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)

Sera of 260 patients with high serum aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1; AST)/alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2; ALT) ratio (greater than 2.0) and high serum AST (greater than 45 IU/1) were selected and tested for the presence of immunoglobulin complexed-AST, by using immunoprecipitation reaction and counterimmunoelectrophoresis. The macromolecular AST was confirmed by size-exclusion high-performance liquid chromatography (HPLC). 34 patients out of 260 were found to have AST-immunoglobulin complexes (13.1%). The classes of AST-linked immunoglobulins were identified to be alpha in 28 cases (82.4%, P less than 0.01), mixed type of alpha and gamma in 5 cases (14.7%) gamma in one case (2.9%). Positive frequency was the highest in liver malignancies, either primary (9/26, 34.6%) or metastatic (7/17, 42.2%), followed by other malignancies (6/55, 10.9%) and chronic liver diseases (4/22, 18.2%). Thus, it can be strongly suggested that the immunoglobulin A complexed-AST is frequently found in association with liver malignancies.
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PMID:Incidence and properties of aspartate aminotransferase-immunoglobulin complexes in patients with a high serum aspartate to alanine aminotransferase ratio. 220 38

This investigation presents disturbances of the mitochondrial metabolism by arsenite, a hydrophilic dithiol reagent known as an inhibitor of mitochondrial alpha-keto acid dehydrogenases. Arsenite at concentrations of 0.1-1.0 mM was shown to induce a considerable oxidation of intramitochondrial NADPH, NADH, and glutathione without decreasing the mitochondrial membrane potential. The oxidation of NAD(P)H required the presence of phosphate and was sensitive to ruthenium red, but occurred without the addition of calcium salts. Mitochondrial reactions producing alpha-ketoglutarate from glutamate and isocitrate were modulated by arsenite through various mechanisms: (i) both glutamate transaminations, with oxaloacetate and with pyruvate, were inhibited by accumulating alpha-ketoglutarate; however, at low concentrations of alpha-ketoglutarate the aspartate aminotransferase reaction was stimulated due to the increase of NAD+ content; (ii) the oxidation of isocitrate was stimulated at its low concentration only, due to the oxidation of NADPH and NADH; this oxidation was prevented by concentrations of citrate or isocitrate greater than 1 mM; (iii) the conversion of isocitrate to citrate was suppressed, presumably as a result of the decrease of Mg2+ concentration in mitochondria. Thus the depletion of mitochondrial vicinal thiol groups in hydrophilic domains disturbs the mitochondrial metabolism not only by the inhibition of alpha-keto acid dehydrogenases but also by the oxidation of NAD(P)H and, possibly, by the change in the ion concentrations.
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PMID:A complex effect of arsenite on the formation of alpha-ketoglutarate in rat liver mitochondria. 227 50

The aromatic amino acid aminotransferase was purified to a homogenous state from a gramicidin S-producing strain of Bacillus brevis. The enzyme shows a molecular weight of about 71,000 on gel-filtration. The subunit molecular weight is about 35,000 as determined by sodium dodecyl sulfate gel electrophoresis, indicating that the enzyme is a dimer. The enzyme exhibits absorption maxima near 425 and 330 nm at neutral pH. One mole of pyridoxal phosphate is bound per subunit. The enzyme has amino donor specificity for aromatic amino acids, L-phenylalanine, L-tyrosine, and L-tryptophan, and utilizes 2-oxoglutarate as the amino acceptor. This enzyme activity was separated from both the aspartate aminotransferase activity and the branched chain amino acid aminotransferase activity by chromatography on DEAE-Sephadex.
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PMID:Purification and properties of the aromatic amino acid aminotransferase from gramicidin S-producing Bacillus brevis. 244 Aug 56

Substitution of a lysyl residue for Arg-386 of Escherichia coli aspartate aminotransferase resulted in an extensive decrease in Vmax values (0.8% with the aspartate-2-oxoglutarate pair and 0.2% with the glutamate-oxalacetate pair, compared with the corresponding values for the wild-type enzyme). Kinetic analysis of the four sets of half-reactions, the pyridoxal form of the enzyme with aspartate or glutamate and the pyridoxamine form with 2-oxoglutarate or oxalacetate, allowed us to define the independent effect of the mutation on the reactivity of each substrate. Decrease in the first order rate constant (kmax) was more pronounced in the reactions with five-carbon substrates (glutamate and 2-oxoglutarate) than in those with four-carbon substrates (aspartate and oxalacetate), while the increase in the apparent dissociation constant (Kd) was greater for four-carbon substrates than for five-carbon substrates. The decrease of overall catalytic efficiency as judged by the values, kmax/Kd, was more pronounced in the reactions with five-carbon substrates than in those with four-carbon substrates. Affinities for substrate analogs such as succinate, glutarate, 2-methylaspartate, and erythro-3-hydroxyaspartate, were also considerably decreased by the mutation of the enzyme. These findings indicate that the side chain of the lysyl residue, although it bears a positive charge similar to that of the arginyl residue, is not structurally adequate for the productive binding of a substrate during catalysis.
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PMID:Substitution of a lysyl residue for arginine 386 of Escherichia coli aspartate aminotransferase. 249 35

The inhibitive effects of chloride anion on the activity of mitochondrial aspartate aminotransferase (L-aspartate: 2-oxoglutarate-aminotransferase EC. 2.6.1.1.) from chicken (Gallus domesticus) and turkey (Maleagris gallopavo) were studied. Steady-state velocities were obtained from a wide range of chloride concentrations. The data were fitted by rational functions of 0:2 and 1:2 for chloride, using a non-linear regression program which guaranteed the fit. The goodness of fit was improved by the use of a computer program that combined model discrimination, parameter refinement and sequential design. It was concluded that chloride aspartate aminotransferase inhibition requires a minimum velocity equation of 1:2 with regard to chloride, and a plausible kinetic mechanism for this experimental result was proposed.
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PMID:Kinetic studies of chloride inhibition in aspartate aminotransferase activity. 250 47

The effects of aminooxyacetic acid (AOAA), a transaminase inhibitor, and 2-oxoglutarate, a precursor to glutamate by the activity of aspartate aminotransferase (AAT), on slices of rat medulla oblongata, cerebellum, cerebral cortex, and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2+-dependent stimulus-evoked release of endogenous glutamate, gamma-aminobutyric acid (GABA), and beta-alanine in all regions examined. AOAA (10(-4) and 10(-3) M) decreased the release of glutamate in the medulla oblongata and cerebellum but not in the hippocampus. L-Canaline, a specific inhibitor of ornithine aminotransferase, did not affect the glutamate release in the medulla. 2-Oxoglutarate (10(-3) M) increased the release of glutamate in the medulla oblongata and cerebellum but not in the cerebral cortex and hippocampus. Treatment with AOAA (10(-4) M) almost abolished the activities of AAT in all regions studied. AOAA (10(-4) and 10(-3) M) increased the stimulus-evoked release of GABA in the cerebellum, cerebral cortex, and hippocampus, whereas the stimulus-evoked release of beta-alanine was decreased by this agent in all regions studied. These results suggest the participation of AAT in the synthesis of the transmitter glutamate in the medulla oblongata and cerebellum of the rat.
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PMID:Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata: effect of aminooxyacetic acid and 2-oxoglutarate. 256 22

The interrelation of palmitate oxidation with amino acid formation in rat brain mitochondria has been investigated in purified mitochondria of nonsynaptic origin by measuring the formation of aspartate, alpha-ketoglutarate, and glutamate during palmitate oxidation, and also by assaying 14C-products of [1-14C]palmitate oxidation. Oxidation of palmitate (or [1-14C]palmitate) resulted in the formation of aspartate (or 14C-aspartate), and the oxidation was inhibited by aminooxyacetate (an inhibitor of transaminase). Palmitate oxidation also resulted in alpha-ketoglutarate formation, which was sensitive to the effect of aminooxyacetate. Addition of NH4Cl was found to increase 14C-products and formation of alpha-ketoglutarate, whereas glutamate formation was not increased unless the rate of palmitate oxidation was reduced by 50% by aminooxyacetate or alpha-ketoglutarate was added exogenously. Exogenous alpha-ketoglutarate was found to decrease 14C-products, but not aspartate formation. These results indicated that palmitate oxidation was closely related to aspartate formation via aspartate aminotransferase. During palmitate oxidation without aminooxyacetate or added alpha-ketoglutarate, however, alpha-ketoglutarate was not available for glutamate formation via glutamate dehydrogenase. We discuss the possibility that this was because (a) oxidative decarboxylation of alpha-ketoglutarate to form succinyl-CoA was favored over glutamate formation for the competition for alpha-ketoglutarate in the same pool, and (b) the pool of alpha-ketoglutarate produced in the aspartate aminotransferase reaction did not serve as substrate for glutamate formation.
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PMID:Study of amino acid formation during palmitate oxidation in rat brain mitochondria. 256 41

Partitioning of the ketimine (or ketimine + quinonoid) intermediate(s) in the mitochondrial aspartate aminotransferase reactions was investigated by following the rates of loss of 18O from carbonyl-18O-enriched alpha-ketoglutarate together with the rate of L-glutamate formation. The ratio of these rate constants was found to equal 1 at 10 degrees C, implying that the above intermediate(s) face(s) equal barriers with respect to the forward and reverse reactions. This partition ratio of 1 together with that measured from the alpha-amino acid side of the reaction [Julin, D.A., Wiesinger, H., Toney, M. D., & Kirsch, J.F. (1989) Biochemistry (preceding paper in this issue)] suggests that the rate constant for exchange of alpha-ketoglutarate-derived H2(18)O from the ketimine (or ketimine + quinonoid) form(s) of the enzyme with solvent is comparable with that for kcat.
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PMID:Aspartate aminotransferase catalyzed oxygen exchange with solvent from oxygen-18-enriched alpha-ketoglutarate: evidence for slow exchange of enzyme-bound water. 256 51

Pathways of glutamine metabolism in resting and proliferating rat thymocytes and established human T- and B-lymphoblastoid cell lines were evaluated by in vitro incubations of freshly prepared or cultured cells for one to two hours 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. Similar results were obtained with the lymphoblastoid T- and B-cell lines. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for only 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 lymphocytes appears to be transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as a 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:Metabolism of glutamine in lymphocytes. 256 63

Evoked release of glutamate and aspartate from cultured cerebellar granule cells was studied after preincubation of the cells in tissue culture medium with glucose (6.5 mM), glutamine (1.0 mM), D[3H] aspartate and in some cases aminooxyacetate (5.0 mM) or phenylsuccinate (5.0 mM). The release of endogenous amino acids and of D-[3H] aspartate was measured under physiological and depolarizing (56 mM KCl) conditions both in the presence and absence of calcium (1.0 mM), glutamine (1.0 mM), aminooxyacetate (5.0 mM) and phenylsuccinate (5.0 mM). The cellular content of glutamate and aspartate was also determined. Of the endogenous amino acids only glutamate was released in a transmitter fashion and newly synthesized glutamate was released preferentially to exogenously supplied D-[3H] aspartate, a marker for exogenous glutamate. Evoked release of endogenous glutamate was reduced or completely abolished by respectively, aminooxyacetate and phenylsuccinate. In contrast, the release of D-[3H] aspartate was increased reflecting an unaffected release of exogenous glutamate and an increased "psuedospecific radioactivity" of the glutamate transmitter pool. Since aminooxyacetate and phenylsuccinate inhibit respectively aspartate aminotransferase and mitochondrial keto-dicarboxylic acid transport it is concluded that replenishment of the glutamate transmitter pool from glutamine, formed in the mitochondrial compartment by the action of glutaminase requires the simultaneous operation of mitochondrial keto-dicarboxylic acid transport and aspartate aminotransferase which is localized both intra- and extra-mitochondrially. The purpose of the latter enzyme apparently is to catalyze both intra- and extra-mitochondrial transamination of alpha-ketoglutarate which is formed intramitochondrially from the glutamate carbon skeleton and transferred across the mitochondrial membrane to the cytosol where transmitter glutamate is formed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of aspartate aminotransferase and mitochondrial dicarboxylate transport for release of endogenously and exogenously supplied neurotransmitter in glutamatergic neurons. 256 74


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