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)

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

Leucine and monomethyl succinate initiate insulin release, and glutamine potentiates leucine-induced insulin release. Alanine enhances and malate inhibits leucine plus glutamine-induced insulin release. The insulinotropic effect of leucine is at least in part secondary to its ability to activate glutamate oxidation by glutamate dehydrogenase (Sener, A., Malaisse-Lagae, F., and Malaisse, W. J. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 5460-5464). The effect of these other amino acids or Krebs cycle intermediates on insulin release also correlates with their effects on glutamate dehydrogenase and their ability to regulate inhibition of this enzyme by alpha-ketoglutarate. For example, glutamine enhances insulin release and islet glutamate dehydrogenase activity only in the presence of leucine. This could be because leucine, especially in the presence of alpha-ketoglutarate, increases the Km of glutamate and converts alpha-ketoglutarate from a noncompetitive to a competitive inhibitor of glutamate. Thus, in the presence of leucine, this enzyme is more responsive to high levels of glutamate and less responsive to inhibition by alpha-ketoglutarate. Malate could decrease and alanine could increase insulin release because malate increases the generation of alpha-ketoglutarate in islet mitochondria via the combined malate dehydrogenase-aspartate aminotransferase reaction, and alanine could decrease the level of alpha-ketoglutarate via the alanine transaminase reaction. Monomethyl succinate alone is as stimulatory of insulin release as leucine alone, and glutamine enhances the action of both. Succinyl coenzyme A, leucine, and GTP are all bound in the same region on glutamate dehydrogenase, where GTP is a potent inhibitor and succinyl coenzyme A and leucine are comparable activators. Thus, the insulinotropic properties of monomethyl succinate could result from it increasing the level of succinyl coenzyme A and decreasing the level of GTP via the succinate thiokinase reaction.
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PMID:Regulation of insulin release by factors that also modify glutamate dehydrogenase. 304 28

The mechanism by which pentylenetetrazole provokes convulsions in animals has been investigated by measuring its influence in vitro on the activities of several enzymes of glutamate metabolism in rat brain homogenates. Pentylenetetrazole does not affect the specific activities of glutamine synthetase, glutaminase, or glutamate decarboxylase; it inhibits those of glutamate dehydrogenase and aspartate aminotransferase, and stimulates that of gamma-aminobutyric acid (GABA) aminotransferase. The overall consequence of the action of pentylenetetrazole on the activities of these enzymes should be an increase in the concentration of glutamate and a decrease in that of GABA. This modulation of glutamate and GABA metabolism by pentylenetetrazole could contribute to the triggering of convulsions.
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PMID:Pentylenetetrazole inhibits glutamate dehydrogenase and aspartate aminotransferase, and stimulates GABA aminotransferase in homogenates from rat cerebral cortex. 321 59

The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.
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PMID:Effect of hypoxia, aging and pharmacological treatment on muscular metabolites and enzyme activities. 322 9

Molecular mass, Stoke's radius, frictional coefficient and isomer-type of non-denatured proteins can be obtained by time-dependent gradient gel electrophoresis by evaluating the resulting data using a two-step mathematical procedure. Provided a histochemical staining procedure is available to locate the position of an enzyme in the gel, crude cell extracts can be used for estimating their molecular size properties. The computation of molecular properties of non-denatured proteins is demonstrated for isozymes of aspartate aminotransferase (EC 2.6.1.1), peroxidase (EC 1.11.1.42) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) from current-year needles of spruce. The resulting data as well as those which were calculated for esterase (EC 3.1.1.1), glutamate dehydrogenase (EC 1.4.1.4), isocitrate dehydrogenase (EC 1.4.1.42), and shikimate dehydrogenase (EC 1.1.1.25) are in accordance with those reported in the literature. The method described may be applied to various scientific areas such as genetics or environmental pollution. It could be shown here that current-year needles of injured spruce (damage class 3) contained two more peroxidase isozymes and one more glucose-6-phosphate dehydrogenase isozyme than those from non-injured trees. These differences may mark two genotypes of spruce of different susceptibilities towards present-day air and soil pollutants.
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PMID:Determination of molecular mass, Stokes' radius, frictional coefficient and isomer-type of non-denatured proteins by time-dependent pore gradient gel electrophoresis. 323 69

The net production of citrate from exogenous substrates by rat ventral prostate was investigated. The preparation of isolated prostate epithelial cells was described. These cells were capable of oxidizing pyruvate (5 mmol/l) as a source of acetyl coenzyme A. The addition of aspartate + alpha-ketoglutarate (5 mmol/l) in the presence of pyruvate resulted in significant net production of citrate and excess oxalacetate. In the presence of aspartate and glutamate, the cells were capable of producing citrate without excessive oxalacetate production. Neither glucose alone nor glucose plus pyruvate resulted in net citrate production. The results demonstrated that aspartate could serve as a 4-carbon source of oxalacetate for citrate synthesis. Furthermore, the results indicate the intramitochondrial operation of a glutamate-aspartate-citrate pathway involving mitochondrial aspartate aminotransferase and glutamic dehydrogenase activities in prostate epithelial cells.
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PMID:Net citrate production by isolated prostate epithelial cells. 337 41

There were significant changes in enzyme activities and concentrations of metabolites in the blood and liver of cows with fatty livers when compared to normal cows. Blood and liver samples were taken from cows at the abattoir immediately after slaughter. The liver was checked for pathological signs and the samples were divided according to the degree of fatty changes. Three groups were studied: controls showing no gross pathological signs, mild fatty infiltration and severe infiltration. In cows with fatty liver, there were significant increases in the serum activities of isocitric dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), glutamic dehydrogenase (GLDH), lactic dehydrogenase (LDH), malic dehydrogenase (MDH), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). In the fatty liver, the activities of the enzymes, ICDH, G6PDH, LDH, MDH, ALP and malic enzyme (ME) were significantly higher, while sorbitol dehydrogenase (SDH) was significantly lower. While serum total lipid decreased, the opposite was seen in the liver with higher lipid content, mainly due to triglycerides and cholesterol esters. The significant increases in the NADPH generating enzymes ME, ICDH, G6PDH and MDH, which are required for fatty acid synthesis, suggest that the lipids accumulated in the liver are not only of extrahepatic origin, mobilized into the liver, but also arise from increased lipid synthesis in the liver which is induced during the laying down of fat in the liver. Measurement of the serum NADPH generating enzymes may serve as a useful biochemical test specific for fatty liver in cows.
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PMID:Biochemical changes associated with the fatty liver syndrome in cows. 339 48

The assay of cerebrospinal fluid (CSF) enzymes has been suggested for assessing the extent of damage and patient prognosis in cases of brain injury. A potential difficulty associated with using CSF enzyme levels as predictors of outcome is the possibility that enzyme concentrations may vary substantially from one brain region to another. We have determined the concentrations of seven enzymes in seven brain regions in the rat and cat. Acid phosphatase (ACP), aspartate aminotransferase (AST), isocitrate dehydrogenase (ICDH), lactate dehydrogenase (LD), and malate dehydrogenase (MDH) show little regional variability in the rat and cat while creatine kinase (CK) and glutamate dehydrogenase (GDH) both exhibit considerable regional variability in both animals. Lack of correlation between CSF enzyme levels and prognosis may possibly be explained by the observed regional variability. The enzymes demonstrating more homogeneous concentrations throughout the brain may be better candidates for predicting patient outcome by determination of the CSF enzyme level.
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PMID:The regional variability of enzymes in the brain: relevance to CSF enzyme determinations. 341 84


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