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:1.4.3.11 (glutamate dehydrogenase)
4,437 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reaction network of intermediary metabolism in the mammalian cell has been studied using linear optimization. Experimental measurements of metabolite fluxes entering and leaving hybridoma cell line 167.4G5.3 have been used to interpret the interactions of nutrients and the demand for intermediates for growth. We have ascertained the effects of waste production and energy loads on the cell growth rate using linear optimization. This analysis has shown that neither the maintenance demand for ATP nor the antibody production rate limit growth rate at normal experimental conditions. In addition, the cell uses its nutrients for growth with only 57-78% efficiency, due to the large secretion of alanine. The sensitivity of the growth rate with respect to the demand for cofactors and the supply of nutrients is given by the shadow price for each constraint. The shadow prices have shown that amino acids are the limiting nutrients at experimental conditions. The sensitivities of the growth rate to flux through reactions, given by the reduced costs, have shown that flux through the reaction glutamate dehydrogenase may actually slow down cell growth. We have also found that intermediates with lower shadow prices, and thus with lower value to the cell, are the precursors to compounds secreted from the cell. The shadow prices are also a means for comparing the costs of synthesizing various intermediates in terms of the two major nutrients, glucose and glutamine. At anaerobic conditions, glucose and glutamine have similar values to the cell, and the cost to synthesize most intermediates in terms of glucose is identical to the cost in terms of glutamine. At aerobic conditions, glucose is nearly twice as valuable to the cell as glutamine.
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PMID:Network analysis of intermediary metabolism using linear optimization. II. Interpretation of hybridoma cell metabolism. 159 97

To examine the interrelationships of proton compartmentation and ammoniagenesis, experiments were performed in tubules and mitochondria isolated from dog kidney cortex. Tubules were incubated in Krebs-Henseleit buffer at different pH (pHe), and cytosolic pH (pHi) was estimated with the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Mitochondrial pH (pHm) was determined simultaneously in intact tubules by use of dimethyloxazolidine-2,4-dione. Over the pHe range 6.9-7.7, pHi was similar in control and acidotic dogs and linearly related to pHe. At pHe 7.4 in control tubules. pHm was 7.78 +/- 0.07, and varied little over the pHe range of 7.0-7.7. The pH gradient across the mitochondrial membrane rose at acid pHe. pHm was more alkaline when estimated in tubules from acidotic dogs compared with controls. Ammonium and glucose productions from glutamine were inversely related to pHe and pHi in tubules from both control and acidotic animals and were higher in acidosis. In contrast, ammonium production by isolated mitochondria did not vary as pHe was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was inversely and glutaminase (PDG) flux was linearly related to pHe. Ammonium production was significantly greater in mitochondria from acidotic dogs because of accelerated flux through PDG but not GDH. The present study demonstrates significant difference between proton compartmentation and regulation of ammoniagenesis in kidneys from acidotic dog compared with rat.
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PMID:Regulation of glutamine metabolism in dog kidney cortex: effect of pH and chronic acidosis. 162 6

The LLC-PK1 renal epithelial cell line has been used as a model system to study renal ammoniagenesis and its regulation by metabolic acidosis in vitro. Experiments were performed on confluent LLC-PK1 epithelia grown for 10-14 days in conventional monolayer technique. After the medium pH was changed from 7.6 to 7.0 for 24-72 h by lowering the bicarbonate concentration in culture medium, LLC-PK1 cells responded with an adaptive increase in glutamine consumption and ammonia production. The rates of glutamine uptake and ammonia generation displayed a ratio of 1:1, i.e., 1 mol ammonia was produced per mole of glutamine consumed. Glutamine consumption and ammonia formation were paralleled by an equimolar production of L-alanine, indicating that transamination appears to be the main ammoniagenic pathway in LLC-PK1 cells. Analysis of the key enzymes of renal ammoniagenesis, phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH), revealed no changes in enzyme activities up to 72 h of adaptation. Alanine aminotransferase (ALT) activity in LLC-PK1 cells also remained unchanged during the adaptation period. Because transamination seems to play a crucial role in channeling the metabolic flux in LLC-PK1 ammoniagenesis, experiments were performed in which transamination was inhibited by (aminooxy)acetate (AOA). After incubation of control and pH 7.0-adapted LLC-PK1 cultures for 24-72 h in 0.2 mM AOA, no alanine production was found, but 2 mol of ammonia were formed per mole of glutamine consumed, again, without adaptive changes in PDG and GDH activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ammoniagenesis in LLC-PK1 cultures: role of transamination. 163 83

We found that cells of Saccharomyces cerevisiae have an elevated level of the NAD-dependent glutamate dehydrogenase (NAD-GDH; encoded by the GDH2 gene) when grown with a nonfermentable carbon source or with limiting amounts of glucose, even in the presence of the repressing nitrogen source glutamine. This regulation was found to be transcriptional, and an upstream activation site (GDH2 UASc) sufficient for activation of transcription during respiratory growth conditions was identified. This UAS was found to be separable from a neighboring element which is necessary for the nitrogen source regulation of the gene, and strains deficient for the GLN3 gene product, required for expression of NAD-GDH during growth with the activating nitrogen source glutamate, were unaffected for the expression of NAD-GDH during growth with activating carbon sources. Two classes of mutations which prevented the normal activation of NAD-GDH in response to growth with nonfermentable carbon sources, but which did not affect the nitrogen-regulated expression of NAD-GDH, were found and characterized. Carbon regulation of GDH2 was found to be normal in hxk2, hap3, and hap4 strains and to be only slightly altered in a ssn6 strain; thus, in comparison with the regulation of previously identified glucose-repressed genes, a new pathway appears to be involved in the regulation of GDH2.
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PMID:Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae. 165 57

Amino acid metabolism was examined in mitochondria from the lateral red muscle of a teleost (lake char, Salvelinus namaycush) and a nonteleost fish (bowfin, Amia calva). Isolated mitochondria oxidize a wide variety of substrates and have high respiratory control ratios. In both species, glutamine is oxidized more rapidly than any other amino acid. The rate of glutamine oxidation by bowfin mitochondria exceeds that of lake char mitochondria, and the bowfin displays correspondingly higher levels of mitochondrial phosphate-dependent glutaminase. It is suggested that amino acids in general, and glutamine in particular, are important oxidative substrates for nonteleost red muscle. The teleost red muscle, however, may rely on both glutamine and fatty acids as oxidative substrates. It appears that glutamate derived from glutamine is oxidized primarily via glutamate dehydrogenase, whereas exogenous glutamate is oxidized primarily via aspartate aminotransferase. Complete oxidation of glutamine may be accomplished in the absence of other substrates by conversion of glutamine-derived malate to pyruvate via malic enzyme. To assess the relative abilities of various tissues to synthesize and oxidize glutamine, the activities of glutamine synthetase and glutaminase were measured. The results of these studies indicate that the organization of glutamine metabolism of fish differs markedly from that in mammals.
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PMID:Glutamine metabolism in a holostean (Amia calva) and teleost fish (Salvelinus namaycush). 167 42

We analyzed the upstream region of the GDH2 gene, which encodes the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae, for elements important for the regulation of the gene by the nitrogen source. The levels of this enzyme are high in cells grown with glutamate as the sole source of nitrogen and low in cells grown with glutamine or ammonium. We found that this regulation occurs at the level of transcription and that a total of six sites are required to cause a CYC1-lacZ fusion to the GDH2 gene to be regulated in the same manner as the NAD-linked glutamate dehydrogenase. Two sites behaved as upstream activation sites (UASs). The remaining four sites were found to block the effects of the two UASs in such a way that the GDH2-CYC1-lacZ fusion was not expressed unless the cells containing it were grown under conditions favorable for the activity of both UASs. This complex regulatory system appears to account for the fact that GDH2 expression is exquisitely sensitive to glutamine, whereas the expression of GLN1, coding for glutamine synthetase, is not nearly as sensitive.
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PMID:Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae. 168 1

The reaction mechanism of Azospirillum brasilense glutamate synthase has been investigated by several approaches. 15N nuclear magnetic resonance studies demonstrate that the amide nitrogen of glutamine is reductively transferred to 2-oxoglutarate in an irreversible manner with no release of the transferred ammonia group into the medium. Identical results were obtained using thio-NADPH and acetylpyridine-NADPH, which are shown to be less efficient substrates of the enzyme than NADPH. Similarly, no exchange of the ammonia group being transferred with exogenous ammonium ion was observed during catalysis. The glutamate formed as the product of the iminoglutarate reduction was determined to be in the L configuration. The enzyme was also found to catalyze, under anaerobic conditions, the exchange of the 4proS H of NADPH with solvent both in the absence and in the presence of 2-oxoglutarate and glutamine. The reductive half-reaction is therefore a reversible segment of the overall irreversible amidotransferase reaction. 15N NMR studies also showed that the enzyme does not catalyze glutamate dehydrogenase/oxidase reactions or any observable glutaminase activity under neutral (pH 7.5) conditions. Glutaminase activity was also not observable with the reduced enzyme alone or in the presence of D-glutamate (a competitive inhibitor of glutamate synthase with respect to 2-oxoglutarate, with a Ki of about 11 microM) or with the oxidized enzyme in the presence of 2-oxoglutarate, D-glutamate, or NADP+. These data confirm species-dependent differences of A. brasilense glutamate synthase with respect to the enzyme from other sources.
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PMID:Mechanistic studies on Azospirillum brasilense glutamate synthase. 168 91

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine and alanine metabolism in lungs of septic rats. 168 36

Two pathways serve for assimilation of ammonia in Paracoccus denitrificans. Glutamate dehydrogenase (NADP+) catalyzes the assimilation at a high NH4+ concentration. If nitrate serves as the nitrogen source, glutamate is synthesized by glutamate-ammonia ligase and glutamate synthase (NADPH). At a very low NH4+ concentration, all three enzymes are synthesized simultaneously. No direct relationship exists between glutamate dehydrogenase (NADP+) and glutamate-ammonia ligase in P. denitrificans, while the glutamate synthase (NADPH) activity changes in parallel with that of the latter enzyme. Ammonia does not influence the induction or repression of glutamate dehydrogenase (NADP+). The inner concentration of metabolites indicates a possible repression of glutamate dehydrogenase (NADP+) by the high concentration of glutamine or its metabolic products as in the case when NH4+ is formed by assimilative nitrate reduction. No direct effect of the intermediates of nitrate assimilation on the synthesis of glutamate dehydrogenase (NADP+) was observed.
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PMID:Assimilation of ammonia in Paracoccus denitrificans. 168 63

Changes in midgut gland, muscle, and gill tissue nitrogen metabolic profiles studied in a penaeid prawn, Metapenaeus monoceros, following its exposure to sublethal concentrations of phosphamidon, methyl parathion, DDT, and lindane. In all the pesticide-exposed prawn tissues, ammonia levels were significantly increased and a shift in the nitrogen metabolism toward the synthesis of urea and glutamine was observed. Inhibition of glutamate oxidation to ammonia and alpha-ketoglutarate by glutamate dehydrogenase suggest a mechanism whereby hyperammonemia is reduced by minimizing the addition of further ammonia to the existing elevated ammonia. Aspartate (AAT) and alanine (AlAT) aminotransferases demonstrated an increase in their activity levels, suggesting gluconeogenesis. Pesticide-induced stress also seems to induce ammoniagenesis, which is due to increased deamination of purines. Mechanisms to detoxify the ammonia by enhancing the synthesis of urea and glutamine were observed in the tissues.
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PMID:Effects of sublethal concentrations of phosphamidon, methyl parathion, DDT, and lindane on tissue nitrogen metabolism in the penaeid prawn, Metapenaeus monoceros (Fabricius). 169 Jan 8


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