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)

1)The time course of changes in concentration of renal metabolites in response to a non-toxic load of NH4 as NH4 Cl or NH4HCO3 were measured in fasted rats. 2) Following a NH4Cl load, decrease of renal concentration of 2-oxoglutarate occurs but this change is delayed in relation to the peak of the blood ammonia concentration and persists after disappearance of the hyperammoniemia. 3) Following a NH4HCO3 load, the oxoglutarate concentration changes are less marked and more transient. 4) No close relationship between the mitochondrial free NAD/NADH ratio calculated from the glutamate dehydrogenase and the 3-hydroxybutyrate dehydrogenase systems were seen during alteration of the ammonia concentration. 5) Contrary to the observations in the liver under similar circumstances (BROSNAN, J.T. et al.: Biochem.J. 138, 453, 1974), no increase in kidney tissue or renal venous blood alanine or aspartate concentration are seen. 6) A constant infusion of NH4HCO3 resulted only in an increase in tissue and renal venous blood glutamine concentration. 7) The infusion of NH4 together with a carbon source (malate) resulted in a similar increase in tissue glutamine concentration and more striking increase in renal venous glutamine concentration. No accumulation of aspartate nor alanine were seen. 8) In vitro studies indicate that the net flux through both the aspartate aminotransferase and the glutamate dehydrogenase reactions is dependent on the concentration of the reactants as expected for a near-equilibrium system. 9) It is concluded that the kidney response to an ammonia load differs from that of the liver despite the existence of a similar network of near-equilibrium reactions of (1) a lack of local availability of oxaloacetate, (2) a lower activity of alanine aminotransferase, (3) a greater in vivo activity of glutamine synthetase.
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PMID:Effect of an ammonia load on the kidney near-equilibrium systems in the rat in vivo. 18 80

1. The mechanism of L-cysteinesulfinate permeation into rat liver mitochondria has been investigated. 2. Mitochondria do not swell in ammonium or potassium salts of L-cysteinesulfinate in all the conditions tested, including the presence of valinomycin and/or carbonylcyanide p-trifluoromethoxyphenylhydrazone. 3. The activation of malate oxidation by L-cysteinesulfinate is abolished by aminooxyacetate, an inhibitor of the intramitochondrial aspartate aminotransferase, it is not inhibited by high concentrations of carbonylcyanide p-trifluoromethoxyphenylhydrazone (in contrast to the oxidation of malate plus glutamate) and it is decreased on lowering the pH of the medium. 4. All the aspartate formed during the oxidation of malate plus L-cysteinesulfinate is exported into the extramitochondrial space. 5. Homocysteinesulfinate, cysteate and homocysteate, which are all good substrates of the mitochondrial aspartate aminotransferase, are unable to activate the oxidation of malate. Homocysteinesulfinate and homocysteate have no inhibitory effect on the L-cysteinesulfinate-induced respiration, whereas cysteate inhibits it competitively with respect to L-cysteinesulfinate. 6. In contrast to D-aspartate, D-cysteinesulfinate and D-glutamate, L-aspartate inhibits the oxidation of malate plus L-cysteinesulfinate in a competitive way with respect to L-cysteinesulfinate. Vice versa, L-cysteinesulfinate inhibits the influx of L-aspartate. 7. Externally added L-cysteinesulfinate elicits efflux of intramitochondrial L-aspartate or L-glutamate. The cysteinesulfinate analogues homocysteinesulfinate, cysteate and homocysteate and the D-stereoisomers of cysteinesulfinate, aspartate and glutamate do not cause a significant release of internal glutamate or aspartate, indicating a high degree of specificity of the exchange reactions. External L-cysteinesulfinate does not cause efflux of intramitochondrial Pi, malate, malonate, citrate, oxoglutarate, pyruvate or ADP. The L-cysteinesulfinate-aspartate and L-cysteinesulfinate-glutamate exchanges are inhibited by glisoxepide and by known substrates of the glutamate-aspartate carrier. 8. The exchange between external L-cysteinesulfinate and intramitochondrial glutamate is accompanied by translocation of protons across the mitochondrial membrane in the same direction as glutamate. The L-cysteinesulfinate-aspartate exchange, on the other hand, is not accompanied by H+ translocation. 9. The ratios delta H+/delta glutamate, delta L-cysteinesulfinate/delta glutamate and delta L-cysteinesulfinate/delta aspartate are close to unity. 10. It is concluded that L-cysteinesulfinate is transported by the glutamate-aspartate carrier of rat liver mitochondria. The present data suggest that the dissociated form of L-cysteinesulfinate exchanges with H+-compensated glutamate or with negatively charged aspartate.
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PMID:The transport of L-cysteinesulfinate in rat liver mitochondria. 48 67

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

1. Isolated hepatocytes were used to establish the reasons for the accumulation of aspartate, previously observed when the isolated rat liver was perfused with ethanol in the presence of alanine or ammonium lactate. 2. The isolated cells did not form aspartate when incubated with alanine and ethanol, but much aspartate was formed on incubation with ammonium lactate and ethanol. 3. Urea was the main nitrogenous product on incubation with alanine, in contrast with the perfused liver, where major quantities of NH4+ are also formed. When the formation of urea was nullified by the addition of urease, alanine plus ethanol caused aspartate formation, indicating that aspartate formation depends on the presence of critical concentrations of NH4+. 4. The accumulated aspartate was present in the cytosol. Ethanol halved the content of 2-oxoglutarate in the cytosol and more than trebled that of glutamate in the mitochondria. 5. The findings support the assumption that 2-oxoglutarate formed by the mitochondrial aspartate aminotransferase is not translocated to the cytosol in the presence of ethanol and NH4+, because it is rapidly converted into glutamate, the dehydrogenation of ethanol providing the required NADH. Aspartate, however, is translocated to the cytosol and accumulates there because of the lack of stoicheiometric amounts of oxoglutarate.
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PMID:The accumulation of aspartate in the presence of ethanol in rat liver. 120 Oct 7

Photometric-kinetic methods for the determination of activity of aspartate aminotransferase are proposed. The flow-injection manifold used for this purpose includes a selecting valve which allows the sample to be trapped in a closed circuit where a solid reactor housing an auxiliary enzyme and a conventional single detector allows a multipeak recording to be obtained for each sample. This record represents a typical kinetic curve from which much information can be obtained to develop fixed-time and reaction-rate methods for the determination of the analyte based on its catalytic action on the L-aspartic acid-2 oxoglutarate system. The linear range is found to be between 1 and 500 U l-1, with relative standard deviation less than 1%. The utility of the methods is illustrated by the determination of the analyte in human serum from healthy and sick individuals.
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PMID:Kinetic determination of aspartate aminotransferase in human serum with a flow-injection/multidetection system. 182 Nov 42

A new spectrophotometric procedure is described for determining glutamate-dependent activities of aspartate aminotransferase, alanine aminotransferase, and ornithine aminotransferase with NADPH-linked glutamate dehydrogenase (GDH) from nitrate-grown Stichococcus bacillaris. The algal NADPH-GDH is highly specific for oxoglutarate and can catalyze the reduction of this keto acid in the presence of high glutamate concentrations, and thus is suitable for the measurement of oxoglutarate produced in glutamate-dependent amino-transferase reactions. The alga produces large amounts of NADPH-GDH which can be adequately purified in a few simple steps. The purified enzyme can be stored at 4 degrees C for several weeks without any detectable loss of activity. The algal NADPH-GDH can also be used for the estimation of small amounts of oxoglutarate in aqueous extracts.
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PMID:A spectrophotometric procedure for measuring oxoglutarate and determining aminotransferase activities using nicotinamide adenine dinucleotide phosphate-linked glutamate dehydrogenase from algae. 255 50

1. The maximum activity of hexokinase in lymphocytes is similar to that of 6-phosphofructokinase, but considerably greater than that of phosphorylase, suggesting that glucose rather than glycogen is the major carbohydrate fuel for these cells. Starvation increased slightly the activities of some of the glycolytic enzymes. A local immunological challenge in vivo (a graft-versus-host reaction) increased the activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and lactate dehydrogenase, confirming the importance of the glycolytic pathway in cell division. 2. The activities of the ketone-body-utilizing enzymes were lower than those of hexokinase or 6-phosphofructokinase, unlike in muscle and brain, and were not affected by starvation. It is suggested that the ketone bodies will not provide a quantitatively important alternative fuel to glucose in lymphocytes. 3. Of the enzymes of the tricarboxylic acid cycle whose activities were measured, that of oxoglutarate dehydrogenase was the lowest, yet its activity (about 4.0mumol/min per g dry wt. at 37 degrees C) was considerably greater than the flux through the cycle (0.5mumol/min per g calculated from oxygen consumption by incubated lymphocytes). The activity was decreased by starvation, but that of citrate synthase was increased by the local immunological challenge in vivo. It is suggested that the rate of the cycle would increase towards the capacity indicated by oxoglutarate dehydrogenase in proliferating lymphocytes. 4. Enzymes possibly involved in the pathway of glutamine oxidation were measured in lymphocytes, which suggests that an aminotransferase reaction(s) (probably aspartate aminotransferase) is important in the conversion of glutamate into oxoglutarate rather than glutamate dehydrogenase, and that the maximum activity of glutaminase is markedly in excess of the rate of glutamine utilization by incubated lymphocytes. The activity of glutaminase is increased by both starvation and the local immunological challenge in vivo. This last finding suggests that metabolism of glutamine via glutaminase is important in proliferating lymphocytes.
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PMID:Maximum activities of some enzymes of glycolysis, the tricarboxylic acid cycle and ketone-body and glutamine utilization pathways in lymphocytes of the rat. 716 29

We describe a serum-inititated aspartate aminotransferase (EC 2.6.1.1) assay that obviates the need for added lactate dehydrogenase (EC 1.1.1.27) in the reagent system. Interference from the oxidation of NADH by endogeneous lactate dehydrogenase is eliminated by adding sodium oxamate, a competitive inhibitor of the enzyme. The advantages of oxamate inhibition over lactate dehydrogenase addition are a shorter preincubation period, an increase in the linear range from less than 600 to more than 1400 U/L, no interference from above-normal concentrations of ketoacids, and elimination of bias between serum-initiated and the standard oxoglutarate-initiated assays for aspartate aminotransferase.
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PMID:Improved serum-initiated aspartate aminotransferase assay by inhibition of lactate dehydrogenase with oxamate. 737 4

We examined the effects of temperature on the activity and steady-state kinetics of aspartate aminotransferase (EC 2.6.1.1), using purified human soluble (s-AspAT) and mitochondrial (m-AspAT) isoenzymes, human serum, and porcine s-AspAT. All enzymes obeyed similar linear Arrhenius relationships over the range 20-40 degrees C. Apparent energies of activation (52.3 kJ.mol-1) and ratios of activity between 30 and 37 degrees C (0.626) were identical for the human s- and m-AspAT. This ratio was 0.623 (SEM 0.004) for human sera; deviation from the predicted ratio by individual sera was within analytical error. Similar activity/temperature relationships were observed for porcine s-AspAT. The use of factors to convert AspAT activities at 30 and 37 degrees C influenced neither precision of measurement of frequency distributions of results. The apparent Michaelis constants for the human isoenzymes increased with temperature. The least-influenced Km was for 2-oxoglutarate and s-AspAT: K2-oxoglutarate was 0.24 mmol.L-1 at 25 degrees C and 0.29 mmol.L-1 at 37 degrees C; apparent enthalpy change for substrate binding (delta HS) was 12.1 kJ.mol-1. The largest variation was for 2-oxoglutarate and m-AspAT: K2-oxoglutarate was 0.46 mmol.L-1 at 25 degrees C and 1.02 mmol.L-1 at 37 degrees C; delta HS was 50.8 kJ.mol-1. Incubation of the human isoenzymes with substrate mixture (without 2-oxoglutarate) at 23 and 37 degrees C did not affect activity during 60 min if tris(hydroxymethyl)aminomethane buffer was used. When the isoenzymes were diluted to 10 nmol-L-1 (about 200 U.L-1) in buffer alone and incubated at 50 degrees C, m-AspAT activity was decreased by 20% after 120 min; the cytoplasmic enzyme was unaffected.
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PMID:Effects of temperature on the steady-state kinetics and measurement of aspartate aminotransferases. 746 Feb 69

The influence of enhancing the supply of hydrogen donors on respiratory rates, NAD(P)H fluorescence, and membrane potential was investigated. Addition of 5 mM malate to mitochondria during oxidation of 10 mM isocitrate, oxoglutarate, succinate, proline, or glycerol-3-phosphate under steady-state conditions resulted in an inhibition of respiration, coincident with a decrease in both transmembrane electrical potential and percentage reduction of NAD(P). Half-maximum inhibition of NAD(P) reduction in the resting state of 10 mM isocitrate respiration was reached at 10 mM malate. This inhibition was concluded to be due to oxaloacetate formed immediately from malate by succinate dehydrogenase. Addition of 5 mM isocitrate caused higher respiratory rates, accompanied by an increase in both delta psi and percentage of NAD(P) reduction, in mitochondria oxidizing 10 mM oxoglutarate, glutamate, proline, hydroxybutyrate, glycerol-3-phosphate, or 0.025 mM palmitoyl carnitine. The half-maximum increase in percentage NAD(P) reduction with 10 mM 2-oxoglutarate as primary substrate was found at 0.24 mM isocitrate. Within the citric acid cycle, succinate dehydrogenase and NAD-isocitrate dehydrogenase play an important role in changes in the rate of NADH formation. Therefore, they participate in flux control. Furthermore, mitochondrial aspartate aminotransferase and oxidoreductases of the beta-oxidation pathway of fatty acids are additionally involved in adjusting the rate of NADH formation.
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PMID:Contribution to control of mitochondrial oxidative phosphorylation by supplement of reducing equivalents. 791 69


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