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

In previous studies it was found that: (a) aspartate aminotransferase increases the aspartate dehydrogenase activity of glutamate dehydrogenase; (b) the pyridoxamine-P form of this aminotransferase can form an enzyme-enzyme complex with glutamate dehydrogenase; and (c) the pyridoxamine-P form can be dehydrogenated to the pyridoxal-P form by glutamate dehydrogenase. It was therefore concluded (Fahien, L.A., and Smith, S.E. (1974) J. Biol. Chem 249, 2696-2703) that in the aspartate dehydrogenase reaction, aspartate converts the aminotransferase into the pyridoxamine-P form which is then dehydrogenated by glutamate dehydrogenase. The present results support this mechanism and essentially exclude the possibility that aspartate actually reacts with glutamate dehydrogenase and the aminotransferase is an allosteric activator. Indeed, it was found that aspartate is actually an activator of the reaction between glutamate dehydrogenase and the pyridoxamine-P form of the aminotransferase. Aspartate also markedly activated the alanine dehydrogenase reaction catalyzed by glutamate dehydrogenase plus alanine aminotransferase and the ornithine dehydrogenase reaction catalyzed by ornithine aminotransferase plus glutamate dehydrogenase. In these latter two reactions, there is no significant conversion of aspartate to oxalecetate and other compounds tested (including oxalacetate) would not substitute for aspartate. Thus aspartate is apparently bound to glutamate dehydrogenase and this increases the reactivity of this enzyme with the pyridoxamine-P form of aminotransferases. This could be of physiological importance because aspartate enables the aspartate and ornithine dehydrogenase reactions to be catalyzed almost as rapidly by complexes between glutamate dehydrogenase and the appropriate mitochondrial aminotransferase in the absence of alpha-ketoglutarate as they are in the presence of this substrate. Furthermore, in the presence of aspartate, alpha-ketoglutarate can have little or no affect on these reactions. Consequently, in the mitochondria of some organs these reactions could be catalyzed exclusively by enzyme-enzyme complexes even in the presence of alpha-ketoglutarate. Rat liver glutamate dehydrogenase is essentially as active as thebovine liver enzyme with aminotransferases. Since the rat liver enzyme does not polymerize, this unambiguously demonstrates that monomeric forms of glutamate dehydrogenase can react with aminotransferases.
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PMID:Effect of aspartate on complexes between glutamate dehydrogenase and various aminotransferases. 1 47

Individual enzyme-inhibitor complexes with characteristic absorption spectra have been obtained as a result of the reaction of the apoenzyme of aspartate aminotransferase with Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, Nalpha-(5'-phosphopyridoxyl)-D-glutamic acid, and Nalpha-(5'-phosphopyridoxyl)-L-pyroglutamic acid. The stability of the enzyme-inhibitor complexes has been investigated under various conditions, viz., reactivation by the coenzyme, denaturation by urea, variations in the pH. It has been shown that the complexes formed by the last two inhibitors are reactivated by pyridoxal-5'-phosphate and that the inhibitor can be released under mild conditions. The enzyme-inhibitor complex formed by Nalpha-(5'-phosphopyridoxyl)-L-glutamic acid, on the other hand, was not reactivated by the coenzyme. Pyridoxylglutamic acid has been isolate in attempts to release the inhibitor. The dephosphorylation of the inhibitor has been associated both with the hydrolysis of a phosphate bond involving the enzyme and with the phosphorylation of aspartate aminotransferase. A 32P peptide containing 13 amino acids has been isolated from the tryptic hydrolysate of the enzyme-inhibitor complex (formed by a 32P inhibitor). The data obtained have been interpreted on the basis of an assumption that the phosphate group of the coenzyme has an active role in the enzymatic transamination reaction.
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PMID:Labilization of the phosphoester linkage in enzyme-inhibitor complexes of aspartate aminotransferase. 1 13

The selective reaction of Cys-45 and -82, on the one hand, and Cys-390, on the other, with 3-bromo-1,1,1-trifluoropropanone allows for the probing of these regions of aspartate transaminase in the absence and in the presence of enzymatic ligands by 19F nuclear magnetic resonance (NMR). The 19F chemical shifts of the resonance lines differ for the three cysteines and so does their behavior with pH changes. The resonance signals with chemical shifts at 615 and 800 Hz upfield from trifluoroacetic acid correspond to modified cysteine-82 and -45 and have tentatively been assigned in this order. The 615-Hz resonance is affected by pH changes that fit best the influence of a single ionizing residue. On the 800-Hz line, the pH changes appear to be the influence of a minimum of two ionizing residues. The 19F resonance from modified Cys-390 is pH independent in the pH range 5-9 for the pyridoxal phosphate, pyridoxamine phosphate, and apoenzyme forms of the enzyme. Occupation of the active site by a quasi-enzyme-substrate complex, trifluoromethionine pyridoxyl phosphate, affects the 19F chemical shift of modified Cys-390, making it pH dependent with a pK value of 8.4. The 19F NMR properties of the pyridoxal form of Cys-390-modified enzyme can be used to monitor some ligand interactions with the active-center region. Addition of alpha-ketoglutarate or succinate to the ketone labeled enzyme causes a decrease in the resonance line width, and titrations show that this procedure is a good method with which to study the affinity of the enzyme for these ligands. The interpretation of the chemical shift and line-width characteristics of the 19F resonance arising from Cys-390 are most consistent with a model in which the region around this residue seems to be affected by conformational changes arising from substrate binding to the active-center subsites in productive (covalent) manner. Nonproductive complexes which possess fast ligand-protein exchange, such as those between alpha-ketoglutarate or succinate with the pyridoxal phosphate form of the enzyme, may result only in a greater degree of freedom for Cys-390.
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PMID:Fluorine-19 nuclear magnetic resonance studies of effects of ligands on trifluoroacetonylated supernatant aspartate transaminase. 1 84

We report the intermediate-term effects of three consecutive evenings of moderate ethanol ingestion (0.75 g/kg body weight each evening) on activity values for alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in sera of nine apparently healthy young adults. We define "intermediate-term" effects as those occurring between 10 h and 100 h after completion of the ethanol consumption schedule. The most pronounced changes in enzyme activity for the group of volunteers were: gamma-glutamyltransferase, +25% at 60 h after ethanol ingestion; alanine aminotransferase, +12% at 60 h after ethanol; and aspartate aminotransferase,--12% at 60 h after ethanol. All three enzymes exhibited similar time courses, i.e., mean peak activity changes were observed at 60 h, and all three mean enzyme activity values returned to near baseline by 100 h. The possible explanations for the observed changes and the clinical significance are discussed.
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PMID:The effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 1. Intermediate-term effects. 1 40

gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown.
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PMID:Late persistence of serum gamma-glutamyl transpeptidase activity after mononucleosis. Report of 3 cases. 1 21

Two new mutations are described which, together, eliminate essentially all the aminotransferase activity required for de novo biosynthesis of tyrosine, phenylalanine, and aspartic acid in a K-12 strain of Escherichia coli. One mutation, designated tyrB, lies at about 80 min on the E. coli map and inactivates the "tyrosine-repressible" tyrosine/phenylalanine aminotransferase. The second mutation, aspC, maps at about 20 min and inactivates a nonrespressible aspartate aminotransferase that also has activity on the aromatic amino acids. In ilvE- strains, which lack the branched-chain amino acid aminotransferase, the presence of either the tyrosine-repressible aminotransferase or the aspartate aminotransferase is sufficient for growth in the absence of exogenous tyrosine, phenylalanine, or aspartate; the tyrosine-repressible enzyme is also active in leucine biosynthesis. The ilvE gene product alone can reverse a phenylalanine requirement. Biochemical studies on extracts of strains carrying combinations of these aminotransferase mutations confirm the existence of two distinct enzymes with overlapping specificities for the alpha-keto acid analogues of tyrosine, phenylalanine, and aspartate. These enzymes can be distinguished by electrophoretic mobilities, by kinetic parameters using various substrates, and by a difference in tyrosine repressibility. In extracts of an ilvE- tyrB- aspC- triple mutant, no aminotransferase activity for the alpha-keto acids of tyrosine, phenylalanine, or aspartate could be detected.
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PMID:Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases. 1 83

To assess potential toxic effects liver biopsies were performed before and after 6-8 months therapy with chenodeoxycholic acid (CDCA), 750 mg daily, in 6 patients with gallbladder stones. Minor fatty change and lipofuscin were seen prior to therapy, which tended to increase afterwards. Otherwise there was no consistent change on light microscopy. Electron microscopy showed parallel changes in the hepatocytes with no marked damage. There was a patchy loss of microvilli in the biliary epithelium. However, there was a significant increase in sinusoidal lipocytes or Ito cells, which was seen in every case. These 6 patients were representative of a group of 20 patients in whom serum liver function tests have been followed monthly for at least 6 months. During this period aspartate aminotransferase levels rose slightly but significantly, the mean remaining within the normal range. There was a trend to a decline in alpha-glutamyl transpeptidase levels, but this was less impressive and not statistically significant.
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PMID:Effect of gallstone-dissolution therapy on human liver structure. 1 80

Comparative biochemical studies on phosphorylase b, aspartate aminotransferase and alanine aminotransferase in muscles of various vertebrates (the lamprey Lampetra fluviatilis, dogfish Squalus acanthias, rays Dasyatis pastinaca and Raja clavata, teleosts Scorpaena porcus, Spicara smaris, Esox lucius, Tinca tinca, Abramis brama, Lucioperca lucioperca, Cyprinus carpio, Salmo ischchan, frog Rana temporaria, tortoise Testudo horsfieldi) revealed some peculiarties of their molecular evolution. It was shown that isoenzyme PH-II, which comprises in most on the investigated lower vertebrates the main bulk of phosphorylase b, disappears in evolution of the type. Isoenzyme PH-I which is found in fisches in small amounts, increases in evolution becoming the sole form of phosphorylase b in skeletal muscles of endothermic animals. Mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase were found in all the vertebrates studied. Cytoplasmic isoenzyme from ectothermic and endothermic animals does not differ significantly, whereas the mitochondrial one undergoes considerable changes in the evolution of vertebrates.
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PMID:[Molecular evolution of glycogen phosphorylase and aminotransferases of vertebrate muscle tissue]. 1 51

Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor.
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PMID:[19F]fluorine nuclear-magnetic-resonance study of the interaction of difluoro-oxaloacetate with aspartate transaminase. 1 99

A spectrophotometric assay has been developed for the determination of the content of each isozyme of aspartate transaminase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) in physiological fluids or tissue extracts. The methods relies on the ability of adipate, at low pH and ionic strength to inhibit the cytoplasmic isozyme but not the one from mitochondria. Two assays are necessary, one at pH 8.0 which measures the content of both isozymes and another at low pH which measures primarily the amount of mitochondrial isozyme. Results obtained by this simple procedure match those in which each isozyme is inhibited by its antibody. The validity of the results obtained by the new method was tested at different ratios of cytoplasmic:mitochondrial isozyme and with tissue extracts. Since the amounts of each isozyme determined by radial immunodiffusion match those values gathered by following enzymatic activity, it is concluded that the quantity of each isozyme obtained from its respective catalytic activity must represent the total protein content of each isozyme in a given sample.
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PMID:On the determination of isozyme levels in preparations containing cytoplasmic and mitochondrial aspartate aminotransferase. 1 83


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