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)

Low molecular weight phosphoryl compounds, such as carbamoyl phosphate, 2,3-diphosphoglycerate and phytic acid protect, to different extents, mitochondrial and cytosolic proteins such as ornithine transcarbamoylase (OTC), carbamoyl phosphate synthetase (CPS), glutamate dehydrogenase (GDH) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH), from proteolytic inactivation (rat liver lysosomal extracts, pronase, elastase). Given the wide variety and common occurrence of low molecular weight reagents such as typified here, it seems that this kind of inhibition may be important in the regulation of protein turnover. Regulation of intracellular proteolysis can also occur via the proteolytic systems. Immunocytochemical procedures for mitochondrial enzymes (CPS, GDH, OTC), show intracellular homogeneity, but intercellular heterogeneity in rat liver, compatible with a role of the autophagic-lysosomal system in degrading these proteins. However, degradation of short-lived proteins occurs by other mechanisms. Using centrifugation of cultured cells, we find that the Golgi apparatus takes part in the degradation of these proteins, probably by controlling the traffic of proteins or proteases to the degradation site.
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PMID:Regulatory mechanisms of intracellular proteolysis in mammalian cells. 355 76

The different turnover rates of rat liver mitochondrial enzymes make autophagy unlikely to be the main mechanism for degradation of mitochondria. Although alternatives have been presented, hepatocyte heterogeneity has not been considered. Lighter hepatocytes isolated in a discontinuous Percoll gradient contain more glutamate dehydrogenase (GDH) (half-life 1 day) and a more active autophagic system than heavier hepatocytes. The latter contain more carbamoyl phosphate synthase (CPS) and ornithine carbamoyl transferase (OTC) (half-lives 8 days) but less lysosomal activity. As expected, isolated autophagic vacuoles contain, relative to the mitochondrial content, 3-times less OTC and CPS than GDH, probably reflecting a faster lysosomal engulfment of mitochondria in the light hepatocytes (which contain more GDH). These data may explain some of the half-life differences of the enzymes studied.
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PMID:Differences in the half-lives of some mitochondrial rat liver enzymes may derive partially from hepatocyte heterogeneity. 367 91

The effects of different substrates supporting respiration and glutamine-dependent citrulline synthesis from ornithine, ammonia, and bicarbonate by isolated hepatic mitochondria from Squalus acanthias (spiny dogfish) were determined. Highest rates of respiration were achieved with succinate, palmitoyl-CoA, and beta-hydroxybutyrate as oxidizable substrates. All acyl-CoAs tested (from C-2 to C-22) supported carnitine-dependent respiration at a substantial rate. Short-chain fatty acids did not support respiration. Ammonia required for citrulline synthesis could be formed from glutamate, or from leucine plus alpha-ketoglutarate which gives rise to glutamate by transamination, as the result of glutamate dehydrogenase activity, but the reaction was inhibited by succinate or other oxidizable substrates. Alanine or ornithine could not be substituted for leucine, suggesting that leucine may specifically activate glutamate dehydrogenase. Glutamate required for citrulline synthesis could be formed from alpha-ketoglutarate and ammonia as the result of glutamate dehydrogenase activity if succinate was present. Transamination of alpha-ketoglutarate with ornithine present in the reaction mixtures provided glutamate at a rapid rate whether or not succinate was present. These results are consistent with the view that hepatic dogfish mitochondria efficiently utilize acyl-CoAs derived from triglyceride stores in the liver to support respiration, glutamine-dependent citrulline synthesis from ammonia, and formation of ketone bodies as a major fuel for muscle.
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PMID:Support of respiration and citrulline synthesis by isolated hepatic mitochondria from Squalus acanthias by acyl-CoAs and other nitrogen-donating substrates. 381 53

Homogenates of insulin-producing tumoral cells catalyzed the phosphorylation of glucose, mannose, and fructose. The kinetics of phosphorylation at increasing glucose concentrations, the inhibitory effect of glucose 6-phosphate, and the comparison of results obtained with distinct hexoses indicated the presence of both low-Km hexokinase-like and high-Km enzymatic activities, the results being grossly comparable to those collected in normal pancreatic islets. Relative to protein content, the glucose-phosphorylating enzymatic activity was higher in tumoral than normal islet cells. The activity of other enzymes was either lower (glutamate dehydrogenase), moderately higher (phosphoglucomutase, lactate dehydrogenase) or considerably greater (ornithine decarboxylase) in tumoral than in normal islet cells. In intact tumoral cells, incubated under increasing glucose concentrations, the oxidation of D-[U-14C]glucose and the output of lactic and pyruvic acids reached a close-to-maximal value at 2.8 mM glucose. The ratios for glucose oxidation/utilization and lactate/pyruvate output were much lower in tumoral than in normal islet cells. Although glucose caused a modest increase in insulin output from the tumoral cells, this effect was saturated at a low glucose concentration (2.8 mM) and less marked than that of other secretagogues (e.g., L-leucine, L-ornithine, or forskolin). Thus, despite a close-to-normal enzymatic equipment for glucose phosphorylation, the tumoral cells displayed severe abnormalities in the metabolism and secretory response to this hexose. These findings point to regulatory mechanisms distal to glucose phosphorylation in the control of glucose metabolism in insulin-producing cells.
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PMID:Glucose metabolism in insulin-producing tumoral cells. 389 13

Parallel increases in the ornithine carbamyl transferase and glutamate dehydrogenase activities were observed in the serum of 22 Reye's syndrome patients. The increase in the activity of glutamate dehydrogenase was masked by a dialyzable inhibitor. It is proposed that the measurement of serum ornithine carbamyl transferase and glutamate dehydrogenase activities may be useful as an indicator of liver mitochondrial damage in Reye's syndrome.
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PMID:Serum glutamate dehydrogenase and ornithine carbamyl transferase in Reye's syndrome. 405 75

Treatment of rat liver mitochondria with digitonin followed by differential centrifugation was used to resolve the intramitochondrial localization of both soluble and particulate enzymes. Rat liver mitochondria were separated into three fractions: inner membrane plus matrix, outer membrane, and a soluble fraction containing enzymes localized between the membranes plus some solublized outer membrane. Monoamine oxidase, kynurenine hydroxylase, and rotenone-insensitive NADH-cytochrome c reductase were found primarily in the outer membrane fraction. Succinate-cytochrome c reductase, succinate dehydrogenase, cytochrome oxidase, beta-hydroxybutyrate dehydrogenase, alpha-ketoglutarate dehydrogenase, lipoamide dehydrogenase, NAD- and NADH-isocitrate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, and ornithine transcarbamoylase were found in the inner membrane-matrix fraction. Nucleoside diphosphokinase was found in both the outer membrane and soluble fractions; this suggests a dual localization. Adenylate kinase was found entirely in the soluble fraction and was released at a lower digitonin concentration than was the outer membrane; this suggests that this enzyme is localized between the two membranes. The inner membrane-matrix fraction was separated into inner membrane and matrix by treatment with the nonionic detergent Lubrol, and this separation was used as a basis for calculating the relative protein content of the mitochondrial components. The inner membrane-matrix fraction retained a high degree of morphological and biochemical integrity and exhibited a high respiratory rate and respiratory control when assayed in a sucrose-mannitol medium containing EDTA.
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PMID:Enzymatic properties of the inner and outer membranes of rat liver mitochondria. 569 70

1. Pentachloroethane and tetrachloroethylene were major metabolites of hexachloroethane in sheep.2. Concentrations of hexachloroethane, pentachloroethane and tetrachloroethylene were determined by gas-liquid chromatography in blood, bile, faeces, urine and tissues after oral administration of hexachloroethane emulsions to sheep.3. Increased blood concentrations of sorbitol dehydrogenase, glutamate dehydrogenase, and ornithine carbamoyl transferase were found to follow oral administration of hexachloroethane or pentachloroethane.4. The rate of bromsulphthalein transfer from liver cells to bile was found to decrease after oral administration of hexachloroethane.
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PMID:Some hepatotoxic actions of hexachloroethane and its metabolites in sheep. 580 42

1. Homogenates of liver or kidney from rat, mouse, dog and guinea pig formed ornithine from proline but not from glutamate. Rat kidney was most active in this reaction and was used for further studies. 2. The overall reaction was found to be catalysed by proline oxidase to yield glutamic gamma-semialdehyde, followed by transamination of this product with glutamate as catalysed by ornithine-keto acid aminotransferase. 3. The unfavourable equilibrium of the ornithine-keto acid aminotransferase reaction was overcome chiefly by glutamate dehydrogenase in the tissue, which removed the alpha-oxoglutarate produced, by reduction with endogenous ammonia and NADH. 4. Aspartate aminotransferase in these preparations also aided in the removal of alpha-oxoglutarate. In this case the overall reaction was driven also by the rapid decarboxylation of oxaloacetate. 5. No evidence could be found for a pathway of ornithine synthesis involving acylated intermediates as has been observed in some micro-organisms. 6. The rate of ornithine synthesis in homogenates of several rat tissues paralleled the activity of ornithine-keto acid aminotransferase in these tissues, indicating that this enzyme was rate-determining for the synthesis. 7. The possible influence of these reactions on urea synthesis is discussed.
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PMID:The formation of ornithine from proline in animal tissues. 604 97

Effects of norepinephrine on gluconeogenesis and ureogenesis from glutamine by hepatocytes from fasted rats were assessed. Comparisons were made to asparagine metabolism and to the effects of NH4Cl and dibutyryl cyclic AMP. With asparagine as substrate, aspartate content was very high but norepinephrine, dibutyryl cyclic AMP, or NH4Cl had little effect on gluconeogenesis or ureogenesis. Metabolism of asparagine could be greatly enhanced by the combination of oleate, ornithine, and NH4Cl. However, even under these conditions, asparatate content remained high, and norepinephrine and dibutyryl cyclic AMP had little influence on glucose or urea synthesis. With glutamine as substrate, aspartate content was much lower, but was greatly elevated by norepinephrine, dibutyryl cyclic AMP, or NH4Cl. Each of these effectors strongly stimulated glucose and urea formation from glutamine. NH4Cl stimulation was accompanied by an increased glutamate and decreased alpha-ketoglutarate content. This suggests the mechanism for NH4Cl stimulation is a near-equilibrium adjustment to ammonia by glutamate dehydrogenase and aspartate aminotransferase rather than a principal involvement of glutaminase. Although both norepinephrine and dibutyryl cyclic AMP lowered alpha-ketoglutarate to the same extent, norepinephrine more rapidly increased aspartate content and led to a smaller accumulation of glutamate than did dibutyryl cyclic AMP. Moreover, only norepinephrine led to a rapid increase in succinyl-CoA concentration. The catecholamine effect could not be explained by specific changes in cytosolic or mitochondrial redox states. The results suggest that alpha-ketoglutarate dehydrogenase is a site of catecholamine action in rat liver. Since purified alpha-ketoglutarate dehydrogenase is known to be Ca2+ stimulated and Ca2+ flux is involved in catecholamine action, these findings also suggest that mitochondrial Ca2+ is elevated by catecholamines.
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PMID:Glutamine metabolism of isolated rat hepatocytes. Evidence for catecholamine activation of alpha-ketoglutarate dehydrogenase. 609 58

The activities of a number of enzymes in rat liver have been measured at different times during adulthood and senescence and expressed as a percentage of maximal activity that can be attained after hormonal stimulation. Three different profiles can be detected. Type I profile shows decreasing activities during adolescence (1--3 months of age), increasing activities during adulthood (4--12 months of age) and relatively high activities thereafter. Enzymes of this group are carbamoyl-phosphate synthase and arginase; DNA content shows the same pattern. Type II profile shows decreasing activities during adolescence and relatively low activities thereafter. Enzymes of this group are tyrosine aminotransferase, glucose-6-phosphatase, and glucokinase. Type III profile shows relatively high activities during adolescence, adulthood and senescence. Enzymes of this group are ornithine transcarbamoylase, glutamate dehydrogenase and hexokinase. Some enzymes are constant with age in females, but slowly decrease in activity with age in males; decreasing levels of androgens and possibly also thyroid hormones can explain this decrease in males. Decreasing activities of carbamoyl-phosphate synthase and arginase during adolescence can be attributed to a depressant effect of gonadal hormones. The difference between relatively high and relatively low basal activities of enzymes in adult and senescent rats corresponds with their relatively long and short half-lives, respectively. This relation implicates a similar rate of synthesis of glucocorticosteroid hormone-dependent enzymes.
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PMID:Changes in the control of enzyme clusters in the liver of adult and senescent rats. 611 95


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