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)

Transaminase B (branched-chain amino acid aminotransferase, EC 2.6.1.42), the ilvE gene product, was purified to apparent homogeneity from an Escherichia coli K-12 strain which carries the ilvE gene both on the host chromosome and on a plasmid. The oligomeric structure of the enzyme, as determined by analytical ultracentrifugation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was confirmed to be that of a hexamer with a molecular weight of about 182,000 and apparently identical subunits. Cross-linking with dimethylsuberimidate yielded trimers, dimers, and monomers, but essentially no species of higher molecular weight. These results are consistent with a double-trimer arrangement of the subunits in native enzyme. The amino-terminal sequence was found to be: Gly Thr Lys Lys Ala Asp Tyr Ile (Trp) Phe Asn Gly (Thr) (Met) Val. Purified transaminase B catalyzed transamination between alpha-ketoglutarate and l-isoleucine, l-leucine, l-valine, and, to a lesser extent, l-phenylalanine and l-tyrosine, the latter reacting very sluggishly. The enzyme was free of aspartate transaminase and of transaminase C. The apparent K(m) values for the branched-chain alpha-ketoacids were smaller than those for the corresponding amino acids. The lowest K(m) was recorded for dl-alpha-keto-beta-methyl-n-valerate, and the highest was recorded for l-valine. The ratio of the valine- and isoleucine-alpha-ketoglutarate activities did not change significantly during purification, and both activities were quantitatively removed from crude extract by antibody raised against purified transaminase B. These observations argue against the existence of a separate valine-alpha-ketoglutarate transaminase. Anti-E. coli transaminase B antibody cross-reacted with crude extract from Salmonella typhimurium, but not with extract obtained from Pseudomonas aeruginosa.
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PMID:Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity. 37 64

The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis.
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PMID:Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat. 159 Jun 69

Four aminotransferases were identified and characterized from Methanococcus aeolicus. Branched-chain aminotransferase (BcAT, EC 2.6.1.42), aspartate aminotransferase (AspAT, EC 2.6.1.1), and two aromatic aminotransferases (EC 2.6.1.57) were partially purified 175-, 84-, 600-, and 30-fold, respectively. The apparent molecular weight, substrate specificity, and kinetic properties of the BcAT were similar to those of other microbial BcATs. The AspAT had an apparent molecular weight of 162,000, which was unusually high. It had also a broad substrate specificity, which included activity towards alanine, a property which resembled the enzyme from Sulfolobus solfataricus. An additional alanine aminotransferase was not found in M. aeolicus, and this activity of AspAT could be physiologically significant. The apparent molecular weights of the aromatic aminotransferases (ArAT-I and ArAT-II) were 150,000 and 90,000, respectively. The methanococcal ArATs also had different pIs and kinetic constants. ArAT-I may be the major ArAT in methanococci. High concentrations of 2-ketoglutarate strongly inhibited valine, isoleucine, and alanine transaminations but were less inhibitory for leucine and aspartate transaminations. Aromatic amino acid transaminations were not inhibited by 2-ketoglutarate. 2-Ketoglutarate may play an important role in the regulation of amino acid biosynthesis in methanococci.
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PMID:Characterization of amino acid aminotransferases of Methanococcus aeolicus. 172 42

Twenty-four hours after acute administration of cocaine HCl (25 mg/kg, i.p.) to male C57BL/6ByJ mice, there was no hepatotoxicity as measured by plasma aspartate aminotransferase (AST) activity. In contrast, daily administration of cocaine (25 mg/kg, i.p.) for 14 days induced marked hepatotoxicity, as characterized by a greater than 400% increase in plasma AST activity when assayed 24 hr after the last injection. Concomitantly, the liver had increased levels of cysteine, gamma-glutamylcysteine, glutathione, cysteinylglycine, glutamate, methionine, taurine, and aspartate. The effect appeared to be selective for compounds of the glutathione metabolic pathways, because repeated cocaine exposure did not affect other amino acids such as leucine, isoleucine, phenylalanine, serine, and valine. There was a positive correlation between the magnitude of the elevation of cysteine and the extent of liver damage. Daily cocaine administration did not affect striatal or frontal cortex glutathione. A final cocaine challenge (50 mg/kg, i.p.) did not affect either hepatic or cerebral glutathione metabolism. The increase in hepatic cysteine and glutathione upon daily cocaine administration is a potentially important compensatory mechanism against cocaine-induced hepatotoxicity.
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PMID:Differential effects of daily administration of cocaine on hepatic and cerebral glutathione in mice. 224 12

Arg292 of E. coli aspartate aminotransferase was substituted with valine or leucine by site-directed mutagenesis. In comparison with the wild-type enzyme, either of the mutant enzymes showed a decrease by over 5 orders of magnitude of kcat/km values for aspartate and glutamate. This supports the contention that Arg292 is important for determining the specificity of this enzyme for dicarboxylic substrates. In contrast, mutant enzymes displayed a 5- to 10-fold increase in kcat/Km values for aromatic amino acids as substrates. Thus, introduction of an uncharged, hydrophobic side chain into position 292 leads to a striking alteration in substrate specificity of this enzyme, thereby improving catalytic efficiency toward aromatic amino acids.
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PMID:[Arg292----Val] or [Arg292----Leu] mutation enhances the reactivity of Escherichia coli aspartate aminotransferase with aromatic amino acids. 256 74

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
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PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18

Muscle branched-chain amino acid metabolism is coupled to alanine formation via branched-chain amino acid aminotransferase and alanine aminotransferase, but the subcellular distributions of these and other associated enzymes are uncertain. Recovery of branched-chain aminotransferase in the cytosol fraction after differential centrifugation was shown to be accompanied by leakage of mitochondrial-matrix marker enzymes. By using a differential fractional extraction procedure, most of the branched-chain aminotransferase activity in rat muscle was located in the mitochondrial compartment, whereas alanine aminotransferase was predominantly in the cytosolic compartment. Phosphoenolpyruvate carboxykinase, like aspartate aminotransferase, was approximately equally distributed between these subcellular compartments. This arrangement necessitates a transfer of branched-chain amino nitrogen and carbon from the mitochondria to the cytosol for alanine synthesis de novo to occur. In incubations of hemidiaphragms from 48 h-starved rats with 3mM-valine or 3mM-glutamate, the stimulation of alanine release was inhibited by 69% by 1 mM-aminomethoxybut-3-enoate, a selective inhibitor of aspartate aminotransferase. Leucine-stimulated alanine release was unaffected. These data implicate aspartate aminotransferase in the transfer of amino acid carbon and nitrogen from the mitochondria to the cytosol, and suggest that oxaloacetate, via phosphoenolpyruvate carboxykinase, can serve as an intermediate on the route of pyruvate formation for muscle alanine synthesis.
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PMID:Branched-chain amino acid metabolism and alanine formation in rat muscles in vitro. Mitochondrial-cytosolic interrelationships. 397 57

The chemical and spectroscopic properties of 6-fluoropyridoxal 5'-phosphate, of its Schiff base with valine, and of 6-fluoropyridoxamine 5'-phosphate have been investigated. The modified coenzymes have also been combined with the apo form of cytosolic aspartate aminotransferase, and the properties of the resulting enzymes and of their complexes with substrates and inhibitors have been recorded. Although the presence of the 6-fluoro substituent reduces the basicity of the ring nitrogen over 10 000-fold, the modified coenzymes bind predominately in their dipolar ionic ring forms as do the natural coenzymes. Enzyme containing the modified coenzymes binds substrates and dicarboxylate inhibitors normally and has about 42% of the catalytic activity of the native enzyme. The fluorine nucleus provides a convenient NMR probe that is sensitive to changes in the state of protonation of both the ring nitrogen and the imine or the -OH group of free enzyme and of complexes with substrates or inhibitors. The NMR measurements show that the ring nitrogen of bound 6-fluoropyridoxamine phosphate is protonated at pH 7 or below but becomes deprotonated at high pH around a pKa of 8.2. The bound 6-fluoropyridoxal phosphate, which exists as a Schiff base with a dipolar ionic ring at high pH, becomes protonated with a pKa of approximately 7.1, corresponding to the pKa of approximately 6.4 in the native enzyme. Below this pKa a single 19F resonance is seen, but there are two light absorption bands corresponding to ketoenamine and enolimine tautomers of the Schiff base. The tautomeric ratio is altered markedly upon binding of dicarboxylate inhibitors. From the chemical shift values, we conclude that during the rapid tautomerization a proton is synchronously moved from the ring nitrogen (in the ketoenamine) onto the aspartate-222 carboxylate (in the enolimine). The possible implications for catalysis are discussed.
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PMID:Studies of 6-fluoropyridoxal and 6-fluoropyridoxamine 5'-phosphates in cytosolic aspartate aminotransferase. 409 32

Of 33 components analyzed in overnight fasting serum from 30 patients with alcoholic liver cirrhosis, portal hypertension, and bleeding esophageal varices, total serum bile acids, gamma-glutamyltransferase, prealbumin, and tyrosine were the most frequently abnormal 'liver tests'. Total serum bile acids correlated significantly with bilirubin, immunoglobulin M, threonine, glycine, methionine, and tyrosine. Gamma-glutamyltransferase correlated with aspartate aminotransferase, glutamine, and alanine. Prealbumin correlated with albumin and immunoglobulins G and A. Tyrosine correlated with total bile acids, orosomucoid, and 10 amino acids. The amino acid ratio of valine + isoleucine + leucine to tyrosine + phenylalanine was lowered in all patients. It is concluded that the clinical picture and pattern of serum components in patients with alcoholic liver disease are influenced by many complex pathophysiological mechanisms.
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PMID:Total serum bile acids, gamma-glutamyl transferase, prealbumin, and tyrosine: sensitive serum markers of hepatic dysfunction in alcoholic liver cirrhosis. 614 23

L-Leucine and its nonmetabolized analogue, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH) activate glutamate dehydrogenase in pancreatic islets, whether the reaction velocity is measured in the direction of glutamate synthesis or glutamate deamination. The rate of glutamate oxidative deamination is increased by ADP and inhibited by 2-ketoglutarate, NH4+ and GTP. The islet homogenate catalyzes the transamination between L-glutamate and either 2-ketoisocaproate or pyruvate, and between 2-ketoglutarate and L-leucine, L-aspartate, L-alanine, L-isoleucine, L-valine, L-norvaline or L-norleucine, but not b (+/-) BCH. The glutamate-aspartate transaminase is preferentially located in mitochondria relative to other transaminases. The parallel effects of L-leucine and BCH on glutamate dehydrogenase and their vastly different abilities to act as transamination partners may account for both analogies and discrepancies in the metabolic and functional responses of the islets to these two branched-chain amino acids.
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PMID:The stimulus-secretion coupling of amino acid-induced insulin release. XI. Kinetics of deamination and transamination reactions. 675 75


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