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)

1)The time course of changes in concentration of renal metabolites in response to a non-toxic load of NH4 as NH4 Cl or NH4HCO3 were measured in fasted rats. 2) Following a NH4Cl load, decrease of renal concentration of 2-oxoglutarate occurs but this change is delayed in relation to the peak of the blood ammonia concentration and persists after disappearance of the hyperammoniemia. 3) Following a NH4HCO3 load, the oxoglutarate concentration changes are less marked and more transient. 4) No close relationship between the mitochondrial free NAD/NADH ratio calculated from the glutamate dehydrogenase and the 3-hydroxybutyrate dehydrogenase systems were seen during alteration of the ammonia concentration. 5) Contrary to the observations in the liver under similar circumstances (BROSNAN, J.T. et al.: Biochem.J. 138, 453, 1974), no increase in kidney tissue or renal venous blood alanine or aspartate concentration are seen. 6) A constant infusion of NH4HCO3 resulted only in an increase in tissue and renal venous blood glutamine concentration. 7) The infusion of NH4 together with a carbon source (malate) resulted in a similar increase in tissue glutamine concentration and more striking increase in renal venous glutamine concentration. No accumulation of aspartate nor alanine were seen. 8) In vitro studies indicate that the net flux through both the aspartate aminotransferase and the glutamate dehydrogenase reactions is dependent on the concentration of the reactants as expected for a near-equilibrium system. 9) It is concluded that the kidney response to an ammonia load differs from that of the liver despite the existence of a similar network of near-equilibrium reactions of (1) a lack of local availability of oxaloacetate, (2) a lower activity of alanine aminotransferase, (3) a greater in vivo activity of glutamine synthetase.
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PMID:Effect of an ammonia load on the kidney near-equilibrium systems in the rat in vivo. 18 80

NAD-specific glutamate dehydrogenase (GDH-B) was induced in a wild-type strain derived of alpha-sigma 1278b by alpha-amino acids, the nitrogen of which according to known degradative pathways is transferred to 2-oxoglutarate. A recessive mutant (gdhB) devoid of GDH-B activity grew more slowly than the wild type if one of these amino acids was the sole source of nitrogen. Addition of ammonium chloride, glutamine, asparagine or serine to growth media with inducing alpha-amino acids as the main nitrogen source increased the growth rate of the gdhB mutant to the wild-type level and repressed GDH-B synthesis in the wild type. Arginine, urea and allantoin similarly increased the growth rate of the gdhB mutant and repressed GDH-B synthesis in the presence of glutamate, but not in the presence of aspartate, alanine or proline as the main nitrogen source. These observations are consistent with the view that GDH-B in vivo deaminates glutamate. Ammonium ions are required for the biosynthesis of glutamine, asparagine, arginine, histidine and purine and pyrimidine bases. Aspartate and alanine apparently are more potent inducers of GDH-B than glutamate. Anabolic NADP-specific glutamate dehydrogenase (GDH-A) can not fulfil the function of GDH-B in the gdhB mutant. This is concluded from the equal growth rates in glutamate, aspartate and proline media as observed with a gdhB mutant and with a gdhA, gdhB double mutant in which both glutamate dehydrogenases area lacking. The double mutant showed an anomalous growth behaviour, growth rates on several nitrogen sources being unexpectedly low.
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PMID:A mutant of Saccharomyces cerevisiae lacking catabolic NAD-specific glutamate dehydrogenase. Growth characteristics of the mutant and regulation of enzyme synthesis in the wild-type strain. 22 4

The sequential pattern of lipid accumulation and associated biochemical changes were studied in two commonly used experimental models of nutritional fatty liver in rats. Female rats were maintained for 8 weeks on high fat, low protein diets containing adequate methionine and choline, and drinking water ad libitum (Diet 1), or deficient in methionine and choline and containing 20% ethanol as a substitute for drinking water (Diet 2). Histologically, there was a progressive increase in liver lipids, mainly in the periportal areas. Occasional foci of liver cell necrosis with lipogranuloma formation occurred in areas of severe fatty change. These changes appeared earlier and were more marked in rats maintained on Diet 2. Electron micrographs revealed large lipid droplets in the liver cells, which sometimes contained myelin figures. The mitochondria were enlarged, distorted and appeared as amorphous structures with disorientated cristae in rats on Diet 1, whereas they had a condensed conformation in rats maintained on Diet 2. Rough endoplasmic reticulum was fragmented and degranulated particularly in rats on Diet 1, and smooth endoplasmic reticulum showed hyperplasia and vesiculation in rats on Diet 2. There was a progressive increase in the total liver lipids and triglycerides in both the groups of rats. This fatty change was accompanied by a significant increase in hepatic 3-hydroxybutyrate, acetoacetate, malate, 2-oxoglutarate, citrate, lactate, ammonia, glutamate, alanine and aspartate, and a significant decrease in oxaloacetate, urea and glucose concentrations. The mass action ratios for alanine aminotransferase, aspartate amino transferase, and glutamate dehydrogenase, generally moved in a parallel direction. Hepatic ATP content was considerably reduced accompanied by a decrease in [ATP]/[ADP] ratios and a significant increased in [lactate]/[pyruvate] and [3-hydroxybutyrate]/[acetoacetate] ratios. There was a corresponding decrease in the [NAD+]/[NADH] ratios both in the cytoplasmic and mitochondrial compartments. These biochemical changes were particularly severe in rats maintained on Diet 1 and Diet 2 for 8 weeks. There was a very good relationship between impaired mitochondrial and endoplasmic reticulum functions, redox and phosphorylation states, and the relevance of their changes to the fate of fatty liver cells.
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PMID:Lipid accumulation in the rat liver: a histological and biochemical study. 23

Using the semi-continuous cultivation technique we could establish that specifically in Streptomyces noursei JA 3890b during growth on a medium supplied with D,L-alanine, NH4+, and maize starch there are two different phenotypes of the organism and stationary states of metabolism, respectively. The expression of either the metabolic state I with an enhanced capacity to oxidative deamination of alanine via the NAD+-dependent alanaine dehydrogenase or the metabolic state 2 which may be characterized by the preferred use of ammonium ions via the NADP+-dependent glutamate dehydrogenase was shown to depend strongly on the conditions of inoculum cultivation. When the amino acid permeases were derepressed by cultivating the inoculum cells on amino acid media, probably due to the defective mechanism of negative feedback control of amino acid influx in this strain an abnormously high uptake of alanine was observed that, consequently, was correlated to the enhanced oxidation of this amino acid as well as to the intensive production of ammonia within the cell. This overproduction of cellular NH4+ seems to bring about the subsequent repression of biosynthetic glutamate dehydrogenase and so on the accumulation of ammonia autocatalytically may rise up (metabolic state I). On the other hand, if the influx of alanine was kept low and the NADH oxidation was less efficient, respectively, or when there was high cellular activity of glutamate dehydrogenase the level of ammonia never did exceed the respressory limit and, accordingly, the expression of the metabolic state 2 was observed. Switching-over of metabolic flux from the state 2 towards the state 1 can be brought about either by increasing the level of nitrogen sources in the medium or by adding buffers pH greater than 7.5. In contrast, decrease of cellular level of NH4+ was shown to induce the transition of metabolic state 1 into the state 2. This can be achieved not only by limitation of nitrogen source but also by adding different aminobenzoic acids and, alternatively, effectors of membrane function (short-chain alcohols), inhibitors of cytochrome oxidases (sodium azide, potassium cyanide), heavy metal (Fe++)-chelating agents (catechol, 2,5'-dipyridyl, o-phenanthroline), beta-alanine, and buffers pH less than 7. This suggests that these effectors are capable of preventing the abnormously high influx of amino acids as well as its wasteful catabolism within the cell of S. noursei JA 3890b. Therefore, it seems likely that by this way the aminobenzoic acids and similar effectors can diminish the catabolite repression or inhibition of secondary metabolism by cellular excess of some nitrogen compounds in good agreement with its well-known stimulatory action on the biosynthesis of the antibiotic nourseothricin in this strain.
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PMID:Regulative influence of o-aminobenzoic acid on the biosynthesis of nourseothricin in cultures of Streptomyces noursei JA 3890b. IV. Bistability of metabolism and the mechanism of action of aminobenzoic acids. 23 65

Methods are described in which liberation of ammonia from amino acid substrates by the D- and L-amino acid oxidases may be coupled with the NADH-dependent reductive amination of 2-oxoglutarate catalysed by exogenous glutamate dehydrogenase (L-glutamate: NAD oxidoreductase (deaminating), EC 1.4.1.2). The inhibition of D-amino acid oxidase (D-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.3) by ADP needed to activate and stabilise glutamate dehydrogenase was relieved by FAD, and the substrate was D-alanine at approximately 6-fold Km concentration. Neither FAD or FMN were required in the L-amino acid oxidase (L-amino acid:O2 oxidoreductase (deaminating), EC 1.4.3.2) assay; this utilised L-leucine as substrate in a concentration approximately 7-fold the Km value. The methods were reasonably sensitive and precise, and a linear relationship between activity and enzyme concentration prevailed up to an absorbance change of 0.050 per min. They have the advantage of being amenable to automation and to employment of fluorescence techniques should greater sensitivity be required.
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PMID:Coupled optical rate determinations of amino acid oxidase activity. 23 96

The effect of boseimycin on the in vitro activity and in vivo synthesis of alkaline phosphatase, aconitase and lactate, isocitrate, glutamate and alanine dehydrogenases was studied in Bacillus subtilis. At a subinhibitory concentration, synthesis of glutamate dehydrogenase was stimulated but alkaline phosphatase, lactate dehydrogenase and aconitase synthesis was inhibited. On the contrary, boseimycin inhibited slightly the activity of lactate dehydrogenase in cell-free extracts. Glutamate dehydrogenase and aconitase activities were not affected.
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PMID:Effect of boseimycin on some enzyme systems of Bacillus subtilis. 24 Jul 61

Two strains of Cyanidium caldarium, one able to utilize nitrate as a substrate, and the other not, were tested for the presence of enzymes of ammonia assimilation. The nitrate-assimilating strain exhibits glutamate dehydrogenase activity. By contrast, the other strain lacks glutamate dehydrogenase; it possesses high alanine dehydrogenase and L-alanine aminotransferase activities which suggest that this strain may incorporate ammonia through reductive amination of pyruvate and may form glutamate from 2-ketoglutarate by a transamination reaction with alanine. Neither strain reveals glutamate synthase activity. Both strains contain similar levels of glutamine synthetase.
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PMID:Observations on enzymes of ammonia assimilation in two different strains of Cyanidium caldarium. 24 91

The principal initial product of metabolism of 13N-labeled ammonium by Anabaena cylindrica grown with either NH4+ or N2 as nitrogen source is amide-labeled glutamine. The specific activity of glutamine synthetase is approximately half as great in NH4+-grown as in N2-grown filaments. After 1.5 min of exposure to 13NH4+, the ratio of 13N in glutamate to 13N in glutamine reaches a value of approximately 0.1 for N2- and 0.15 for NH4+-grown filaments, whereas after the same period of exposure to [13N]N2, that ratio has reached a value close to unity and is rising rapidly. During pulse-chase experiments, 13N is transferred from the amide group to glutamine into glutamate, and then apparently into the alpha-amino group of glutamine. Methionine sulfoximine, an inhibitor of glutamine synthetase, inhibits the formation of glutamine. In the presence of the inhibitor, direct formation of glutamate takes place, but accounts for only a few per cent of the normal rate of formation of that amino acid; and alanine is formed about as rapidly as glutamate. Azaserine reduces formation of [13N]glutamate approximately 100-fold, with relatively little effect on the formation of [13N]glutamine. Aminooxyacetate, an inhibitor of transaminase reactions blocks transfer of 13N to aspartate, citrulline, and arginine. We conclude, on the basis of these results and others in the literature, that the glutamine synthetase/glutamate synthase pathway mediates most of the initial metabolism of ammonium in A. cylindrica, and that glutamic acid dehydrogenase and alanine dehydrogenase have only a very minor role.
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PMID:The pathways of assimilation of 13NH4+ by the cyanobacterium, Anabaena cylindrica. 41 Aug 9

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

Cross-linking of the unimer of glutamate dehydrogenase from beef liver (consisting of six polypeptide chains each having a molecular weight of 56000) with dimethyladipimidate and subsequent analysis by sodium dodecylsulfate electrophoresis shows predominantly the trimeric species (molecular weight 168000). Treatment with dimethylimidates of other chain length yields significantly less trimeric species indicating that the amino groups being cross-linked are within a distance of about 0.85 nm. Comparison of the molar amount of incorporated [14C]dimethyladipimidate with the number of modified amino groups (determined with trinitrobenzenesulfonic acid) shows that although 8-9 of the 34 amino groups have reacted, only 2-3 of them are involved in cross-links. Reaction with dimethylimidates inactivates the enzyme. The loss of the activity is partly concomitant to cross-linking to the trimeric species and not simply due to the modification of essential lysine residues. This is supported by the fact that, although more lysine residues react with mono-functional methylimidates, the loss of activity is reduced. Purified chymotryptic and tryptic peptides of the radioactive-labeled trimeric species were subjected to sequence analysis. Six peptides containing 75% of the total label were identified: one involves the amino-terminal residue alanine-1 and the others involve lysine-105, lysine-154, lysine-269, lysine-358 and lysine-399. Quantitative analysis of the specific radioactivity of each peptide/mol lysine leads to the conclusion that only lysine-105, lysine-154, lysine-269 and lysine-358 participate in cross-links, lysine-269 and lysine-358, respectively, being at isologous and lysine-105 cross-linked with lysine-154 at heterologous contact domains of the enzyme. A model for the planar arrangement of the trimeric species in the quaternary structure of glutamate dehydrogenase is discussed. It includes both isologous and heterologous contact areas between the polypeptide chains.
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PMID:Studies of glutamate dehydrogenase. Analysis of quaternary structure and contact areas between the polypeptide chains. 55 96


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