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)

The pH dependence of the initial transient velocity of NADPH production during the burst phase of the oxidative deamination of L-glutamate by L-glutamate dehydrogenase (L-glutamate : NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3) and NADP+ has been measured by stopped-flow spectrophotometry. These studies provide evidence that the entire pH dependence below pH 8.26 arises from reaction steps contributing to V of the burst with an apparent pKa of 8.1 +/- 0.1. The data are consistent with a model in which the formation of the first enzyme-coenzyme-substrate ternary complex on the reaction path equilibrates rapidly and in which the pH-dependent steps are mechanistically close to and may include the catalytic hydrogen transfer itself. At pH 8.87, there is evidence that L-glutamate binds less tightly to the enzyme and to the enzyme-NADP+ complex than at lower pH values.
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PMID:The transient-state kinetics of L-glutamate dehydrogenase. pH-dependence of the burst rate parameters. 1 5

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

The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations.
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PMID:Effects of dimethyl sulfoxide on subunit proteins. 23 13

We have studied the effects of ammonium acetate on the transient "burst" phase of the oxidation of L-glutamate by glutamate dehydrogenase. Two measurable changes are observed in the "burst" phase as ammonium acetate concentration is increased: (i) an increase in the apparent first-order rate constant, kapp, and (ii) a decrease in the amplitude of the absorbance change measured at 320 nm. The increase in kapp shows a hyperbolic dependence on ammonium acetate concentration and is independent of glutamate concentration. The results demonstrate the existence of an intermediate immediately following hydrogen transfer. The intermediate contains enzyme, reduced coenzyme, ammonia, and alpha-ketoglutarate moieties and is in equilibrium with the known complex consisting of enzyme, reduced coenzyme, and alpha-ketoglutarate. At high concentrations of ammonium acetate, the equilibrium favors the ammonia containing complex.
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PMID:Effect of ammonia on the glutamate dehydrogenase catalyzed oxidative deamination of L-glutamate: production of an ammonia-containing intermediate in the "burst" phase. 65 77

Isolated mitochondria of pigeon and guinea pig liver were subjected to zonal centrifugation. With pigeon liver mitochondria there was uniform distribution of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, aspartate aminotransferase and glutamate dehydrogenase activities. Guinea pig liver mitochondria demonstrated two pyruvate carboxylase and phosphoenolpyruvate carboxykinase maxima but only one maximum with aspartate aminotransferase, malate dehydrogenase and glutamate dehydrogenase. Mitochondrial enzyme levels in rat, pigeon and guinea pig indicate different roles of certain gluconeogenic enzymes in the transport of carbon and hydrogen in and out of mitochondria.
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PMID:The relationship between mitochondrial heterogeneity and gluconeogenesis in liver mitochondria of the rat, pigeon and guinea pig. 119 37

The dinucleotide binding beta alpha beta motif in the crystal structures of seven different enzymes has been analysed in terms of their three-dimensional structures and primary sequences. We have identified that the hydrogen bonding of the adenine ribose to the glycine-rich turn containing the fingerprint sequence GXGXXG/A occurs via a direct or indirect mechanism, depending on the nature of the fingerprint sequence but independent of coenzyme specificity. The major determinant of the type of interaction is the nature of the residue occupying the last position of the above fingerprint. In the NAD(+)-linked dehydrogenases, an acidic residue is commonly used to form important hydrogen bonds to the adenine ribose hydroxyls and, hitherto, this residue has been thought to be an indicator of NAD+ specificity. However, on the basis of the three-dimensional structure of the NAD(+)-linked glutamate dehydrogenase (GDH) from Clostridium symbiosum we have demonstrated that this residue is not a universal requirement for the construction of an NAD+ binding site. Furthermore, considerations of sequence homology unambiguously identify an equivalent acidic residue in both NADP+ and dual specificity glutamate dehydrogenases. The conservation of this residue in these enzymes, coupled to its close proximity to the 2' phosphate implied by the necessary similarity in three-dimensional structure to C. symbiosum GDH, implicates this residue in the recognition of the 2' phosphate either via water-mediated or direct hydrogen-bonding schemes. Analysis of the latter has led us to suggest that two patterns of recognition for the 2' phosphate group of NADP(+)-binding enzymes may exist, which are distinguished by the ionization state of the 2' phosphate.
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PMID:Structural consequences of sequence patterns in the fingerprint region of the nucleotide binding fold. Implications for nucleotide specificity. 145 69

The three-dimensional crystal structure of the NAD(+)-linked glutamate dehydrogenase from Clostridium symbiosum has been solved to 1.96 A resolution by a combination of isomorphous replacement and molecular averaging and refined to a conventional crystallographic R factor of 0.227. Each subunit in this multimeric enzyme is organised into two domains separated by a deep cleft. One domain directs the self-assembly of the molecule into a hexameric oligomer with 32 symmetry. The other domain is structurally similar to the classical dinucleotide binding fold but with the direction of one of the strands reversed. Difference Fourier analysis on the binary complex of the enzyme with NAD+ shows that the dinucleotide is bound in an extended conformation with the nicotinamide moiety deep in the cleft between the two domains. Hydrogen bonds between the carboxyamide group of the nicotinamide ring and the side chains of T209 and N240, residues conserved in all hexameric GDH sequences, provide a positive selection for the syn conformer of this ring. This results in a molecular arrangement in which the A face of the nicotinamide ring is buried against the enzyme surface and the B face is exposed, adjacent to a striking cluster of conserved residues including K89, K113, and K125. Modeling studies, correlated with chemical modification data, have implicated this region as the glutamate/2-oxoglutarate binding site and provide an explanation at the molecular level for the B type stereospecificity of the hydride transfer of GDH during the catalytic cycle.
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PMID:Subunit assembly and active site location in the structure of glutamate dehydrogenase. 155 82

The metabolism of a typical North American diet yields a net acid load. Hydrogen ions are removed from the body after combining with bicarbonate to form CO2. This leaves the body with a deficit of bicarbonate. The role of the kidney is to add 'new' bicarbonate to the body. It does so primarily by synthesizing NH4+ plus bicarbonate while making NH4+ an end-product of metabolism (excreting it in the urine). Production of NH4+ occurs primarily in proximal convoluted tubule cells. Although several possible pathways can do this, the primary one stimulated by chronic metabolic acidosis is the glutaminase/glutamate dehydrogenase one. The upper limit on this pathway is set by energy turnover considerations. This, in effect, means control by renal work (sodium reabsorption) and fuel competitions (availability of fat-derived fuels).
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PMID:Ammonium metabolism: emphasis on energy considerations. 228 91

Chemiluminometric methods are described for the automated flow injection analysis of NADPH and NADH using an immobilized enzyme column reactor and serum magnesium. This application is for the clinical analysis of NADPH and NADH. The reactor for NADPH and NADH contains immobilized L-glutamate dehydrogenase and L-glutamate oxidase, and that for serum magnesium immobilized hexokinase, glucose-6-phosphate dehydrogenase, L-glutamate dehydrogenase and L-glutamate oxidase. When the sample is introduced into the four-enzyme bioreactor, hydrogen peroxide is produced in proportion to the concentration of serum magnesium by the successive reactions. A co-immobilized hexokinase/glucose-6-phosphate dehydrogenase/glutamate dehydrogenase column reactor gave better efficiency compared with an enzyme column which was prepared by packing co-immobilized hexokinase/glucose-6-phosphate dehydrogenase and immobilized glutamate dehydrogenase to make two layers. Magnesium in serum was determined with 1 microL of the sample without carry-over and for an assay time of approximately 15 s. The present method is sensitive (detection limit 0.1 nmol) because Mg2+ is recycled in a column, and gives perfect linearity of the data up to 3.0 mmol/L with satisfactory precision, reproducibility, and accurate reaction recoveries.
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PMID:A chemiluminometric method for NADPH and NADH using a two-enzyme bioreactor and its application to the determination of magnesium in serum. 238 94

We have established a simple procedure for the in situ analysis of stereospecificity of an NAD(P)-dependent dehydrogenase for C-4 hydrogen transfer of NAD(P)H by means of glutamate racemase [EC 5.1.13] and glutamate dehydrogenase [EC 1.4.1.3]. Glutamate racemase inherently catalyzes the exchange of alpha-H of glutamate with 2H during racemization in 2H2O. When the reactions of glutamate racemase and glutamate dehydrogenase, which is pro-S specific for the C4-H transfer of NAD(P)H, are coupled in 2H2O, [4S-2H]-NAD(P)H is exclusively produced. Therefore, if 1H is fully retained at C-4 of NAD(P)+ after incubation of a reaction mixture containing both the enzymes and a dehydrogenase to be tested, the stereospecificity of the dehydrogenase is the same as that of glutamate dehydrogenase. When the C4-H of NAD(P)+ is exchanged with 2H, the enzyme to be examined is different from glutamate dehydrogenase in stereospecificity. Thus, we can readily determine the stereospecificity by 1H-NMR measurement of NAD(P)+ without isolation of the coenzymes and products.
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PMID:Enzymatic in situ analysis by 1H-NMR of the hydrogen transfer stereospecificity of NAD(P)+-dependent dehydrogenases. 257 93


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