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 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

A study was performed to determine whether dietary pyridoxine affects the response of rats to arsenic deprivation. A 2 x 2 x 2 factorially arranged experiment utilized groups of 6 male weanling Sprague-Dawley rats. They were fed a 14% amino acid/76% acid-washed corn diet for 10 weeks. The dietary variables were arsenic, 0 or 1 microgram/g; pyridoxine.HCl, 0 or 10 mg/kg, and L-methionine, 0 or 3 g/kg. The basal diet contained 0.24% methionine (calculated) and about 10 ng arsenic/g. Growth was reduced by arsenic, pyridoxine or methionine deprivation. Other parameters including blood indices, erythrocyte aspartate aminotransferase and the concentration of tissue iron and plasma amino acids were affected by dietary arsenic, pyridoxine, methionine or their interaction. The data demonstrate that dietary pyridoxine and arsenic interact and that the methionine status of the animal can affect this interaction.
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PMID:Effect of dietary pyridoxine on arsenic deprivation in rats. 166 17

A study was conducted to investigate morphologic as well as metabolic characteristics of microcarrier-attached hepatocytes in culture, and also to evaluate the effect of intraperitoneal transplantation of the microcarrier-attached hepatocytes on acute hepatic failure in rats induced by D-galactosamine (GalN). Rat hepatocytes were isolated by collagenase perfusion, and cultured on collagen-coated microcarriers. Protein synthesis estimated by [14C] leucine incorporation was four-fold higher in microcarrier culture than in cell suspension. The rates of albumin, transthyretin and bile acid syntheses in hepatocytes cultured on microcarriers were similar to those in monolayer culture. When microcarrier-attached hepatocytes were intraperitoneally transplanted into rats with Galn-induced acute liver failure, a marked improvement in survival rate was observed as compared with control rats which received injections of microcarriers alone (80% vs 0% beyond 6 days of transplantation). Mean serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), methionine and glucose levels were similar in both groups, while serum bilirubin and ammonia levels were lower (P less than 0.1, P less than 0.05) in rats transplanted with the microcarrier-attached hepatocytes. Immunohistochemical examinations revealed that the transplanted hepatocytes around microcarriers had albumin synthesis activity, whereas almost no albumin synthesis was demonstrated in recipient liver. In conclusion, intraperitoneal transplantation of the microcarrier-attached hepatocytes will provide sufficient metabolic support, representing detoxication of ammonia (and presumably bilirubin) and synthesis of albumin, to allow GalN-damaged liver function to restore. Microcarrier culture of isolated hepatocytes seems to be one of the most appropriate tools for an artificial liver support.
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PMID:Effects of intraperitoneal transplantation of microcarrier-attached hepatocytes on D-galactosamine-induced acute liver failure in rats. 168 85

In porcine cytosolic aspartate aminotransferase, a dimeric enzyme, the amino-terminal region anchoring onto the neighboring subunit is linked to the adjoining floppy peptide segment (residues 12-47), an integral part of the small domain whose facile movement upon substrate binding is a striking "induced fit" feature of this enzyme. To assess the contribution by the amino-terminal region to small domain movement and protein stability, a series of enzyme derivatives truncated on the amino-terminal side (residues 1-9) was prepared by using oligonucleotide-directed in vitro mutagenesis. Deletion of residues 1-3 showed no effect on catalytic activity and heat stability. Del 1-5 mutant enzyme with an extra methionine at position 5 showed only 43% of the kappa cat value (in the overall transamination) of the wild-type enzyme. Further deletion up to residue 9 resulted in a slight decrease in kappa cat values. Del 1-9 mutant enzyme still retained a kappa cat value of 33% that of wild-type enzyme. Km values for aspartate and 2-oxoglutarate increased sharply upon deletion of residues 1-9. Accordingly, Del 1-9 mutant enzyme showed a striking decrease in the kappa cat/Km value, to only 2% of that for the wild-type enzyme. Deletion of amino-terminal residues 1-9 resulted also in a large decrease in thermostability and in an enhanced susceptibility to limited proteolysis by protease 401, which is known to cleave at Leu20 of the wild-type enzyme. These findings indicate that an increase in the conformational freedom of the floppy segment (residues 12-47) would occur upon the loss of most of the anchorage region, thereby presenting an entropic barrier to conformational changes that facilitate substrate binding with high affinity.
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PMID:Structural and functional role of the amino-terminal region of porcine cytosolic aspartate aminotransferase. Catalytic and structural properties of enzyme derivatives truncated on the amino-terminal side. 199 12

Two decades of research in ethanol metabolism have culminated in the molecular elucidation of an ethanol-inducible cytochrome P450 (P450IIE1) which is not only involved with ethanol metabolism and ethanol tolerance, but also with the activation of a number of xenobiotics. The unique ability of P450IIE1 to activate xenobiotic agents now appears to be responsible for the increased susceptibility of the heavy drinker to hepatotoxic industrial solvents, commonly used drugs, over-the-counter medications and chemical carcinogens. It also explains some of the interaction of ethanol with nutritional factors, such as hepatic vitamin A: enhanced microsomal degradation of retinoids (together with hepatic mobilisation) promotes depletion. Treatment, however, is complicated by the fact that ethanol also enhances the toxicity of excess vitamin A. All pathways of ethanol metabolism result in the production of acetaldehyde, the toxicity of which has been reviewed (Lieber 1982). New aspects discussed here include the formation of acetaldehyde-protein adducts and an associated immune response that may play a pathogenic role. Also discussed are the implications of ethanol-induced alterations in microtubules, mitochondria and plasma membranes, as they relate, in part, to accompanying acetaldehyde-induced toxicity, to the production of free radicals or to lipid peroxidation-mediated injury associated with glutathione depletion. There is also depletion of S-adenosyl-L-methionine (SAMe). Administration of synthetic SAMe results in a partial correction of the SAMe depletion and a consequent restoration of glutathione levels. Other beneficial effects of SAMe include a significant attenuation of the increase in plasma aspartate transaminase and glutamate dehydrogenase activities. Mitochondrial damage, including giant forms, documented by light and electron microscopy, is also attenuated by SAMe. Thus, the new understanding of the pathophysiology of alcohol-induced liver damage has led to more successful therapy with drugs and nutritional factors.
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PMID:Interaction of alcohol with other drugs and nutrients. Implication for the therapy of alcoholic liver disease. 208 78

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

1. Glutamine was found to be the main carbon and nitrogen product of the metabolism of aspartate in isolated guinea-pig kidney-cortex tubules. Glutamate, ammonia and alanine were only minor products. 2. Carbon-balance calculations and the release of 14CO2 from [U-14C]aspartate indicate that oxidation of the aspartate carbon skeleton occurred. 3. A pathway involving aspartate aminotransferase, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate dehydrogenase and enzymes of the tricarboxylic acid cycle is proposed for the conversion of aspartate into glutamine. 4. Evidence for this pathway was obtained by: (i) inhibiting aspartate removal by amino-oxyacetate, an inhibitor of transaminases, (ii) the use of methionine sulphoximine, an inhibitor of glutamine synthetase, which induced a large increase in ammonia release from aspartate, (iii) the use of quinolinate, an inhibitor of phosphoenolpyruvate carboxykinase, which inhibited glutamine synthesis from aspartate, (iv) the use of alpha-cyano-4-hydroxycinnamate, an inhibitor of the mitochondrial transport of pyruvate, which caused an accumulation of pyruvate from aspartate, and (v) the use of fluoroacetate, an inhibitor of aconitase, which inhibited glutamine synthesis with concomitant accumulation of citrate from aspartate.
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PMID:Glutamine synthesis from aspartate in guinea-pig renal cortex. 236 82

The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on various serum constituents were studied following subcutaneous injection (12.5 or 125 micrograms/kg) in female Wistar rats. Protein electrophoresis and the determination of the serum concentrations of carboxypeptidase N (CPN), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, aldolase, total proteins, iron, urea, creatinine, and several amino acids were performed 12, 24, and 72 hr after injection. With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration. Iron and CPN were still low after 24 hr but returned to normal levels after 72 hr. With the higher dose of rhIL-1 beta, only alanine and phenylalanine levels were increased after 12 and 72 hr, taurine after 12 hr, and methionine after 24 hr. There were no biochemical or histological signs of hepatotoxicity. The findings indicate that rhIL-1 beta produces a reversible alteration of various biochemical plasma constituents without any apparent signs of cytotoxicity. Moreover, the decrease in CPN observed may influence the degradation of inflammatory peptides.
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PMID:Recombinant human interleukin-1 beta decreases serum carboxypeptidase N and modifies serum amino acid concentrations in rats. 278 29

Both the precursor and the mature form of chicken mitochondrial aspartate aminotransferase were synthesized in Escherichia coli. The precursor was found to sediment quantitatively together with insoluble cell material. In contrast, mature mitochondrial aspartate aminotransferase could be readily extracted from the cells and was indistinguishable from the enzyme isolated from chicken heart in all respects tested: specific activity 230 units mg-1; Mr 2 X 45,000; pI greater than 9; NH2-terminal sequence SSWWSHVEMG, the initiator methionine having been removed by the bacteria. Thus, the polypeptide chain representing mature mitochondrial aspartate aminotransferase is an autonomous folding unit which attains its functional spatial structure independently of the presence of the prepiece, trans-membrane passage, and proteolytic processing.
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PMID:Expression of cDNAs encoding the precursor and the mature form of chicken mitochondrial aspartate aminotransferase in Escherichia coli. 330 9

Mitochondrial aspartate aminotransferase is synthesized on free polysomes as a higher molecular weight precursor (Sonderegger, P., Jaussi, R., Christen, P., and Gehring, H. (1982) J. Biol. Chem. 257, 3339-3345). The present study examines whether the coenzyme pyridoxal phosphate or pyridoxamine phosphate is required for the uptake of the precursor into mitochondria. Chicken embryo fibroblasts were cultured in medium prepared with and without pyridoxal. In cells grown in the presence of pyridoxal only holoform of aspartate aminotransferase and no apoenzyme was detected. Cells cultured under pyridoxal deficiency contained about 30% of apoenzyme in secondary cultures. All of this apoform was identified as mitochondrial isoenzyme. In order to differentiate whether this apoenzyme corresponded to newly synthesized protein or originated from pre-existing holoenzyme, double isotope-labeling experiments were performed. Secondary cultures of chicken embryo fibroblasts grown under pyridoxal depletion were labeled with [3H]methionine, and then pulsed with [35S]methionine. In another series of experiments, the 3H-labeled cells were pulsed with [35S]methionine in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone in order to accumulate the precursor. Subsequently, the accumulated precursor was chased into the mitochondria by addition of the carbonyl cyanide m-chlorophenylhydrazone antagonist cysteamine. The holo- and apoenzyme from the ultrasonic extract of the double-labeled cells were separated by affinity chromatography on a phosphopyridoxyl-AH-Sepharose column, immunoprecipitated, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Under both experimental conditions, the 3H/35S ratio of the apoenzyme was less than half of that of the holoenzyme. Therefore, the apoenzyme and not the holoenzyme is the first product of the precursor in the mitochondria. Apparently, the precursor of mitochondrial aspartate aminotransferase is transported into mitochondria as apoprotein and is processed there independently of the coenzyme.
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PMID:The precursor of mitochondrial aspartate aminotransferase is translocated into mitochondria as apoprotein. 373 49


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