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)

Amino acids of the glutamate family, viz. glutamic acid, aspartic acid, glutamine, gamma-amino-butyric acid (GABA) and alanine, along with the activities of glutamic acid dehydrogenase (GDH), aspartic acid aminotransferase (AST), alanine aminotransferase (ALT), glutamine synthetase (GS), glutaminase, glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) were estimated in cerebral cortex, cerebellum and brain stem of rats treated with a single dose of lithium or with seven daily doses of lithium (3 m-equiv./kg body wt). The levels of GABA were found to increase in cerebral cortex and brain stem following the administration of a single dose and also were found to be increased in cerebral cortex and cerebellum after treatment for 7 days. The content of glutamic acid was increased in all three brain regions after treatment for 7 days. Glutamine was increased in both cerebral cortex and brain stem after treatment for 7 days, whereas aspartic acid was increased in brain stem after both the administration of single dose and treatment for 7 days. A significant increase (P less than 0.05) in the activity of GS was observed in brain stem after 7 days of treatment. Similarly, a significant increase (P less than 0.01) in the activity of AST was observed in all three regions of the brain following the treatment for 7 days. The above results are discussed in relation to the known effects of lithium on brain cation metabolism and a suggestion is made that an imbalance in the functional activities of glutamic acid and GABA as a result of quantitative changes in these amino acids, brought about by lithium, may play a role in the therapeutic efficacy of lithium in bipolar disorders.
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PMID:Acute and short-term effects of lithium on glutamate metabolism in rat brain. 286 24

(1) Adult postprandial rats were given a continuous, intravenous infusion of 15N-labelled glutamate, alanine, ammonium chloride and glutamine amide for 6 h. The enrichment in the free hepatic pool was measured for ammonia, glutamine amide, urea, aspartate, glutamate and alanine. (2) Glutamine and glutamate supplied significantly more nitrogen to urea than ammonium chloride or alanine. (3) Glutamate was not a significant source of hepatic ammonia, hence in this situation it is not necessary to impute a major role to glutamate dehydrogenase in hepatic ammoniagenesis for urea synthesis. (4) Glutamine and ammonia, mostly of intestinal origin in the postprandial state, were major precursors of hepatic ammonia. (5) The nitrogen of glutamate and alanine moved to urea primarily through aspartic acid.
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PMID:In vivo metabolism of nitrogen precursors for urea synthesis in the postprandial rat. 290 40

The literature concerning the metabolism of carbon and nitrogen compounds in ectomycorrhizal associations of trees is reviewed. The absorption and translocation of mineral ions by the mycelia require an energy source and a reductant which are both supplied by respiratory catabolism of carbohydrates produced by the host plant. Photosynthates are also required to generate the carbon skeletons for amino acid and carbohydrate syntheses during the growth of the mycelia. Competition for photosynthates occurs between the fungal cells and the various vegetative sinks in the host tree. The nature of carbon compounds involved in these processes, their routes of metabolism, the mechanisms of control and the partitioning of metabolites between the various sites of utilization are only poorly understood. Both ascomycetous and basidiomycetous ectomycorrhizal fungi synthesize and some, if not all, accumulate mannitol, trehalose and triglycerides. The fungal strains employ the Embden--Meyerhof pathway of glucose catabolism and the key enzymes of the pentose phosphate pathway (6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, transaldolase and transketolase). Anaplerotic CO2 fixation, via pyruvate carboxylase and/or phosphoenolpyruvate carboxykinase, provides high pools of amino acids. This process could be important in the recapture and assimilation of respired CO2 in the rhizosphere. The ectomycorrhizas are thought to contain the Embden--Meyerhof pathway, the pentose phosphate pathway and the tricarboxylic acid cycle, which provide the carbon skeletons for the assimilation of ammonia into amino acids. The main route of assimilation of ammonia appears to be through the glutamine synthetase-glutamate synthase cycle in the ectomycorrhizas. Glutamate dehydrogenase plays a minor role in this process. Glutamate dehydrogenase and glutamine synthetase are present in free-living ectomycorrhizal fungi and they participate in the assimilation of ammonia and the synthesis of amino acids through the glutamate dehydrogenase/glutamine synthetase sequence. In both in vitro cultures of fungi and ectomycorrhizas, the assimilated nitrogen accumulates in glutamine. Glutamine, but also ammonia, are thought to be exported from the fungal tissues to the host cells. Studies on the metabolism of ectomycorrhizas and ectomycorrhizal fungi have focused on the metabolic pathways and compounds which accumulate in the symbiotic tissues. Studies on regulation of the overall process, and the control of enzyme activity in particular, are still fragmentary.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carbon and nitrogen metabolism in ectomycorrhizal fungi and ectomycorrhizas. 312 Jul 92

Measurement of the arteriovenous differences for free amino acids across rat kidney reveals that glycine and citrulline are removed and serine and arginine are added to the circulation. In addition, glutamine is taken up in large quantities by kidneys of animals that need to excrete large quantities of acid (e.g., diabetic animals, NH4Cl-fed animals, and animals fed a high protein diet). Glutamine is the major precursor of urinary ammonia and thus renal glutamine metabolism plays a key role in acid-base homeostasis. This process occurs primarily in the cells of the convoluted proximal tubule. Glutamine carbon is converted to glucose in acidotic rats and is totally oxidized in dogs. Regulation of glutamine metabolism occurs at two levels: acute regulation and chronic regulation. Acute regulation is, in part, mediated through a fall in intracellular [H+]. This activates alpha-ketoglutarate dehydrogenase and, ultimately, glutaminase. Chronic regulation involves induction of key enzymes, including, in the rat, glutaminase, glutamate dehydrogenase, and phosphoenolpyruvate carboxykinase. During the acidosis of prolonged starvation, the kidneys' requirement for glutamine must be met from muscle proteolysis and thus becomes a drain on lean body mass. Serine synthesis occurs by two separate pathways: from glycine by the combined actions of the glycine cleavage enzyme and serine hydroxymethyltransferase and from gluconeogenic precursors using the phosphorylated-intermediate pathway. Both pathways are located in the cells of the proximal tubule. Conversion of glycine to serine is ammoniagenic and the activity of the glycine cleavage enzyme is increased in acidosis. The function of serine synthesis by the phosphorylated-intermediate pathway is not apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1986 Borden award lecture. The role of the kidney in amino acid metabolism and nutrition. 332 68

In vitro resting, short-term mitogen stimulated, and proliferating rat thymocytes as well as established human T and B lymphoblastoid cell lines were compared in their capacity to metabolize glucose and glutamine as energy source. Furthermore, the pathways of glutamine metabolism in these cells were studied. Compared with resting thymocytes, glucose metabolism of proliferating thymocytes was 36-fold increased during the incubation; 92% of the amount of glucose utilized was converted into trioses mainly lactate, whereas resting cells metabolized only 38% to trioses. However, the latter oxidized 19% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Rates of glucose uptake and degradation to products by the malignant T lymphoblastoid cell line (Jurkat) were nearly identical with those observed with proliferating rat thymocytes, whereas the benign B lymphoblastoid cell lines (DHg-B-1 and LV-B-1) showed significantly higher rates of glucose metabolism. All three transformed lymphoblastoid cell lines, however, metabolized glucose almost completely to lactate as did the proliferating rat thymocytes. Lymphocytes are able to utilize glutamine with glutamate, aspartate and ammonia being the major end-products. A complete recovery of glutamine carbon in the products was obtained with all cells. Glutamine utilization by incubated proliferating rat thymocytes was 8-fold increased as compared to the resting cells. Again the human T lymphoblastoid cell line showed the same rates of glutamine uptake and conversion into products as did the proliferating rat thymocytes, whereas both B lymphoblastoid cell lines had about 2.5-fold enhanced rates as compared to the T cell line. The results indicate that during lymphocyte proliferation caused by mitogen stimulation as well as by permanent transformation into lymphoblastoid cell lines glucose metabolism is altered not only quantitatively but also qualitatively by changing from partly aerobic to almost complete anaerobic glucose breakdown. Glutamine has been found to be a suitable energy source for lymphocytes. About 75% of the amount of glutamate derived from glutamine entered into the citric acid cycle via the aspartate aminotransferase, and the remaining 25% via the glutamate dehydrogenase reaction. The changes in metabolic rates observed in proliferating as well as in transformed or leukemic lymphocytes appear to be reliable parameters to characterize the state of lymphocyte activation or to evaluate the efficacy of lymphokines.
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PMID:Metabolic alterations associated with proliferation of mitogen-activated lymphocytes and of lymphoblastoid cell lines: evaluation of glucose and glutamine metabolism. 349 37

Mutants of the yeast Saccharomyces cerevisiae have been isolated which fail to derepress glutamine synthetase upon glutamine limitation. The mutations define a single nuclear gene, GLN3, which is located on chromosome 5 near HOM3 and HIS1 and is unlinked to the structural gene for glutamine synthetase, GLN1. The three gln3 mutations are recessive, and one is amber suppressible, indicating that the GLN3 product is a positive regulator of glutamine synthetase expression. Four polypeptides, in addition to the glutamine synthetase subunit are synthesized at elevated rates when GLN3+ cultures are shifted from glutamine to glutamate media as determined by pulse-labeling and one- and two-dimensional gel electrophoresis. The response of all four proteins is blocked by gln3 mutations. In addition, the elevated NAD-dependent glutamate dehydrogenase activity normally found in glutamate-grown cells is not found in gln3 mutants. Glutamine limitation of gln1 structural mutants has the opposite effect, causing elevated levels of NAD-dependent glutamate dehydrogenase even in the presence of ammonia. We suggest that there is a regulatory circuit that responds to glutamine availability through the GLN3 product.
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PMID:Regulation of glutamine-repressible gene products by the GLN3 function in Saccharomyces cerevisiae. 615 12

Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.
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PMID:The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies. 681 56

beta-Hydroxybutyrate (but not acetoacetate) caused marked inhibition of ammonia production and glutamine extraction in isolated perfused kidneys from normal rats. Glutamine synthesis was not affected by beta-hydroxybutyrate (BHB). Measurement of metabolite levels in freeze-clamped kidneys showed that BHB increased glutamine concentration, decreased ammonia concentration, and reduced the mitochondrial NAD+/NADH ratio (calculated) in perfused kidneys. BHB inhibited flux through the glutamate dehydrogenase pathway, probably as a result of reduction in the NAD+/NADH ratio, in isolated renal mitochondria. In isolated perfused kidneys from acidotic rats, ammonia production and mitochondrial NAD+/NADH were both elevated and BHB did not inhibit renal ammoniagenesis. Although ammonia production in the acidotic kidneys was not directly related to the mitochondrial NAD+/NADH ratio, the elevation of this ratio may have permitted a normal rate of oxidation of glutamine end products--which is essential for maintaining the elevated ammoniagenesis--to take place in the presence of BHB.
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PMID:Ketone body effects on glutamine metabolism in isolated kidneys and mitochondria. 711 17

The effect of the tricarboxylic acid (TCA) cycle precursor, pyruvate, on glutamine metabolism by isolated renal cortical mitochondria was assessed by quantitating its key nitrogen and carbon metabolites. When mitochondria from normal rats were incubated at pH 7.4, pyruvate (2 mM) inhibited ammonia production by almost completely erradicating glutamate deamination and by diminishing glutamine deamidation but to a lesser extent. Alpha KG, citrate, and malate accumulation in the incubation medium were increased dramatically reflecting the increased flux of pyruvate through the TCA cycle; the intramitochondrial concentrations of both Alpha KG and glutamate were increased. Thus, pyruvate primarily inhibits flux through glutamate dehydrogenase as a result either of an increase in Alpha KG concentration and/or a decrease in the redox (NAD/NADH) potential secondary to enhanced flux through the TCA cycle. Glutamine deamidation is secondarily inhibited, presumably due to the increased intramitochondrial concentration of glutamate. Citrate (2 mM) produced changes comparable to those observed with pyruvate. Mitochondria from normal rats incubated at pH 7.0 as well as mitochondria from rats with chronic metabolic acidosis responded to pyruvate in a fashion qualitatively similar to normal mitochondria incubated at pH 7.4. Glutamate deamination was inhibited significantly, but a high rate persisted with chronic acidosis despite the presence of pyruvate. Nevertheless, when glutamine metabolism was contrasted with normal mitochondria incubated at pH 7.4, the response to in vitro incubation in an acid pH as well as to chronic metabolic acidosis was similar quantitatively regardless of whether glutamine alone or in combination with pyruvate was present in the incubation medium.
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PMID:Influence of pyruvate on ammonia metabolism by renal cortical mitochondria. 717 30

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


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