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. Hyperuricemia is common among the gouty relatives as reported by others (8-11). It is of interest to note that serum urate fluctuates periodically. Hyperuricemia is not necessarily maintained in a steady state throughout the years. Thus a single determination of serum uric acid can be misleading. 2. Development of gout from asymptomatic hyperuricemia is often correlated with the degree of hyperuricemia as observed from population or family studies (12-14). The data presented indicate that unequivocal hyperuricemia is more often accompanied by excessive excretion of uric acid, diminished excretion of ammonia and abnormally high plasma glutamic acid. All are undoubtedly important risk factors for gout. 3. The elevated glutamate could be due to a deficiency of glutamic dehydrogenase, as postulated by Pagliara and Goodman (15). In presence of intracellular accumulation of glutamate in glutamic dehydrogenase deficiency, renal production of ammonium may be reduced due to its inhibitory action on glutaminase 1. As a result of a renal block of ammonia formation, the glutamine in surplus may be diverted for uric acid synthesis. 4. Long-term studies indicate serum urate in most hyperuricemia relatives of gout can be modified by environmental factors, such as diet, weight and changes of life style. When hyperuricemia is under better control, the potential hazard of developing symptomatic gout may be circumvented.
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PMID:The natural history of hyperuricemia among asymptomatic relatives of patients with gout. 742 21

A new procedure for the analysis and detection of phosphate-activated glutaminase (EC 3.5.1.2) by native electrophoresis has been developed. The method is based on the in situ detection of glutaminase activity in two different systems of native polyacrylamide gradient gels, containing 3-(3-cholamidopropyl)-dimethyl-ammonio-1-propane sulfonate (CHAPS) or Triton X-100 as nondenaturant detergents. Crude Triton X-100 extracts of mitochondria were resolved by electrophoresis. The enzyme was specifically revealed by incubation of the gel with glutamine and coupling the oxidation of the glutamate formed to the reduction of a tetrazolium dye, in the presence of glutamate dehydrogenase trapped in a 1% agar solid overlay. Both Ehrlich ascitic cell and mouse kidney glutaminases were resolved by native electrophoresis and specifically detected with the activity staining. Moreover, the redox-cycling staining was tested in solution, showing linearity with the amount of glutamate or glutaminase activity present. The method described could be a useful tool for native polyacrylamide gel electrophoresis of membrane proteins.
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PMID:Native polyacrylamide gel electrophoresis of membrane proteins: glutaminase detection after in situ specific activity staining. 768 75

In renal ammoniagenesis, two major pathways of glutamine metabolism have been described: (i) intracellular metabolism by phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase and (ii) extracellular metabolism by phosphate-independent glutaminase. The latter has been identified as the hydrolytic activity of the apically membrane-bound gamma-glutamyl transpeptidase (gamma-GT). The growth properties of cultured renal epithelia enable the study of in vitro extracellular metabolic properties occurring at the apical epithelial surface in the culture dish. Therefore, confluent epithelia of the LLC-PK1 renal epithelial cell line were used to elucidate the role of extracellular (apical) hydrolysis of glutamine by gamma-GT in LLC-PK1 ammonia production. To distinguish between intra- and extracellular metabolism of glutamine, confluent LLC-PK1 epithelia were incubated with either D-glutamine as substrate, which cannot be metabolized intracellularly by PDG, or with L-glutamine and hippurate to stimulate, and AT-125 (acivicin) to inhibit gamma-GT activity, respectively. In addition, cellular uptake of the glutamate, extracellularly formed by gamma-GT, was inhibited by D-aspartate. D-Glutamine (2 mM) did not increase ammonia formation above endogenous production levels, indicating the negligible role of extracellular hydrolysis of glutamine by gamma-GT. After modulating gamma-GT activity by hippurate or AT-125, almost identical ammonia production rates were found within the various experimental protocols, further confirming that extracellular metabolism of glutamine does not significantly contribute to LLC-PK1 ammoniagenesis.
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PMID:Ammoniagenesis in renal cell culture. Lack of extracellular ammoniagenesis at the apical surface of LLC-PK1 epithelia. 768 42

Rat hippocampal slices preloaded with D-[3H]aspartate, a non metabolizable analogue of L-glutamate, were superfused with artificial CSF. Depolarization was induced by 53.5 mM K+, in the presence of Ca2+ (1.3 mM) or Mg2+ (5 mM) to determine the Ca2+ dependent release. Haloperidol added in the superfusion medium at 100 microM reduced by about 60% the Ca2+ dependent release of D-[3H]aspartate. This drug at 20 microM or 100 microM inhibited the non-activated glutamate dehydrogenase (GDH) but had no effect on GDH activated by ADP (2 mM) or leucine (5 mM). In addition no effect was observed on phosphate activated glutaminase (PAG) in the presence either of 20 mM or 5 mM phosphate. These results indicate that the effect of haloperidol is exerted on presynaptic mechanisms regulating neurotransmitter release.
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PMID:Haloperidol reduces K(+)-evoked Ca(2+)-dependent D-[3H]aspartate release from rat hippocampal slices. 773 54

The ammonia concentration and changes in the activity of ammonia metabolizing enzymes in the brain tissue during ischemia/reperfusion were investigated in rats. During ischemia (0.5 h) we found a statistically significant increase in brain ammonia concentration and a significant decrease in glutamate dehydrogenase activity. After 1 h of reperfusion, a further accumulation of ammonia concentration was observed. Furthermore, the brain glutamine syntethase and glutamate dehydrogenase were decreased, whereas the brain glutaminase activity was increased. The causes for the changed activities of some ammonia metabolizing enzymes in brain after ischemia/reperfusion have been discussed.
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PMID:Accumulation of ammonia and changes in the activity of some ammonia metabolizing enzymes during brain ischemia/reperfusion injury in rats. 780 37

Glutamine is actively metabolized in human platelets, representing a preferential mitochondrial oxidative substrate in these cells. The primary importance of this metabolic route of glutamine is further confirmed here by the observation that platelet glutaminase activity is entirely represented by the phosphate dependent glutaminase or glutaminase I, most probably localized in the mitochondrial platelet fraction and classified by kinetic analysis as a kidney-type form. The following step of the glutamine metabolizing pathway, allowing the entrance of the amino acid skeleton carbons in the Krebs cycle, might be catalyzed by both glutamate dehydrogenase and aspartate transaminase, the first being entirely mitochondrial and the latter 65% mitochondrial. We also investigated platelets for the presence of one or more specific transport systems involved in glutamine uptake and we present the first evidence for two glutamine transport systems in human platelets that by inhibition analysis appear to share characteristics with the Na(+)-dependent ASC system and the Na(+)-independent L system for dipolar amino acid uptake. Both systems display affinity characteristics for glutamine in the range of plasma glutamine concentration and may thus have physiological relevance for the uptake of the amino acid in these cells.
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PMID:Glutamine transport and enzymatic activities involved in glutaminolysis in human platelets. 782 6

Phosphate depletion (PD) in vivo causes a sundry of abnormalities in pancreatic islets including a rise in cytosolic calcium, low ATP content, reduced Ca2+ ATPase and Na(+)-K+ ATPase activity, and impaired insulin secretion in response to glucose or potassium. L-Leucine is a strong secretagogue that triggers insulin secretion by deamination to alpha-ketoisocaproic acid (KIC) and the subsequent metabolism of the latter to ATP and by the activation of glutamate dehydrogenase (GLDH), which acts on glutamate to generate alpha-ketoglutarate, the metabolism of which results in ATP production. The generation of ATP triggers events that lead to insulin secretion. It is not known whether PD impairs leucine-induced insulin secretion, and the cellular derangements that are involved in such an abnormality are not defined. These issues were studied in PD rats and in pair-weighed normal animals as controls. D-Leucine uptake by islets from PD rats is normal, but both leucine- and KIC-induced insulin secretions are impaired and the activity of branched-chain keto acid dehydrogenase, which facilitates the metabolism of KIC, is reduced. Both leucine and 2-aminobicyclo (2-2-1) haptene failed to stimulate GLDH and to augment the generation of alpha-ketoglutarate in the islets of PD rats. Also, the concentration of basal alpha-ketoglutarate was significantly higher in the islets of PD rats, suggesting that its metabolism is impaired. In addition, the activity of glutaminase is significantly reduced, an abnormality that would result in decreased production of glutamate, the substrate for GLDH. The data show that PD impairs leucine-induced insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphate depletion impairs leucine-induced insulin secretion. 787 37

Changes in protein and mRNAs for enzymes of glutamine metabolism were determined in rat kidney cortex at different times after induction of NH4Cl acidosis. After NH4Cl, phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 16-fold by 10 h (P < 0.05) and then returned to control levels by 30 h. In situ hybridization (ISH) showed that PEPCK mRNA was confined to medullary rays; after NH4Cl, expression of PEPCK expanded throughout the cortex, reaching a maximal intensity at 10 h. Phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH) mRNAs increased 8- and 2.6-fold, respectively (both P < 0.05), by 10 h before decreasing; the increased expression was confirmed by ISH. Immunohistochemistry showed that increased PEPCK, PDG, and GDH protein occurred at variable times after the rise in mRNAs. The increase was confined to proximal tubules and was sustained, a finding noted also by Western blot analysis. In contrast, glutamine synthase protein and mRNA, confined to deep cortex and outer medullar, did not change after NH4Cl. These studies reveal striking changes in PEPCK and PDG mRNAs in rat renal cortex during acidosis. The ISH pattern suggested that increased amounts of PEPCK were synthesized in recruited cells which contained little enzyme under physiological conditions. mRNA levels for PEPCK, PDG, and GDH peaked at 10 h before returning to control levels. Despite the decrease in mRNAs, a sustained increase in proteins was noted.
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PMID:Changes in mRNAs for enzymes of glutamine metabolism in kidney and liver during ammonium chloride acidosis. 791 34

We have evaluated the effect of alpha-ketoisocaproic acid (KIC), the ketoacid of leucine, on the production of glutamine by cultured astrocytes. We used 15NH4Cl as a metabolic tracer to measure the production of both [5-15N]glutamine, reflecting amidation of glutamate via glutamine synthetase, and [2-15N]glutamine, representing the reductive amination of 2-oxoglutarate via glutamate dehydrogenase and subsequent conversion of [15N]glutamate to [2-15N]glutamine. Addition of KIC (1 mM) to the medium diminished the production of [5-15N]glutamine and stimulated the formation of [2-15N]glutamine with the overall result being a significant inhibition of net glutamine synthesis. An external KIC concentration as low as 0.06 mM inhibited synthesis of [5-15N]glutamine and a level as low as 0.13 mM enhanced labeling (atom% excess) of [2-15N]glutamine. Higher concentrations of KIC in the medium had correspondingly larger effects. The presence of KIC in the medium did not affect flux through glutaminase, which was measured using [2-15N]glutamine as a tracer. Nor did KIC inhibit the activity of glutamine synthetase that was purified from sheep brain. Addition of KIC to the medium caused no increased release of lactate dehydrogenase from the astrocytes, suggesting that the ketoacid was not toxic to the cells. KIC treatment was associated with an approximately twofold increase in the formation of 14CO2 from [U-14C]glutamate, indicating that transamination of glutamate with KIC increases intraastrocytic alpha-ketoglutarate, which is oxidized in the tricarboxylic acid cycle. KIC inhibited glutamine synthesis more than any other ketoacid tested, with the exception of hydroxypyruvate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of astrocyte glutamine production by alpha-ketoisocaproic acid. 793 4

Chronic renal failure (CRF) is associated with a sundry of abnormalities in pancreatic islets including a rise in their cytosolic calcium, reduced ATP content, and impaired glucose-induced insulin secretion. The latter is also stimulated by amino acids (such as leucine), and the cellular processes involved in leucine-induced insulin secretion are different from those responsible for glucose-induced insulin release. The present study examined whether leucine-induced insulin secretion is also impaired in CRF and investigated the cellular derangements for such a potential abnormality. The results showed that leucine-induced insulin secretion is markedly reduced by islets from CRF animals, and this defect was prevented by parathyroidectomy (PTX) of the CRF animals or by their treatment with verapamil, an agent that blocks the action of parathyroid hormone (PTH) on the pancreatic islets. Both leucine uptake and alpha-ketoisocaproic acid-induced insulin secretion by islets from CRF rats are normal; however, both the activation of glutamate dehydrogenase (GLDH) by leucine or by 2-aminobicyclo-[2-2-1]-haptene and the utilization of alpha-ketoglutarate are impaired, and the maximal reaction rate (Vmax) of glutaminase is reduced. These derangements are corrected by PTX of CRF rats or by their treatment with verapamil. The data demonstrate that 1) CRF is associated with impaired leucine-induced insulin secretion, 2) this defect is due to the state of secondary hyperparathyroidism of CRF, and 3) the cellular derangements responsible for this defect involve abnormalities in the metabolism of leucine and derangements in the leucine-GLDH-alpha-ketoglutarate-glutaminase pathway of the islets.
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PMID:Abnormal leucine-induced insulin secretion in chronic renal failure. 797 90


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