding of nitrogen metabolism in the developing chick we have studied in liver, intestine and yolk sac membrane the ontogeny of both aspartate- and alanine transaminases, glutamate dehydrogenase, adenylate deaminase, glutamine synthetase and xanthine dehydrogenase activities. Liver enzyme activities were much higher than those of the same enzymes in intestine and yolk sac membrane, the latter having the lowest activities. In the liver, both alanine transaminase and glutamate dehydrogenase increased their activity just before hatching, xanthine dehydrogenase and glutamine synthetase develop their highest activity just after hatching, while aspartate transaminase and adenylate deaminase attained the highest levels just with adulthood. From the pattern of enzyme activity in yolk sac membrane and intestine it can be inferred that after hatching, the amino-acid metabolism in these tissues is considerably enhanced, with higher production of ammonia from amino acids, as indicated by the rise in adenylate deaminase, as well as increased potentiality in production of both alanine and glutamine. It can be concluded that hatching coincides with a deep change of pace in amino-acid metabolism in the organs studied fully comparable with that observed in Mammals at the end of lactation, with the difference that the adaptation to the new diet in the case of the chick is much more sudden than weaning is for the rat.
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PMID:Amino-acid metabolism enzyme activities in the liver, intestine and yolk sac membrane of developing domestic fowl. 243 52

L-[amide-13N]glutamine in Neurospora crassa is metabolized to [13N]glutamate by glutamate synthase and to [13N]ammonium by the glutamine transaminase-omega-amidase pathway. The [13N]ammonium released is assimilated by glutamate dehydrogenase and glutamine synthetase, confirming the operation of a glutamine cycle. Most of the nitrogen is retained during cycling between glutamate and glutamine.
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PMID:13N isotope studies of glutamine assimilation pathways in Neurospora crassa. 252 94

The nucleotide sequence of the Aspergillus nidulans gdhA gene encoding NADP linked glutamate dehydrogenase has been determined and Northern blot analysis used to study the regulation of expression of this gene. The gdhA gene is 1485 nucleotides long and, by comparison with the corresponding Neurospora crassa am gene, has two putative introns of 53 nucleotides and a protein encoding region of 1380 nucleotides that codes for an inferred protein of 49.63 kDa which shows regions of homology with glutamate dehydrogenase proteins from a range of organisms. mRNA analysis of wild-type mycelium grown under a variety of conditions shows that: (a) the highest levels are seen with glucose as the carbon source with inorganic nitrogen; and (b) no gdhA mRNA is detectable when cells are transferred to amino acids as sole carbon source, closely matching the observed glutamate dehydrogenase activity levels under identical conditions. The results presented strongly suggest that a good carbon source is a prerequisite for transcription, but the molecular mechanism responsible is unclear.
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PMID:Nucleotide sequence and regulation of expression of the Aspergillus nidulans gdhA gene encoding NADP dependent glutamate dehydrogenase. 255 Jul 58

Streptomyces fradiae has two chromatographically distinct forms of glutamate dehydrogenase (GDH): one GDH utilizes NAD as coenzyme, the other uses NADP. The intracellular level of both GDHs is strongly regulated by the nitrogen source in the growth medium. NADP-dependent GDH was purified to homogeneity from crude extracts of S. fradiae. The Mr of the native enzyme was determined to be 200,000 by size-exclusion high-performance liquid chromatography whereas after sodium dodecyl sulphate-polyacrylamide gel electrophoresis one major band of Mr 49,000 was found, suggesting that the enzyme is a tetramer. The enzyme was highly specific for the substrates 2-oxoglutarate and L-glutamate, and required NADP, which could not be replaced by NAD, as a cofactor. The pH optimum was 9.2 for oxidative deamination of glutamate and 8.4 for reductive amination of 2-oxoglutarate. The Michaelis constants (Km) were 28.6 mM for L-glutamate and 0.12 mM for NADP. Km values for reductive amination were 1.54 mM for 2-oxoglutarate, 0.07 mM for NADPH and 30.8 mM for NH+4. The enzyme activity was significantly reduced by adenine nucleotides, particularly ATP.
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PMID:Purification and properties of NADP-dependent glutamate dehydrogenase from Streptomyces fradiae. 256 88

Pathways of ammonia assimilation into glutamic acid were investigated in ammonia-grown and N2-fixing Clostridium kluyverii and Clostridium butyricum by measuring the specific activities of glutamate dehydrogenase, glutamine synthetase, and glutamate synthase. C. kluyverii had NADPH-glutamate dehydrogenase with a Km of 12.0 mM for NH4+. The glutamate dehydrogenase pathway played an important role in ammonia assimilation in ammonia-grown cells but was found to play a minor role relative to that of the glutamine synthetase/NADPH-glutamate synthase pathway in nitrogen-fixing cells when the intracellular NH4+ concentration and the low affinity of the enzyme for NH4+ were taken into account. In C. butyricum grown on glucose-salt medium with ammonia or N2 as the nitrogen source, glutamate dehydrogenase activity was undetectable, and the glutamine synthetase/NADH-glutamate synthase pathway was the predominant pathway of ammonia assimilation. Under these growth conditions, C. butyricum also lacked the activity of glucose-6-phosphate dehydrogenase, which catalyzes the regeneration of NADPH from NADP+. However, high activities of glucose-6-phosphate dehydrogenase as well as of NADPH-glutamate dehydrogenase with a Km of 2.8 mM for NH4+ were present in C. butyricum after growth on complex nitrogen and carbon sources. The ammonia-assimilating pathway of N2-fixing C. butyricum, which differs from that of the previously studied Bacillus polymyxa and Bacillus macerans, is discussed in relation to possible effects of the availability of ATP and of NADPH on ammonia-assimilating pathways.
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PMID:Ammonia assimilation pathways in nitrogen-fixing Clostridium kluyverii and Clostridium butyricum. 256 48

LLC-PK1 kidney epithelial cells grown under the condition of continuous rocking exhibit a variety of differentiated functions of proximal tubular epithelium, including pH-modulated ammoniagenesis. To further determine their value as a model system, we investigated the pathways of ammoniagenesis under both normal conditions and acid-base manipulations. Pulse-chase studies with carbon 14-labeled glutamine demonstrated a marked delay in glutamine conversion to glutamate, indicating that glutamine deamidation is a critical rate-limiting step, and also provided evidence for metabolism of the glutamine carbon skeleton by the tricarboxylic acid cycle. Ammonia and alanine were the predominant nitrogen metabolites of glutamine at all pH conditions, and the stoichiometry suggested that glutamate is metabolized through both glutamate dehydrogenase and glutamate transaminase at pH 7.4. Increased ammonia production in response to a low pH was associated with increased flux through phosphate-dependent glutaminase and the glutamate transamination pathway and was accompanied by a fall in intracellular glutamate and alpha-ketoglutarate concentrations, which was similar to events in the intact kidney. Studies with the inhibitors acivicin and amino oxyacetate suggested that the gamma-glutamyltranspeptidase and glutamine transamination pathways are inconsequential in LLC-PK1 cells. The phosphate-dependent glutaminase pathway appears to play a predominant role in the regulation of ammoniagenesis. The similarity in ammonia metabolism with other in vitro and in vivo models suggests that LLC-PK1 cells will be a useful system for investigating renal ammoniagenesis and the intracellular signals that modulate this process.
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PMID:Pathways and regulation of ammoniagenesis by the LLC-PK1 cells in culture. 257 Jan 15

Neurospora crassa wild-type is almost unable to grow on glutamine as sole nitrogen and carbon source but a GDH-; GS +/- double mutant strain, lacking NADP-dependent glutamate dehydrogenase and partially lacking glutamine synthetase did grow. Under these conditions, the double mutant had a higher chemical energy content than the wild-type. Enzyme assays and labelling experiments with glutamine indicated that in the double mutant glutamine was degraded to ammonium and to carbon skeletons by glutamate synthase, the catabolic (NADH-dependent) glutamate dehydrogenase and the glutamine transaminase-omega-amidase pathway.
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PMID:Glutamine assimilation pathways in Neurospora crassa growing on glutamine as sole nitrogen and carbon source. 257 59


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