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)

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Alanine release from skeletal muscle was increased by fasting (65%), cortisone (145%), thyroxine (200%), and diabetes (185%). Glutamine release was decreased by cortisone (37%) and diabetes (23%) but not significantly affected by fasting or thyroxine. Tissue levels of alanine were unchanged but tissue glutamine levels were markedly reduced (30 to 60%) in all treatment groups. Insulin added in vitro did not affect amino acid release even with preparations obtained from diabetic animals. Inhibition of glycolysis with 0.2 mM iodoacetate had no effect on the rate of alanine and glutamine formation in any treatment group. Pyruvate generation was increased by all treatments even in the presence of the inhibitor. Total skeletal muscle alanine, aspartate, and branched chain aminotransferase, glutamate dehydrogenase, and malic enzyme activities were not significantly altered in any treatment groups. The addition of 10 mM aspartate, cysteine, branched chain amino acids, and serine significantly increased alanine formation, whereas the maximal rate of glutamine formation in the presence of stimulating amino acids was reduced in each treatment groups--the most marked effects were noted with cortisone and diabetic preparations. Although accelerated muscle proteolysis is an important factor regulating alanine formation in skeletal muscle, the redirection of carbon flow from glutamine toward alanine formation observed in fasting, cortisone, thyroxine-treated, and diabetic rats, indicates that factors other than proteolysis also participate in the control of amino acid release from muscle.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. III. Dietary and hormonal regulation. 12 73

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.
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PMID:Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat. 159 Jun 69

The LLC-PK1 renal epithelial cell line has been used as a model system to study renal ammoniagenesis and its regulation by metabolic acidosis in vitro. Experiments were performed on confluent LLC-PK1 epithelia grown for 10-14 days in conventional monolayer technique. After the medium pH was changed from 7.6 to 7.0 for 24-72 h by lowering the bicarbonate concentration in culture medium, LLC-PK1 cells responded with an adaptive increase in glutamine consumption and ammonia production. The rates of glutamine uptake and ammonia generation displayed a ratio of 1:1, i.e., 1 mol ammonia was produced per mole of glutamine consumed. Glutamine consumption and ammonia formation were paralleled by an equimolar production of L-alanine, indicating that transamination appears to be the main ammoniagenic pathway in LLC-PK1 cells. Analysis of the key enzymes of renal ammoniagenesis, phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH), revealed no changes in enzyme activities up to 72 h of adaptation. Alanine aminotransferase (ALT) activity in LLC-PK1 cells also remained unchanged during the adaptation period. Because transamination seems to play a crucial role in channeling the metabolic flux in LLC-PK1 ammoniagenesis, experiments were performed in which transamination was inhibited by (aminooxy)acetate (AOA). After incubation of control and pH 7.0-adapted LLC-PK1 cultures for 24-72 h in 0.2 mM AOA, no alanine production was found, but 2 mol of ammonia were formed per mole of glutamine consumed, again, without adaptive changes in PDG and GDH activities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ammoniagenesis in LLC-PK1 cultures: role of transamination. 163 83

Pregnant rats of 19th and 21st days were given an acute nitrogen overload produced by an infusion of either 0.2 M ammonium acetate or 0.2 M glutamine. Metabolic adaptations to nitrogen excess were studied measuring--in fetomaternal unit--non-protein nitrogen content and the activities of enzymes related with ammonia metabolism. Maternal and fetal plasma urea levels were increased by ammonium acetate treatment. Glutamine overload increased more the amino acid content in the mothers than in conceptus. As response to ammonium acetate treatment, glutamate dehydrogenase activity in liver was more sensitive in pregnant than in nonpregnant rats, suggesting more nitrogen incorporation into amino acids in pregnancy. Regarding glutamine synthetase activity, both treatments had an opposite effect except in kidney. The adenylate deaminase activity of pregnant rats was inhibited similarly to nonpregnant rats by nitrogen overloads, but stronger after glutamine infusion. Placenta and fetal metabolism were adjusted, as the dams, to lack of ammonia production by nitrogen overloads and to glutamine synthesis by ammonium acetate infusion.
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PMID:Metabolic adaptations to nitrogen excess in late gestation in rat. 177 94

Much evidence has accumulated to support the idea that leucine can stimulate insulin release by allosterically activating glutamate dehydrogenase thus enhancing glutamate metabolism. It is less clear how the metabolism of leucine itself contributes to the signal for insulin release. We recently found that culturing pancreatic islets for 1 day at low glucose (1 mM) suppressed glucose-induced insulin release, but preserved leucine-induced insulin release. When islets were cultured at high glucose (20 mM), glucose-induced insulin release was preserved, but leucine-induced insulin release was suppressed (MacDonald, M. J., Fahien, L. A., McKenzie, D. I., and Moran, S. M. (1990) Am. J. Physiol., 259, E548-E554). The suppression of leucine-induced insulin release can be explained by glucose's suppression of the synthesis of the enzyme that catalyzes the first committed step of leucine metabolism, branched chain ketoacid dehydrogenase complex (BCKDH). High glucose suppressed the enzyme activity of the E1 component of the BCKDH complex, as well as the total activity of the BCKDH complex, to usually negligible levels in islets and decreased by an average of 90% the mRNA which encodes E1 alpha, the catalytic subunit of the E1 component of BCKDH, in islets and rat insulinoma cells. Time course studies showed that about 24 h in culture was required to maximally induce or suppress the expression of BCKDH E1 alpha. Culture at high glutamine with or without leucine mimicked to a lesser and more variable degree the effects of high glucose on leucine-induced insulin release and BCKDH E1 alpha mRNA. Leucine-plus-glutamine-induced insulin release was present after culture of islets with glucose and with or without any other secretagogue. Also, glutamate dehydrogenase transcripts and enzyme activity were not significantly altered by varying the concentration of glucose in the culture medium. Thus, leucine's insulinotropism via activation of glutamate dehydrogenase is constitutive. Preproinsulin mRNA levels were markedly increased at high glucose and glyceraldehyde phosphate dehydrogenase transcripts were either unaffected or slightly increased by glucose. Glutamine did not significantly effect the expression of genes other than BCKDH E1 alpha, and leucine had little or no effect on the expression of any of the four genes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucose regulates leucine-induced insulin release and the expression of the branched chain ketoacid dehydrogenase E1 alpha subunit gene in pancreatic islets. 198 51

1. Glutamine was found to be the main carbon and nitrogen product of the metabolism of aspartate in isolated guinea-pig kidney-cortex tubules. Glutamate, ammonia and alanine were only minor products. 2. Carbon-balance calculations and the release of 14CO2 from [U-14C]aspartate indicate that oxidation of the aspartate carbon skeleton occurred. 3. A pathway involving aspartate aminotransferase, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate dehydrogenase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of aspartate into glutamine. 4. Evidence for this pathway was obtained by: (i) inhibiting aspartate removal by amino-oxyacetate, an inhibitor of transaminases, (ii) the use of methionine sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from aspartate, (iii) the use of quinolinate, an inhibitor of phosphoenolpyruvate carboxykinase, which inhibited glutamine synthesis from aspartate, (iv) the use of alpha-cyano-4-hydroxycinnamate, an inhibitor of the mitochondrial transport of pyruvate, which caused an accumulation of pyruvate from aspartate, and (v) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from aspartate.
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PMID:Glutamine synthesis from aspartate in guinea-pig renal cortex. 236 82

The infusion of ether anesthaetized rats with 0.2 M (1 mmols in total) ammonium acetate or glutamine were compared with the infusion of 0.2 M NaCl. The levels of circulating glucose, amino acids, lactate, urea and ammonium were measured as well as liver glycogen and tissue amino acids and the liver and muscle activities of carbamoyl phosphate synthetases I and II, glutamate dehydrogenase, glutamine synthetase and adenylate deaminase. Neither treatment altered the glucose and glycogen homeostasis. The infusion of ammonium did not result in increases in circulating ammonium, but resulted in increased circulating urea after a short delay; the infusion of glutamine resulted also in urea production but much later on. Glutamine infusion also resulted in increased tissue free amino-acid levels. There was little alteration in enzyme activities, except for decreased glutamine synthetase and adenylate deaminase activity in muscle of glutamine-infused rats and higher tissue carbamoyl phosphate synthetase II. The results agree with a fast removal of infused ammonium, and maintenance of glutamine, with their channeling towards urea production at a rate comparable with that of infusion, that did not alter significantly the homeostasis of the experimental animals.
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PMID:Glutamine and ammonium handling by anaesthetized rats. 247 81

Streptococcus bovis JB1 cells energized with glucose transported glutamine at a rate of 7 nmol/mg of protein per min at a pH of 5.0 to 7.5; sodium had little effect on the transport rate. Because valinomycin-treated cells loaded with K and diluted into Na (pH 6.5) to create an artificial delta psi took up little glutamine, it appeared that transport was driven by phosphate-bond energy rather than proton motive force. The kinetics of glutamine transport by glucose-energized cells were biphasic, and it appeared that facilitated diffusion was also involved, particularly at high glutamine concentrations. Glucose-depleted cultures took up glutamine and produced ammonia, but the rate of transport per unit of glutamine (V/S) by nonenergized cells was at least 1,000-fold less than the V/S by glucose-energized cells. Glutamine was converted to pyroglutamate and ammonia by a pathway that did not involve a glutaminase reaction or glutamate production. No ammonia production from pyroglutamate was detected. S. bovis was unable to take up glutamate, but intracellular glutamate concentrations were as high as 7 mM. Glutamate was produced from ammonia via a glutamate dehydrogenase reaction. Cells contained high concentrations of 2-oxoglutarate and NADPH that inhibited glutamate deamination and favored glutamate formation. Since the carbon skeleton of glutamine was lost as pyroglutamate, glutamate formation occurred at the expense of glucose. Arginine deamination is often used as a taxonomic tool in classifying streptococci, and it had generally been assumed that other amino acids could not be fermented. To our knowledge, this is the first report of glutamine conversion to pyroglutamate and ammonia in streptococci.
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PMID:Transport of glutamine by Streptococcus bovis and conversion of glutamine to pyroglutamic acid and ammonia. 272 40

Rats were fed a standard diet or the standard diet supplemented with ammonium acetate (20% w/w) for up to 100 days. The effect of the ingestion of the high-ammonium diet on some aspects of nitrogen metabolism in rats was studied. Ammonia levels in blood increased approximately 3-fold; in brain, liver and muscle the increases were 36, 34 and 50%, respectively. Urea levels in blood and urea excretion increased approximately 2-fold. There was no increase of carbamyl phosphate synthase. Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected. Glutamine content in brain was twice that of controls. This new animal model to study hyperammonemia offers several advantages over others: it is simpler, is bloodless, requires no animal manipulation and permits long-term studies.
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PMID:A simple animal model of hyperammonemia. 275 49

Energy metabolism in proliferating cultured rat thymocytes was compared with that of freshly prepared non-proliferating resting cells. Cultured rat thymocytes enter a proliferative cycle after stimulation by concanavalin A and Lymphocult T (interleukin-2), with maximal rates of DNA synthesis at 60 h. Compared with incubated resting thymocytes, glucose metabolism by incubated proliferating thymocytes was 53-fold increased; 90% of the amount of glucose utilized was converted into lactate, whereas resting cells metabolized only 56% to lactate. However, the latter oxidized 27% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and aldolase in proliferating thymocytes were increased 12-, 17-, 30- and 24-fold respectively, whereas the rate of pyruvate oxidation was enhanced only 3-fold. The relatively low capacity of pyruvate degradation in proliferating thymocytes might be the reason for almost complete conversion of glucose into lactate by these cells. Glutamine utilization by rat thymocytes was 8-fold increased during proliferation. The major end products of glutamine metabolism are glutamate, aspartate, CO2 and ammonia. A complete recovery of glutamine carbon and nitrogen in the products was obtained. The amount of glutamate formed by phosphate-dependent glutaminase which entered the citric acid cycle was enhanced 5-fold in the proliferating cells: 76% was converted into 2-oxoglutarate by aspartate aminotransferase, present in high activity, and the remaining 24% by glutamate dehydrogenase. With resting cells the same percentages were obtained (75 and 25). Maximal activities of glutaminase, glutamate dehydrogenase and aspartate aminotransferase were increased 3-, 12- and 6-fold respectively in proliferating cells; 32% of the glutamate metabolized in the citric acid cycle was recovered in CO2 and 61% in aspartate. In resting cells this proportion was 41% and 59% and in mitogen-stimulated cells 39% and 65% respectively. Addition of glucose (4 mM) or malate (2 mM) strongly decreased the rates of glutamine utilization and glutamate conversion into 2-oxoglutarate by proliferating thymocytes and also affected the pathways of further glutamate metabolism. Addition of 2 mM-pyruvate did not alter the rate of glutamine utilization by proliferating thymocytes, but decreased the rate of metabolism beyond the stage of glutamate significantly. Formation of acetyl-CoA in the presence of pyruvate might explain the relatively enhanced oxidation of glutamate to CO2 (56%) by proliferating thymocytes.
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PMID:Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism. 286 9


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