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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Changes in the activity of glutamate related enzymes in cerebral cortex, during insulin-induced seizures. 257 18

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

In vivo studies were performed in the dog to verify if sodium lactate had an important effect on the metabolism of glutamine by the kidney. The animals were infused with 0.6 M sodium lactate to induce acute metabolic alkalosis with plasma bicarbonate of 29.7 mM. During these experiments, it was demonstrated that the renal uptake of glutamine increased by 46%, while the renal production of ammonia was unchanged. The renal production of alanine rose from 6.0 to 16.8 mumol/min. Plasma concentration of lactate increased from 1.3 to 19.2 mM, while that of pyruvate increased from 0.075 to 0.454 mM. In the renal tissue, alpha-ketoglutarate, malate, oxaloacetate, lactate, pyruvate, citrate, and alanine increased significantly. Similar changes were found in the liver and skeletal muscle. The observed changes are best described by transamination of pyruvate and glutamate under the influence of alanine aminotransferase (GPT). It can be calculated that this reaction was responsible for 76% of the production of ammonia from glutamine, the latter being necessary to provide glutamate for the synthesis of alanine. Dogs infused with 0.3 M sodium bicarbonate instead of sodium lactate with the same degree of acute metabolic alkalosis, showed a depression of 40% in the renal uptake of glutamine with a 38% decrease in renal ammoniagenesis and a 20% fall in the production of alanine. The present studies demonstrate that the production of ammonia from glutamine is not necessarily related to changes in acid-base balance, but may be associated with biochemical alterations related to the synthesis of alanine by the kidney.
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PMID:The metabolic response of the kidney to acute sodium lactate alkalosis. 286 25

Using analytical subcellular fractionation techniques, 12% of the total L-alanine aminotransferase activity and 26% of the total L-aspartate aminotransferase activity was localized in enterocyte mitochondria. Alanine and aspartate were products from the oxidation of glutamine and glutamate by enterocyte mitochondria. At low concentrations, malate stimulated aspartate synthesis but was inhibitory at higher concentrations. The malate inhibition of aspartate synthesis, which increased in the presence of pyruvate, was accompanied by an increase in alanine synthesis. With glutamine as substrate in the presence of pyruvate and malate, alanine synthesis was increased by 127% on addition of purified L-alanine aminotransferase, in spite of large amounts of glutamate generated. It was concluded that when pyruvate is available the important route for glutamine or glutamate oxidation by transamination was via L-alanine:2-oxoglutarate aminotransferase and not via L-aspartate:2-oxoglutarate aminotransferase. Results suggested that mitochondria may account for 50% of alanine production from glutamine in the enterocyte despite the relatively low activity of L-alanine aminotransferase therein.
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PMID:Transamination pathways influencing L-glutamine and L-glutamate oxidation by rat enterocyte mitochondria and the subcellular localization of L-alanine aminotransferase and L-aspartate aminotransferase. 286 79

In experiments on 6 sheep the authors found the following enzyme activities in bacteria in the rumen fluid, bacteria adhering to the epithelium of the rumen wall and bacteria adhering to food particles in the rumen (given in nkat X g-1 bacterial dry weight): GDH (NADH): 725 +/- 165, 558 +/- 127, 661 +/- 153; GDH (NADPH): 558 +/- 338, 255 +/- 88, 565 +/- 139; GOAT (NADH): 46 +/- 23, 67 +/- 31, 66 +/- 14; GOGAT/NADPH: 58 +/- 27, 56 +/- 15, 65 +/- 29; GS: 153 +/- 65, 69 +/- 35, 71 +/- 32; ALT: 71 +/- 25, 43 +/- 20, 52 +/- 11; AST: 52 +/- 12, 33 +/- 16, 28 +/- 15. The results show that, except for GDH (NADPH), there were no significant differences between the given enzyme activities in the rumen fluid and in bacteria adhering to the rumen wall and to food. Adherent rumen bacteria have the same potential possibilities as the rumen fluid bacteria for the utilization of ammonia, particularly for the synthesis of glutamic acid, glutamine, alanine and aspartic acid, with the above enzymes as catalysts. By means of the GS/GOGAT system, adherent rumen bacteria can probably synthesize glutamic acid in the presence of a limited NH3 concentration in the rumen.
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PMID:Ammonia-utilizing enzymes of adherent bacteria in the sheep's rumen. 286 70

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

The activity of branched-chain amino acid aminotransferase (EC 2.6.1.42) is reported for four or five different segments of the rat and rabbit nephron as well as for patches from the papilla. In the rat the levels ranged 40-fold, from a high in the thick ascending limb of Henle to a low in the proximal convoluted tubule. The peak activity is far above that reported for most other parts of the body. Maximum activity was located also in the thick ascending limb in the rabbit, but the level was only one-third as high as in the rat. It is postulated that ammonia liberated by this amino transferase, in cooperation with glutamate dehydrogenase, could diffuse readily into the adjacent proximal straight tubule where all of the renal glutamine synthase and the highest level of alanine aminotransferase are located. Thus alanine and glutamine could be produced when the ammonia was not needed to neutralize excess acidity.
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PMID:Branched-chain amino acid aminotransferase along the rabbit and rat nephron. 287 Dec 15

The activities of alanine and aspartate transaminases, adenylate deaminase, glutamine synthetase and glutamate and xanthine dehydrogenases have been measured in liver, yolk sac membrane, intestine and breast and leg muscle of domestic fowl hatchlings receiving for 3 or 5 days either a standard diet or hard boiled eggwhite as well as in 3 or 5 days starved animals. The patterns of activation of amino acid metabolism enzymes were fully comparable in protein-fed and starved groups with respect to fed controls; the differences with respect to the latter became more marked in 5- than in 3-days old chicks. In 5-days old chicks intestine alanine transaminase activity increased in parallel to that of liver in protein-fed animals but not in those starved, in agreement with an enhanced alanine transfer between both organs under this situation. Both, starvation and protein-feeding, induced a general decrease in the amino acid metabolizing ability of muscle. Glutamine (but not alanine) synthetizing capabilities were enhanced.
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PMID:Effect of starvation and a protein diet on the amino acid metabolism enzyme activities of the organs of domestic fowl hatchlings. 287 42

The present investigation revealed the effect of the organochlorine insecticide dieldrin at the dose level 0.25 LD50 at different time intervals on the concentration of 11 rat brain amino acids, on the activities of glutamic oxyacetic transaminase (GOT), glutamic pyruvic transaminase (GpT) and cholinesterase. The study was also extended to include the total protein content during the tested periods. The daily injection of dieldrin caused a marked decrease in the levels of glutamic acid, glutamine and taurine and an increase in the levels of aspartic acid, asparagine, GABA, glycine, lysine, serine, alanine and histidine. However, the maximal increase and decrease were recorded for most of the tested amino acids at the end of the tested period. The activity of the transaminases increased significantly. The recorded values of GOT were usually higher than GPT. Cholinesterase activity was inhibited thoroughly during all the experimental periods. Total protein content was decreased in the experiment; the minimal value was given 3 days after the injection.
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PMID:Effect of dieldrin injection on the level of certain amino acids and some enzymes in rat brain. 287 4

The short-term metabolic fate of [13N]ammonia in the livers of adult male, anesthetized rats was determined. Following a bolus injection of tracer quantities of [13N]ammonia into the portal vein, the single pass extraction was approximately 93%, in good agreement with the portal-hepatic vein difference of approximately 90%. High performance liquid chromatographic analysis of deproteinized liver samples indicated that labeled nitrogen is exchanged rapidly among components of: mitochondrial aspartate aminotransferase and glutamate dehydrogenase reactions and cytoplasmic aspartate aminotransferase and alanine aminotransferase reactions (t1/2 for the exchange of label toward equilibrium is on the order of seconds). Comparison of specific activities of glutamate and ammonia suggests that at 5 s most labeled glutamate was mitochondrial, whereas at 60 s approximately 93% was cytosolic; this change is presumably brought about by the combined action of the mitochondrial and cytosolic aspartate aminotransferases and the aspartate carrier of the malate-aspartate shuttle. Specific activity measurements of glutamate, alanine, and aspartate are in accord with the proposal by Williamson et al. (Williamson, D.H., Lopes-Vieira, O., and Walker, B. (1967) Biochem. J. 104, 497-502) that the components of the aspartate aminotransferase reaction are in thermodynamic equilibrium, whereas the components of the alanine aminotransferase reaction are in equilibrium but compartmented in the rat liver. Despite considerable label in citrulline at early time points, no radioactivity (less than or equal to 0.25% of the total) was detected in carbamyl phosphate, suggesting very efficient conversion to citrulline with little free carbamyl phosphate accumulating in the mitochondria. Our data also show that some portal vein-derived ammonia is metabolized to glutamine in the rat liver, but the amount is small (approximately 7% of that metabolized to urea) in part because liver glutamine synthetase is located in a small population of perivenous cells "downstream" from the urea cycle-containing periportal cells. Finally, no tracer evidence could be found for the participation of the purine nucleotide cycle in ammonia production from aspartate. The present work continues to emphasize the usefulness of [13N]ammonia for short-term metabolic studies under truly tracer conditions, particularly when turnover times are on the order of seconds.
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PMID:Short-term metabolic fate of [13N]ammonia in rat liver in vivo. 287 38


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