Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simplified method was developed for the bulk separation of neuronal perikarya and astroglial cells from adult rat brain without the involvement of density gradients. Activities of various enzymes involved in glutamate metabolism were estimated and compared with those of synaptosomes. The activities of glutamate dehydrogenase and aspartate aminotransferase were higher in synaptosomes than in neuronal perikarya or glia. Glutamine synthetase was distributed in all the three fractions while glutaminase activity was higher in astrocytes than in synaptosomes and was not detectable in neuronal perikarya. The significance of these results in relation to metabolic compartmentation was discussed.
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PMID:Isolation of astrocytes, neurons, and synaptosomes of rat brain cortex: distribution of enzymes of glutamate metabolism. 285 36

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

Activity levels of the enzymes of glutamate metabolism were determined in the neuronal perikarya and synaptosomes isolated from the cerebral cortex of normal and hyperammonemic rats. In neuronal perikarya, the activities of glutamate dehydrogenase, aspartate, alanine aminotransferases and glutamine synthetase were elevated in hyperammonemic states. In synaptosomes, glutamate dehydrogenase and aspartate aminotransferase were suppressed, while glutamine synthetase and glutaminase were elevated. These results suggested the involvement of neuronal perikarya in ammonia detoxification at least in acute hyperammonemic states.
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PMID:Differential response of enzymes of glutamate metabolism in neuronal perikarya and synaptosomes in acute hyperammonemia in rat. 286 71

The relationship between nitrogen assimilation, metabolism and aflatoxin formation has been investigated in a toxigenic and a non-toxigenic strain of Aspergillus parasiticus. Ammonia from the medium is mainly assimilated via NADP-requiring glutamate dehydrogenase. During growth NAD-requiring glutamate dehydrogenase followed an inverse pattern of activity with respect to NADP glutamate dehydrogenase. Alpha-ketoglutarate, the product of NAD glutamate dehydrogenase, stimulated acetate incorporation into aflatoxins. Glutamine synthetase, ornithine transcarbamylase, both utilizing glutamate as substrate were assayed under different growth conditions. An important regulatory role for glutamine synthetase is suggested. The metabolic route of asparagine utilization was also investigated. Both the known pathways, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase are operative simultaneously.
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PMID:Nitrogen metabolism in Aspergillus parasiticus NRRL 3240 and A. flavus NRRL 3537 in relation to aflatoxin production. 287 96

Activity of enzymes participating in metabolism of glutamate and content of nicotinamide nucleotides was studied in rat liver tissue within 24 hrs after intramuscular administration of alpha-tocopheryl acetate at doses of 30 mg and 300 mg per kg of body mass. Excess of the vitamin was responsible for a decrease in the ratio NAD+/NADH in cytosol, for stimulation of glutamate dehydrogenase reaction, for a decrease of aspartate aminotransferase activity in mitochondria and of alanine aminotransferase activity in cytosol as well as for an increase of NADPH content.
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PMID:[Effect of alpha-tocopherol on glutamic acid metabolism and nicotinamide coenzyme levels in hepatocytes]. 287 84

6-Aminonicotinamide (6-AN), an antimetabolite of pyridine nucleotide synthesis, caused time dependent and regionally selective changes in the activities of the enzymes related to glutamate metabolism in the brain. The NAD+- and NADP+-linked glutamate dehydrogenase showed opposite pattern of changes in cerebellum, whereas cerebral hemispheres and brain stem exhibited similar response. Glutamate oxaloacetate transaminase (aspartate aminotransferase) and malate dehydrogenase, the functional enzymes of malate-aspartate shuttle, were decreased in soluble fraction of cerebral hemispheres and increased significantly in cerebellum after 16 hours of drug administration. Glutamate pyruvate transaminase (alanine aminotransferase) also showed an increase in the activity in cerebellum and brain stem after 8 hours of drug treatment. The EEG patterns obtained from 6-AN treated animals showed periodic bursts, turning to convulsive polyspike activity between 8-16 hours, indicating the onset of comatose-like stage. The results indicate that glutamate metabolism offers considerable anaplerotic potentials following impaired energy state after 6-AN treatment.
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PMID:6-Aminonicotinamide: EEG changes and effects on the activities of enzymes related to glutamate metabolism in rat brain regions. 287 43

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

Pathways of glutamine metabolism in resting and proliferating rat thymocytes were evaluated by in vitro incubations of freshly prepared or 60-h cultured cells for 1-2 h with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76 and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for 25 and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in both cells is transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37 and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations.
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PMID:Pathways of glutamine and glutamate metabolism in resting and proliferating rat thymocytes: comparison between free and peptide-bound glutamine. 288 73

The metabolism of [15N]glutamate was studied with gas chromatography-mass spectrometry in rat brain synaptosomes incubated with and without glucose. [15N]Glutamate was taken up rapidly by the preparation, reaching a steady-state level in less than 5 min. 15N was incorporated predominantly into aspartate and, to a much lesser extent, into gamma-aminobutyrate. The amount of [15N]ammonia formed was very small, and the enrichment of 15N in alanine and glutamine was below the level of detection. Omission of glucose substantially increased the rate and amount of [15N]aspartate generated. It is proposed that in synaptosomes (a) the predominant route of glutamate nitrogen disposal is through the aspartate aminotransferase reaction; (b) the aspartate aminotransferase pathway generates 2-oxoglutarate, which then serves as the metabolic fuel needed to produce ATP; (c) utilization of glutamate via transamination to aspartate is greatly accelerated when flux through the tricarboxylic acid cycle is diminished by the omission of glucose; (d) the metabolism of glutamate via glutamate dehydrogenase in intact synaptosomes is slow, most likely reflecting restriction of enzyme activity by some unknown factor(s), which suggests that the glutamate dehydrogenase reaction may not be near equilibrium in neurons; and (e) the activities of alanine aminotransferase and glutamine synthetase in synaptosomes are very low.
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PMID:Glucose and synaptosomal glutamate metabolism: studies with [15N]glutamate. 290 Aug 79

We recently described a preferential reduction of the secretory response to nutrient secretagogues (glucose; leucine plus glutamine) in islets maintained in culture after in vitro exposure to streptozotocin (SZ). The present study is an attempt to further clarify the biochemical mechanisms behind this defective insulin response. Mouse pancreatic islets were collagenase isolated and, after 4-5 days in culture, exposed during 30 min at 37 C to 1.8 mM SZ or vehicle alone (controls). The islets were subsequently cultured for 7 days in medium RPMI 1640 plus 10% calf serum, before the enzymatic and metabolic studies were performed. The activities of the glycolytic enzymes, hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in the control and SZ-exposed islets. The relative amount of cytosolic and mitochondria-bound hexokinase was also unaffected by SZ. However, there was a 30-40% decrease in the activity of NAD+- and NADP+-dependent glutamate dehydrogenase and glutamate-aspartate transaminase in the SZ-treated islets. This coincided with a 40% decrease in L-[U-14C]glutamine oxidation in the SZ-treated islets. The D-glucose catabolism was further examined in the presence of D-[5-3H] and D-[6-14C] glucose. There was no difference between control and SZ islets in terms of glucose utilization at either 1.7 or 16.7 mM glucose. The oxidation of D-[6-14C]glucose was nevertheless decreased by more than 50% in SZ islets incubated at 16.7 mM (but not 1.7 mM) glucose. Altogether, these converging observations suggest a perturbation of distal regulatory processes, apparently at the mitochondrial level, in the D-glucose and L-glutamine catabolism of SZ-exposed islets. Whether this reflects a primary action of SZ on the islet mitochondria, or an inhibitory effect of SZ on the synthesis of mitochondrial enzymes, as a result of nuclear DNA damage, remains to be elucidated.
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PMID:Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. 296 23


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