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)

1. The metabolism and metabolic effects of 3-phenylpyruvate were examined in rat pancreatic islets. 2. Islet homogenates catalysed transamination reactions between 3-phenylpyruvate and L-glutamate, L-leucine, L-norleucine or L-valine. 3-Phenylpyruvate failed to activate glutamate dehydrogenase. 3. 3-Phenylpyruvate rapidly entered into islet cells, was extensively converted into phenylalanine but slowly oxidized. 4. The conversion of phenylpyruvate into phenylalanine coincided with a fall in the content of several amino acids (especially glutamate and aspartate) in the islets and incubation medium, the accumulation of 2-oxoglutarate and a modest fall in the NH4+ production rate. 5. 3-Phenylpyruvate failed to affect 14CO2 output from islets prelabelled with [U-14C]palmitate, but augmented 14CO2 output from islets prelabelled or incubated with L-[U-14C]glutamine. 6. In the presence of L-glutamine, 3-phenylpyruvate augmented the ATP/ADP ratio and NAD(P)H islet content, and caused a rapid and sustained decrease in the outflow of radioactivity from islets prelabelled with [2-3H]adenosine. 7. These data support the view that the insulin-releasing capacity of 3-phenylpyruvate coincides with an increase in the catabolism of endogenous amino acids acting as 'partners' in transamination reactions leading to the conversion of 3-phenylpyruvate into phenylalanine.
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PMID:Mechanism of 3-phenylpyruvate-induced insulin release. Metabolic aspects. 640 83

The effects of ATP and GTP on the activities of ox liver and brain glutamate dehydrogenase were determined in the absence and presence of added Mg2+ ions. Although GTP was an inhibitor of the enzyme reaction assayed in the direction of NAD+ reduction, the magnesium complex of this nucleotide had no effect on the activity. Similarly the magnesium complex of ATP was without effect on the activity of the enzyme although the free nucleotide was an activator. These results suggest that it is important to take account of magnesium complex formation when considering the regulatory actions of these nucleotides.
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PMID:The effects of magnesium ions on the interactions of ox brain and liver glutamate dehydrogenase with ATP and GTP. 646 7

The digitonin method for the study of cellular compartmentation in mitochondrial and cytosolic fractions was applied to Ehrlich ascites tumor cells. The volume of mitochondrial and cytosolic water spaces are calculated to be 1.62 microliter/30 x 10(6) cells respectively, by the technique of 3H2O permeable and (14C)-sucrose impermeable spaces. The validity of the methods was tested by the distribution of cytosolic (lactate dehydrogenase) and mitochondrial (citrate synthase and glutamate dehydrogenase) marker enzymes. As occurs in normal hepatic cells, an asymmetric distribution of ATP and ADP was observed. The ATP/ADP ratio in the cytosolic fraction was 7 times higher than in the mitochondrial fraction.
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PMID:Cellular compartmentation of Ehrlich ascites tumor cells. 653 6

Carbamyl phosphate synthase-I and glutamate dehydrogenase both form a complex with mitochondrial aspartate aminotransferase. Instead of these two enzymes competing for the aminotransferase, carbamyl phosphate synthase-I enhances glutamate dehydrogenase-aminotransferase interaction. This suggests that a complex can be formed between all three enzymes. Since this complex is stable in the presence of substrates and modifiers of the three enzymes, it could conceivably convert NH+4 produced from aspartate into carbamyl phosphate. Furthermore, since carbamyl phosphate synthase-I is the predominant protein in liver mitochondria, it could play a major role in placing the aminotransferase and glutamate dehydrogenase in close proximity. Malate removes glutamate dehydrogenase from the tri-enzyme complex and thus could play a role in determining whether glutamate dehydrogenase interacts with carbamyl phosphate synthase-I or is available to participate in reactions with the Krebs cycle. Palmitoyl-CoA has a high affinity for both carbamyl phosphate synthase-I and glutamate dehydrogenase. ATP and malate which, respectively, decrease and enhance binding of palmitoyl-CoA to glutamate dehydrogenase, respectively decrease and enhance the ability of this enzyme to compete with carbamyl phosphate synthase-I for palmitoyl-CoA. Since carbamyl phosphate synthase-I is present in high levels in liver mitochondria and has a high affinity for palmitoyl-CoA, it could play a major role as a reservoir for palmitoyl-CoA.
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PMID:Interactions between carbamyl phosphate synthase-I-mitochondrial aspartate aminotransferase and palmitoyl-CoA. 671 33

1) In the present study the influence of sucrose and mannitol-based isolation media on the degree of functional preservation of rat liver mitochondria has been investigated. Apparently intact mitochondria conventionally prepared with a 0.3M sucrose medium displayed significantly lower rates of state-3 respiration, pyruvate carboxylation, ATP hydrolysis and thiol group production than mitochondria prepared from the same livers with mannitol. 2) Extracts from the latter, furthermore, showed a significantly higher activity of succinate dehydrogenase activity, whereas no difference in glutamate dehydrogenase activity was demonstrable. 3) The low activities apparent with the sucrose medium could be brought to the level of the mannitol medium by the addition of potassium phosphate (4mM). A similar effect was exerted by K2SO4, whereas KCl and the respective sodium salts were significantly less effective. 4) Sucrose-prepared mitochondria display decreased contents of metabolites such as ATP, glutamate, citrate and malate. 5) Comparative studies with a variety of carbohydrates indicated that isolation media based on disaccharides are inferior to those based on monosaccharides in the preparation of functionally intact mitochondria from rat liver. 6) The results reported herein appear to be of general interest as sucrose-prepared mitochondria have been employed in the past in a great number of studies and are still widely used at present.
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PMID:Influence of isolation media on the preservation of mitochondrial functions. 686 77

The ratio of free ATP to free ADP in the mitochondrial matrix [( ATPf]/[ADPf]) has been measured in suspensions of isolated mitochondria under conditions of active phosphorylation of extramitochondrial ADP. These measurements utilized phosphoenolpyruvate carboxykinase which is present in the matrix of mitochondria from the livers of guinea pigs, chickens, and pigeons. Mitochondria isolated from these sources also contain nucleoside diphosphate kinase, malate dehydrogenase, and glutamate dehydrogenase or 3-OH-butyrate dehydrogenase. Together these enzymes catalyze the synthesis of phosphoenolpyruvate and CO2 from oxaloacetate with oxidative phosphorylation as an energy source. These reactions have been shown to be fully reversible in suspensions of mitochondria isolated from the above sources. With oxidative phosphorylation as the source of ATP, phosphoenolpyruvate was synthesized from malate and conversely addition of phosphoenolpyruvate, ADP, and CO2 led to synthesis of malate and ATP. The forward and reverse reactions were allowed to continue until the rate of change of metabolite concentrations was minimal and then the latter were measured. The intramitochondrial [Mg-ATPf]/[MgADPf] was calculated from the equilibrium constants for the reactions and the measured steady state concentrations of the metabolites in both the intra- and extramitochondrial spaces. The value of the intramitochondrial [MgATPf]/[MgADPf] was found to exceed the extramitochondrial value (adjusted to the same free Mg2+ concentration) by a factor (+/- S.E.) of 0.83 +/- 0.22 (n = 17) for the forward reaction and 1.81 +/- 0.54 (n = 11) for the reverse reaction. It is concluded that the adenine nucleotide translocase catalyzes electroneutral exchange of ATP for ADP and that this reaction does not contribute significantly to the energetics of mitochondrial oxidative phosphorylation.
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PMID:Evaluation of the relationship between the intra- and extramitochondrial [ATP]/[ADP] ratios using phosphoenolpyruvate carboxykinase. 688 88

1. The coenzyme preference of bovine liver glutamate dehydrogenase (GDH) was probed using dual wavelength spectroscopy and pairing the thionicotinamide analogues, S-NAD or S-NADP (which have absorbance maxima at 400 nm), with the natural coenzymes, NADP or NAD. 2. S-NAD and S-NADP were found to be good alternate substrates for GDH: the apparent Km's for the thioderivatives were similar to those of the corresponding natural coenzymes, the apparent Km's for glutamate were unaltered by the substitution of the thioderivatives, and the effects of inhibitors and activators on S-NAD or S-NADP kinetics were qualitatively the same as those found for NAD or NADP, respectively. 3. Dual wavelength assays paired NAD and S-NADP or S-NAD and NADP to study the simultaneous reduction of the two coenzymes. Conditions of increasing glutamate concentrations produced differential effects on the rates of the NAD vs NADP reactions, the result, with either nucleotide pair, promoting the NADP linked reaction. 4. Activators and inhibitors of the GDH reaction also showed differential effects upon the NAD vs NADP linked reaction rates in the dual wavelength assay. ADP and leucine, which activate both the NAD and the NADP linked reactions in single coenzyme assays, preferentially activate the NADP or S-NADP linked reactions in the dual nucleotide assays. GTP produced greater inhibition of the NAD or S-NAD linked reactions than of the NADP or S-NADP reactions while ATP inhibited NAD or S-NAD reactions and activated NADP or S-NADP reactions. The net effect of all metabolite modulators was to promote the NADP linked reaction by decreasing the activity ratios, v(NAD)/v(S-NADP) or v(S-NAD)/v(NADP). 5. The results are consistent with the suggestion that NADP is the preferred coenzyme for the oxidative deamination of glutamate by GDH even though the enzyme is capable of utilizing either coenzyme in vitro.
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PMID:Regulation of coenzyme utilization by bovine liver glutamate dehydrogenase: investigations using thionicotinamide analogues of NAD and NADP in a dual wavelength assay. 717 89

Ornithine metabolism is coupled to oxidative phosphorylation in isolated rat liver mitochondria. The pathway involving ornithine: alpha-ketoglutarate transaminase (OKT), glutamic semialdehyde dehydrogenase (GSDH), and glutamate dehydrogenase (GDH) with cycling of alpha-ketoglutarate-glutamate at the OKT reaction appears to be involved. Ornithine may be utilized by this pathway to sustain ATP levels during mitochondrial energy-deficiency states with resultant decreased urea-cycle flux and increased ammonia production. This pathophysiologic mechanism suggests that hyperammonemia is a consequence of an energy-deficiency state. Therapy directed toward alleviating the energy-deficiency state may be more beneficial than efforts to reduce ammonia levels.
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PMID:Urea cycle regulation: I. Coupling of ornithine metabolism to mitochondrial oxidative phosphorylation. 718 96

1. Protein-free extracts of isolated rat-liver mitochondria contain 5.17 +/- 0.19 nmol ammonia/mg protein [cf. Harris, E. J. and Bassett, D. J. (1971) FEBS Lett. 19, 214-217]. 2. The ammonia found in the protein-free extracts does not originate from lysosomes contaminating the mitochondrial preparation. 3. When isolated mitochondria are incubated with ornithine, 14CO2 and a source of ATP a small amount of citrulline is formed. This amount is stoichiometrically equivalent to the ammonia that disappears from the extramitochondrial space, whereas the amount of ammonia found in the protein-free extracts of the mitochondria remains unchanged. Similar results were obtained when the reductive amination of 2-oxoglutarate was used as an ammonia-consuming reaction. 4. When isolated mitochondria are incubated under conditions such that the glutamate dehydrogenase and 3-hydroxybutyrate dehydrogenase reactions reach equilibrium, the thermodynamically active concentration of ammonia is not equal to the concentration measured in the protein-free extracts. 5. About 80% of the ammonia found in protein-free extracts of rat-liver mitochondria is derived from a component or components with a molecular weight of greater than or equal to 50,000. 6. Protein-free extracts of isolated rat-liver cells contain considerable amounts of ammonia. After digitonin fractionation this ammonia is found in the protein-free extract of the particulate fraction. 7. It is concluded that the ammonia found in protein-free extracts of rat-liver tissue is derived from a component or components in the mitochondria and is released during deproteinization.
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PMID:Origin of the ammonia found in protein-free extracts of rat-liver mitochondria and rat hepatocytes. 743 58

1. Addition of 4-dimethylaminophenol (DMAP) to suspensions of isolated rat kidney tubules increased extracellular lactate dehydrogenase (LDH) at concn. which did not markedly affect gluconeogenesis. ATP content was also decreased by DMAP but this did not occur until the membrane became permeable to LDH. There was no similar leakage of the mitochondrial enzyme glutamate dehydrogenase. 2. After i.v. injection of DMAP to rats in doses which did not inhibit gluconeogenesis, kidney glutathione was decreased and the urinary LDH was increased. DMAP was irreversibly bound to tissue in rat, with the highest binding in the kidney. The highest binding occurs in those tissues in which DMAP causes necrosis. 3. In isolated rat hepatocytes, DMAP caused toxic effects which were similar but less extensive than occur on addition of DMAP to kidney tubules. The formation of acid-soluble metabolites was higher in isolated rat hepatocytes (20 nmol/mg protein) than in rat kidney tubules (4 nmol/mg protein). DMAP-glucuronide and DMAP-sulphate comprised the major acid-soluble metabolites in both preparations; conjugates of DMAP with glutathione or cysteine were also found.
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PMID:Effects of 4-dimethylaminophenol in rat kidneys, isolated rat kidney tubules and hepatocytes. 744 27


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