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

---

Query: EC:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study deals with the effect of atrazine on nitrogen metabolism in the liver and brain of fish. Significant changes were seen in the levels of proteins, free amino acids, ammonia, urea, glutamine and the activity levels of proteases, glucogenic aminotransferases, branched-chain aminotransferases, glutamate dehydrogenase, glutaminase, arginase, AMP deaminase and adenosine deaminase in both the tissues of fish exposed to sublethal concentration of atrazine. The study reflects a shift in nitrogen concentration of atrazine. The study reflects a shift in nitrogen metabolism in the tissues of fish for efficient mobilization of end products of protein catabolism as a consequence of atrazine.
...
PMID:Modulations in nitrogen metabolism in the hepatic and neuronal tissues of fish, Tilapia mossambica exposed to atrazine. 185 31

It has been found that there exists a correlation in the dynamics of changes in the amount of glutamate, alpha-ketoglutarate, glutamine, ammonia and activity level or alpha-ketoglutarate dehydrogenase, NADP-glutamate dehydrogenase, glutamine synthetase and glutaminase in the brain of young carp in the process of winter starvation. It has been stated that under condition of energy deficiency and meaningful amount of ammonia in the organism of hibernating fish, its binding parallel with the known glutamine synthetase mechanism may proceed in the course of the NADP-glutamate dehydrogenase reaction which balance is shifted towards the glutamate synthesis. This reaction is supposed to provide the outflow of alpha-ketoglutarate from the citric cycle, which intensifies energy deficiency of the organism.
...
PMID:[Features of the interconversion of alpha-ketoglutarate--glutamate in brain mitochondria of exothermic animals during hibernation]. 198 77

We utilized gas chromatography-mass spectrometry to study the transfer of 15N from [2-15N]glutamine, [15N]leucine, [15N]alanine, or 15NH4Cl to [15N]glutamate and [15N]aspartate in cultured cerebrocortical GABA-ergic neurons from the mouse. Initial rates of 15N appearance (atom % excess) were somewhat higher with 2mM [2-15N]glutamine as a precursor than with 1mM [15N]leucine or 1mM [15N]alanine, but initial net formation (nmol [15N]glutamate/mg protein.min-1) was roughly comparable with all precursors. At steady-state 15N labeling was about two times greater with 2mM [2-15N]glutamine as precursor. The subsequent transfer of 15N from glutamate to aspartate was extremely rapid, the labelling pattern of these two amino acid pools being virtually indistinguishable. We observed little reductive amination of 2-oxo-glutarate to yield [15N]glutamate in the presence of 0.3mM 15NH4Cl. Reductive amination through glutamate dehydrogenase was much more prominent at a concentration of 3.0mM 15NH4Cl. Glutamate formation via reductive amination was unaffected by inclusion of 1mM 2-oxo-glutarate in the incubation medium. These results indicate that glutamate synthesis in cultured GABA-ergic neurons is derived not only from the glutaminase reaction, but also from transamination reactions in which both leucine and alanine are efficient N donors. Reductive amination of 2-oxo-glutarate in the glutamate dehydrogenase pathway plays a relatively minor role at lower concentrations of extracellular ammonia but becomes quite active at 3mM ammonia.
...
PMID:Precursors of glutamic acid nitrogen in primary neuronal cultures: studies with 15N. 209 13

We studied the effects of sodium valproate, a widely used antiepileptic drug and a hyperammonemic agent, on L-[1-14C]glutamine and L-[1-14C]glutamate metabolism in isolated human kidney-cortex tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, 14CO2, pyruvate, lactate and alanine, but it inhibited glucose synthesis; the increase in ammonia formation was explained by a stimulation by valproate mainly of flux through glutaminase (EC 3.5.1.2) and to a much lesser extent of flux through glutamate dehydrogenase (EC 1.4.1.3). By contrast, valproate did not stimulate glutamate removal or ammonia formation, suggesting that the increase in flux through glutamate dehydrogenase observed with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was less from glutamate than from glutamine. Inhibition by aminooxyacetate of accumulation of alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. It is concluded from these data, which are the first concerning the in vitro metabolism of glutamine and glutamate in human kidney-cortex tubules, that the stimulatory effect of valproate is primarily exerted at the level of glutaminase in human renal cortex.
...
PMID:Effect of the antiepileptic drug sodium valproate on glutamine and glutamate metabolism in isolated human kidney tubules. 210 74

In a previous study we demonstrated thirteen amino acids to be essential and two to be partially essential for lymphocyte proliferation. Arginine is one of the essential amino acids, and the highly purified arginase strongly inhibited lymphocyte proliferation. The modulation of lymphocyte growth by various amino acid-degrading enzymes was studied. Peripheral lymphocytes were cultured in RPMI 1640 with or without amino acid-degrading enzyme for 72 h. A total of 17 commercial L-amino acid-degrading enzymes were studied. At 10 micrograms/ml, both lysine decarboxylase and asparaginase completely inhibited lymphocyte proliferation, arginase resulted in 78% inhibition and tyrosinase 57% inhibition. Other enzymes inhibited less than 20% lymphocyte proliferation; they included alanine dehydrogenase, arginine decarboxylase, aspartase, glutamic decarboxylase, glutamic dehydrogenase, glutaminase, histidase, histidine decarboxylase, leucine dehydrogenase, phenylalanine decarboxylase, phenylalanine hydroxylase, tryptophanase, and tyrosine decarboxylase. All four enzymes that strongly inhibited lymphocyte proliferation degraded amino acids that are essential for lymphocyte growth.
...
PMID:Modulation of lymphocyte proliferation by enzymes that degrade amino acids. 212 55

Patients with McArdle's disease (myophosphorylase deficiency) cannot use muscle glycogen as an energy source during exercise. They therefore are an ideal model to learn about the metabolic adaptations which develop during endurance exercise leading to glycogen depletion. This review summarizes the current knowledge of ammonia and amino acid metabolism in these patients and also adds several new data. During incremental exercise tests in patients with McArdle's disease, forearm venous plasma ammonia concentration rises to a value between 200 and 500 microM. Femoral arteriovenous difference studies show that muscle produces the ammonia. The leg release of both ammonia and glutamine (in mumol/min) has been estimated to be five- to tenfold larger in one of these patients than in healthy individuals exercising at comparable relative work load. Patients with McArdle's disease have a larger uptake of branched-chain amino acids (BCAA) by exercising leg muscles and show a more rapid activation of the muscle branched-chain 2-oxo acid dehydrogenase complex, a key enzyme in the degradation of the BCAA. In general, supplements of BCAA taken before the exercise test lead to a deterioration of exercise performance and a higher increase in heart rate and plasma ammonia during exercise, whereas supplements of branched-chain 2-oxo acids improve exercise performance and lead to a smaller increase in heart rate and plasma ammonia. At constant power output, patients with McArdle's disease show a rapid increase in heart rate and exertion perceived in the exercising muscles, which peak within 10 min after the start of exercise and then fall again ("second wind"). Peak heart rate and peak exertion coincide with a peak in plasma ammonia. Ammonia production during exercise in these patients is estimated to exceed the reported breakdown of ATP to IMP and therefore most likely originates from the metabolism of amino acids. Deamination of amino acids via the reactions of the purine nucleotide cycle and glutamate dehydrogenase are possible pathways. Deamination of glutamine, released by muscle, by glutaminase present in the endothelial cells of the vascular system may also contribute to the ammonia production. The observations made in these patients have led to the hypothesis that excessive acceleration of the metabolism of BCAA drains 2-oxoglutarate in the primary aminotransferase reaction and thus reduces flux in the citric acid cycle and impedes aerobic oxidation of glucose and fatty acids. This draining effect is normally counteracted by the anaplerotic conversion of muscle glycogen to citric acid cycle intermediates, a reaction which is severely hampered in these patients due to the glycogen breakdown defect.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Metabolism of branched-chain amino acids and ammonia during exercise: clues from McArdle's disease. 219 89

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).
...
PMID:Ammonium metabolism: emphasis on energy considerations. 228 91

The metabolic fate of 15N-labeled glutamine and glutamate in cultured human renal cortical epithelial cells was investigated. The main goal was to elucidate the major pathways of ammoniagenesis depending on varying H+ concentration. Incubations at pH 7.4 or 6.8 were conducted with either 1 mM [5-15N]glutamine, [2-15N]glutamine, [15N]glutamate, or L-[2-15N]-gamma-glutamylmethylamide. The results demonstrate that acute acidosis had little effect on total ammonia generation from glutamine. However, 15NH3 formation from [5-15N]glutamine was significantly higher at pH 7.4 compared with pH 6.8. Conversely, at pH 6.8, 15NH3 production from either [2-15N]-glutamine or [15N]glutamate was twofold higher than at pH 7.4. Thus the observations indicate that acute acidosis had little effect on net ammonia production from glutamine due to decreased flux through glutaminase and concomitant increased flux through glutamate dehydrogenase. When L-[2-15N]-gamma-glutamylmethylamide was utilized as the sole substrate, significantly higher amounts of 15NH3 and 15N-labeled amino acids were formed at pH 6.8 compared with pH 7.4. Addition of either 1 mM pyruvate or alpha-ketoglutarate significantly decreased 15NH3 and increased 15N-amino acid formation from either [2-15N]glutamine or [2-15N]-gamma-glutamylmethylamide. The metabolism of either substrate via transamination reaction was significantly stimulated at acidic pH, presumably due to a depleted pool of alpha-ketoglutarate during the course of the incubations. The data indicate that in addition to glutaminase I and glutamate dehydrogenase, the glutamine aminotransferase (glutaminase II) pathway exists in cultured human renal cells. The data suggest that glutamate dehydrogenase flux and/or the alpha-ketoglutarate dehydrogenase reaction may have an important regulatory role in ammoniagenesis from glutamine and/or glutamate in human kidney during acute acidosis.
...
PMID:Ammoniagenesis by cultured human renal cortical epithelial cells: study with 15N. 280 65

The effects of sodium valproate, a widely used antiepileptic drug and an hyperammonemic agent, on glutamine and glutamate metabolism were studied in isolated dog kidney tubules. Valproate markedly stimulated glutamine removal as well as the formation of ammonia, aspartate, pyruvate, lactate, alanine and glucose; the increase in ammonia formation was explained by a stimulation by valproate of flux not only through glutaminase (EC 3.5.1.2) but also through glutamate dehydrogenase (EC 1.4.1.3). By contrast, valproate did not stimulate glutamate removal or ammonia, aspartate and glucose formation from glutamate; this suggests that the increase in flux through glutamate dehydrogenase with glutamine as substrate was secondary to the increase in flux through glutaminase. Accumulation of pyruvate, alanine and lactate in the presence of valproate was much less from glutamate than from glutamine. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by valproate did not prevent the acceleration of glutamine utilization and the subsequent stimulation of ammonia formation. These data are consistent with a stimulatory effect of valproate primarily exerted at the level of glutaminase in dog kidney tubules. However, the fact that assayed activity of glutaminase remained unchanged in the presence of valproate suggests that this compound accelerates flux through the latter enzyme by an indirect mechanism probably related to the renal metabolism of this compound.
...
PMID:Stimulation of glutamine metabolism by the antiepileptic drug, sodium valproate, in isolated dog kidney tubules. 257 76

The activity of glutamate related enzymes and the concentration of glutamine, glutamate and gamma-amino n-butyric acid (GABA) were investigated in the cerebral cortex of rats, in different stages of insulin-induced hypoglycemia. Hypoglycemia was produced by intraperitoneal injection of insulin 0.05-100 units per kg body weight. The minimum required dose to produce irreversible severe hypoglycemia was 0.5 units/kg. In 85% of the cases an insulin induced hypoglycemic convulsion, was achieved 130-150 minutes after injection. Blood glucose levels during insulin induced seizures ranged between 8-15 mg%. In the range of 0.5-100 u insulin/kg the degree of hypoglycemia and the onset of convulsions were identical. The concentration of glutamine was significantly reduced during convulsive and postconvulsive stages. Glutamate and GABA concentrations were reduced significantly in all stages of insulin-induced hypoglycemia. The decrease in glutamine concentration was concurrent with an increase in the activity of its degradative enzyme, glutaminase. This was apparent at the preconvulsive, convulsive and postconvulsive stages. The activity of other enzymes related to energy production such as glutamate dehydrogenase (GDH), glutamate transaminase (GPT) and aspartate aminotransferase (AAT) were also increased. The activity of glutamine synthase (GS) was unaffected by hypoglycemia. Insulin induced changes in glutamine, glutamate and their related enzymes could not be attributed to convulsion since a similar pattern of changes was observed in the preconvulsive and postconvulsive stages, and no changes were detected following picrotoxin-induced seizures.
...
PMID:Changes in the activity of glutamate related enzymes in cerebral cortex, during insulin-induced seizures. 257 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---