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: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebral metabolic effects of 2.5, 5, 7.5, 10, 20, 30 and 60 min exposure to 1% CO were studied in lightly anesthetized rats by measurement of cerebral cortical contents of selected glycolytic and citric acid cylce intermediates, as well as tissue energy phosphates. The initial change in the glycolytic sequence occurred at 2.5 min with decreases in tissue glucose and glucose-6-phosphate and increases in fructose-1-6-diphosphate which indicated an activation of phosphofructokinase and hexokinase. The "crossover" pattern between glucose-6-phosphate and fructose-1,6-diphosphate was present at 5, 7.5 and 10 min, but not at 20, 30 and 60 min and thus confirmed previous observations that detection of phosphofructokinase activation in acute unifactorial cerebral hypoxia requires tissue study during the early phases of the experimental exposure. The initial activation of phosphofructokinase occurred in the absence of detectable changes in the tissue content of ATP, ADP, AMP or phosphocreatine and therefore suggested that an imbalance of tissue energy homeostasis is not a prerequisite for the activation of glycolysis in CO intoxication. One percent CO resulted in an increasing malate/oxaloacetate ratio at 5 min, followed by a decrease in alpha-ketoglutarate and aspartate at 7.5 min which suggested a shift in the aspartate aminotransferase reaction towards the replenishment of oxaloacetate removed via the malate dehydrogenase reaction. Subsequent increases in alpha-ketoglutarate at 10, 20, 30 and 60 min were associated with increases in alanine, indicating a contributing role for a secondary shift of the alanine aminotransferase reaction in the replenishment of alpha-ketoglutarate. A comparison of the CO induced changes in the glycolytic and citric acid cycle pathways with those seen in acute hypoxemia indicates no basic qualitative differences in the metabolic responses of brain tissue to the two conditions.
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PMID:Cerebral carbohydrate metabolism during acute carbon monoxide intoxication. 1 62

Lactate production by liver slices from fetal rats (17th--18th day of gestation) is enhanced about two fold by aminooxyacetate, an inhibitor of aspartate transaminase (EC 2.6.1.1). Such an effect is consistent with an increase of the cytosolic NAD-redox state owing to the parallel fall in the pyruvate level, whereas the glycolytic flux does not seem to be influenced appreciably. Indeed, although the inhibitor causes a marked increase of fructose 1,6-diphosphate, glucose-6-phosphate decreases only slightly. These results suggest that in fetal rat liver the malate-aspartate shuttle is operative in the reoxidation of cytosolic NADH produced during aerobic glycolysis.
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PMID:The operation of the malate-aspartate shuttle in the reoxidation of glycolytic NADH in slices of fetal rat liver. 20 12

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6 phosphate glucono dehydrogenase (6 phospho-D-gluconate: NADP oxidoreductase, 6PGD) lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH), glutamate oxaloacetate transaminase (L-aspartate: 2-oxo-glutarate aminotransferase, GOT) and hexokinase (ATP: D-hexo-6-phosphotrans-ferase, Hx) were measured over 24 h in isolated lymphocytes of normal subjects and in white cells of patients with chronic lymphatic leukaemia (CLL). The activitty patterns of all enzymes in the normal lymphocytes were similar. A computed pattern of all the results exhibited a circadian rhythm of activity with the highest level at 16.00 hours. The oscillations in the activities of the same enzymes in the CLL cells differed among the patients, although all the enzymes of the same individual showed a similar diurnal rhythmic pattern. All peaks in this group appeared between 20.00 and 08.00 hours. The possible importance of these observations in setting up therapeutic schedules was raised.
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PMID:Blood leucocyte enzymes. III. Diurnal rhythm of activity in isolated lymphocytes of normal subjects and chronic lymphatic leukaemia patients. 98 50

The activities of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, G6PD), 6-phosphogluconate dehydrogenase (6-phospho-D-gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D-hexose 6-phosphotransferase, Hx), lactate dehydrogenase (D-lactate: NAD oxidoreductase, LDH). glutamate oxaloacetate transaminase (L-aspartate: 2 oxoglutarate aminotransferase, GOT) and dihydrofolate reductase (DHFR) were measured at 8 a.m. in leucocytes of healthy individuals and patients with chronic myeloid leukaemia (CML), chronic lymphatic leukaemia (CLL), myelofibrosis with myeloid metaplasia and polycythaemia vera. In view of the heterogeneity of the leucocyte populations in these conditions, the enzyme activities were correlated to the number of immature cells in CML and to the percentage of lymphocytes in CLL. No differences in the enzyme activities were found between the white cells of healthy individuals, myelofibrosis with myeloid metaplasia and polycythaemia vera. In CML the activities of all enzymes except GOT correlated directly with the number of immature cells; an inverse correlation with the number of lymphocytes was observed in CLL. GOT was the only enzyme whose activity correlated with the number of lymphocytes in the cell suspension. Furthermore, a significantly higher activity of this enzyme was found in Ficoll-isolated CLL lymphocytes as compared to normal lymphocytes.
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PMID:Blood leucocyte enzymes. II. Activities at 8-9 a.m. in cells of normal subjects, chronic lymphatic leukaemia and chronic myeloid leukaemia patients. 105 70

Five enzymes were measured in 50 liver specimens (18 normal liver, 20 Reye liver, 12 diverse liver disorders other than Reye syndrome). The enzymes were: glutamic dehydrogenase (E.C. 1.4.1.3), monoamine oxidase (E.C. 1.4.3.4), lactate dehydrogenase (E.C. 1.1.1.27), D-glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49), catalase (E.C. 1.11.1.6). The Reye syndrome group showed significant decreases in glutamic dehydrogenase (56%) and monoamine oxidase (70%) compared to normal control tissue and these changes were not characteristic of the non-Reye liver disorder group as a whole. Neither catalase nor lactate dehydrogenase appeared to be altered significantly in the Reye or in the abnormal control group compared with normal controls. Thus, only the prominent decreases in the mitochondrial enzyme activities appeared to be highly characteristic of Reye syndrome. Paradoxically, the means of the five hepatic enzymes and the admission levels of two serum enzymes indicative of liver damage (alanine and aspartate aminotransferase) were remarkably similar for both survivors and nonsurvivors of Reye syndrome.
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PMID:Quantitative evaluation of the extent of hepatic enzyme changes in Reye syndrome compared with normal liver or with non-Reye liver disorders: objective criteria for animal models. 396 10

The cerebral metabolic effects of intravenous administration of 1000 mg/kg gamma-hydroxybutyrate (GHB) were studied by sequential measurement of the cerebral contents of selected glycolytic-citric acid cycle intermediates and energy phosphates in lightly anesthetized rats. The initial change in the glycolytic pathway occurred by 2.5 min, with increases of tissue glucose-6-phosphate and decreases of fructose-1,6- diphosphate which indicated an inhibition of phosphofructokinase. This pattern was transient and was replaced at 5--15 min by increasing tissue glucose and decreasing glucose-6-phosphate which indicated an inhibition of hexokinase. The initial inhibition of phosphofructokinase was associated with functional depression, an isoelectric EEG and an increase of the tissue phosphocreatine which suggested that the observed metabolic pattern was an adaptation to the reduced energy needs of neuronal depression. Within 2.5 min of GHB injection tissue alpha-ketoglutarate and aspartate showed significant increases which suggested a shift in the aspartate aminotransferase reaction. Preliminary calculations indicated that the probable cause of this shift was an increase in oxaloacetate content due to GHB oxidation. The cytoplasmic NADH/NAD+ ratio remained unchanged throughout the entire exposure to GHB (2.5--180 min) and thus gave no support for the hypothesis that GHB interfers with glycolysis via the restriction of free cytoplasmic NAD+ required for the glyceraldehyde phosphate dehydrogenase step.
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PMID:Sequential alterations of cerebral carbohydrate metabolism associated with gamma-hydroxybutyrate. 735 98

Cytosolic aspartate aminotransferase (cAspAT) participates in gluconeogenesis in the liver and is expected to exert a glyceroneogenic function in the adipose tissue when the supply of glucose is limited. Here we demonstrate that adipose cAspAT messenger RNA (mRNA) is increased when rats are fed a low carbohydrate diet. In the 3T3-F442A, BFC-1 adipocyte cell lines and differentiated adipocytes in primary culture, a 24 h glucose deprivation induces approximately a 4-fold increase in cytosolic AspAT (cAspAT) mRNA, whereas mitochondrial AspAT mRNA remains unchanged. cAspAT activity is also increased in a weaker but reproducible manner. Addition of glucose within a physiological range of concentrations reverses the increase of cAspAT mRNA in 8 h (EC50 = 1.25 g/liter). Such a regulation requires protein synthesis and is specific for adipocytes differentiated in culture. It does not occur in Fao or H4IIE hepatoma cells, in C2 muscle cells, or in 293 kidney cells. 2-deoxyglucose mimicks glucose, while 3-orthomethyl-glucose has no effect, suggesting that glucose-6-phosphate is the effector. cAspAT mRNA stability is not affected by glucose deprivation. To ascertain the transcriptional nature of the glucose effect, we have stably transfected 3T3-F442A adipoblasts with constructs containing the chloramphenicol acetyltransferase reporter gene under the control of either 5'-deletions of the cAspAT gene promoter or internal fragments in an heterologous context. We demonstrate that a glucose response element(s) is present in the region between -1838 and -1702 bp relative to the translation start site. In this region, three DNA sequences bind nuclear proteins from adipocytes as shown by footprinting experiments. Our results indicate that cAspAT gene transcription is repressed by glucose selectively in adipocytes.
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PMID:Identification of an adipocyte-specific negative glucose response region in the cytosolic aspartate aminotransferase gene. 983 31

This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.
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PMID:Antioxidant potential of Cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity. 2150 74

Lactate and ammonia are the most important waste products of central carbon metabolism in mammalian cell cultures. In particular during batch and fed-batch cultivations these toxic by-products are excreted into the medium in large amounts, and not only affect cell viability and productivity but often also prevent growth to high cell densities. The most promising approach to overcome such a metabolic imbalance is the replacement of one or several components in the culture medium. It has been previously shown that pyruvate can be substituted for glutamine in cultures of adherent Madin-Darby canine kidney (MDCK) cells. As a consequence, the cells not only released no ammonia but glucose consumption and lactate production were also reduced significantly. In this work, the impact of media changes on glucose and glutamine metabolism was further elucidated by using a high-throughput platform for enzyme activity measurements of mammalian cells. Adherent MDCK cells were grown to stationary and exponential phase in six-well plates in serum-containing GMEM supplemented with glutamine or pyruvate. A total number of 28 key metabolic enzyme activities of cell extracts were analyzed. The overall activity of the pentose phosphate pathway was up-regulated during exponential cell growth in pyruvate-containing medium suggesting that more glucose-6-phosphate was channeled into the oxidative branch. Furthermore, the anaplerotic enzymes pyruvate carboxylase and pyruvate dehydrogenase showed higher cell specific activities with pyruvate. An increase in cell specific activity was also found for NAD(+)-dependent isocitrate dehydrogenase, glutamate dehydrogenase, and glutamine synthetase in MDCK cells grown with pyruvate. It can be assumed that the increase in enzyme activities was required to compensate for the energy demand and to replenish the glutamine pool. On the other hand, the activities of glutaminolytic enzymes (e.g., alanine and aspartate transaminase) were decreased in cells grown with pyruvate, which seems to be related to a decreased glutamine metabolism.
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PMID:Metabolic adaptation of MDCK cells to different growth conditions: effects on catalytic activities of central metabolic enzymes. 2161 69

Microalgae are a promising feedstock for biofuel production. Microalgal metabolic pathways are heavily influenced by environmental factors. For instance, lipid metabolism can be induced by nitrogen-limiting conditions. However, the underlying mechanisms of lipid biosynthesis are unclear. In this study, we analyzed the global metabolic profiles of three genetically closely related Chlorella strains (C1, C2, and C3) with significant differences in lipid productivity to identify the contributions of key metabolic pathways to lipid metabolism. We found that nitrogen obtained from amino acid catabolism was assimilated via the glutamate-glutamine pathway and then stored as amino acids and intermediate molecules (particularly proline, alanine, arginine, succinate, and gamma-aminobutyrate) via the corresponding metabolic pathways, which led to carbon-nitrogen disequilibrium. Excess carbon obtained from photosynthesis or glycolysis was re-distributed into carbon-containing compounds, such as glucose-6-phosphate, fructose-6-phosphate, phosphoenolpyruvate, lactate, citrate, 3-hydroxybutyrate, and leucine, and then diverted into lipid metabolism for the production of storage lipids via the gamma-aminobutyrate pathway, glycolysis, and the tricarboxylic acid cycle. These results were substantiated in the model green alga Chlamydomonas reinhardtii by analyzing various mutants deficient in glutamate synthase/NADH-dependent, glutamate synthase/Fd-dependent, glutamine synthetase, aspartate aminotransferase, alanine aminotransferase, pyruvate kinase, and citrate synthase. Our study suggests that not only carbon but also nitrogen assimilation and distribution pathways contribute to lipid biosynthesis. Furthermore, these findings may facilitate genetic engineering efforts to enhance microalgal biofuel production.
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PMID:Comparative metabolic profiling of the lipid-producing green microalga Chlorella reveals that nitrogen and carbon metabolic pathways contribute to lipid metabolism. 2863 Jun 48


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