Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homogeneous aspartate aminotransferase (purity--99%, yield--70%) has been prepared from chicken heart cytosol. The purification procedure included fractionation with ammonium sulfate and ethanol and crystallization. Crystals (0.3 x 0.5 x 2 mm) of the free enzyme were prepared from ammonium sulfate solution and studied by X-ray analysis at 2.5 A resolution.
 ...
PMID:[Crystallization of free aspartate aminotransferase from chicken heart cytosol]. 178 67

This study was concerned with the role of Cu and Cu-MT (metallothionein) in oxidative stress. Because hepatic Cu and Cu-MT concentrations are known to be high in the 3-day-old guinea pigs but decline to low adult levels by 7 days of life, the hepatotoxicity of ferric nitrilotriacetate (FeNTA) in the developing guinea pig was used as the experimental model in the present study. Results of this study showed that the hepatotoxic response to FeNTA (3.5 mg Fe /kg i.p.) as measured by elevation in serum aspartate aminotransferase activity, increase in lipid peroxidation, decrease in reduced glutathione/oxidized glutathione ratio and histopathological changes was higher in 3-day-old than in 7-day-old and adult guinea pigs. Furthermore, pretreatment of 7-day-old guinea pigs with cupric sulfate (0.5 mg Cu++/kg i.p.) increased hepatic Cu and Cu-MT levels and enhanced susceptibility to FeNTA. FeNTA treatment resulted in the oxidation of MT thiolates and reduction in the metal binding capacity and Cu content of MT in the 3-day-old and Cu-pretreated 7-day-old animals, providing evidence for the interaction between Cu-MT and cellular oxidants. In vitro study with FeNTA and hepatic microsomes revealed no age-related differences in microsomal lipid peroxidation; however, this parameter was stimulated in the presence of control or heat-treated cytosols isolated from 3-day-old but not those of 7-day-old animals. These observations were consistent with the involvement of Cu-MT, a heat-stable metalloprotein, in the sensitization of hepatic tissues to oxidative injury in the 3-day-old animal. Moreover, in vitro study involving the use of D-penicillamine, a Cu chelating agent, showed that the sensitization effect of Cu-MT was mediated by Cu ions. The results of this study suggest that Cu-MT may have a prooxidative property and tissues with high Cu-MT levels may be particularly susceptible to oxidative stress.
 ...
PMID:Age-related differences in iron-nitrilotriacetate hepatotoxicity in the guinea pig: role of copper metallothionein. 189 Jun 21

Acetaminophen (APAP)-induced cytotoxicity and metabolism were studied in hepatocyte cultures isolated from the rat, rabbit, dog, and monkey. Cytotoxicity was evaluated by morphological examination and by alanine aminotransferase and aspartate aminotransferase released into the cell culture medium. The toxicity results obtained by these two methods were in agreement and can be explained by the biotransformation of APAP in each species. Rat and dog hepatocyte cultures contained the most APAP-sulfate conjugates, while the rabbit, dog, and monkey hepatocyte cultures contained the most APAP-glucuronide conjugates. The percentage of APAP-glutathione conjugate was very low in all species, indicating that either very little of the toxic APAP metabolite, N-acetylbenzoquinoneimine, was formed, or in the species susceptible to N-acetylbenzoquinoneimine-induced cytotoxicity, the glutathione S-transferase activity or the amount of glutathione was low. Rabbit hepatocytes transformed the most APAP during both short and long periods of exposure. Of the four species, the dog hepatocytes exhibited the highest level of APAP-induced cytotoxicity. The sensitivity of dog hepatocytes to APAP may be due to their low conjugating enzyme activity. Rat hepatocytes utilized all three pathways of APAP-biotransformation to prevent APAP-induced cytotoxicity. Monkey hepatocyte cultures had a very large capacity to transform APAP to a glucuronide conjugate and a very high level of glutathione S-transferase activity, and therefore did not exhibit any cytotoxicity. These studies indicate that the competing pathways of APAP conjugation in hepatocyte cultures from different species explain the differences observed in APAP-induced cytotoxicity.
 ...
PMID:Metabolism and cytotoxicity of acetaminophen in hepatocyte cultures from rat, rabbit, dog, and monkey. 198 16

The gene encoding aspartate aminotransferase of a thermophilic Bacillus species, YM-2, has been cloned and expressed efficiently in Escherichia coli. The primary structure of the enzyme was deduced from nucleotide sequences of the gene and confirmed mostly by amino acid sequences of tryptic peptides. The gene consists of 1,176 base pairs encoding a protein of 392 amino acid residues; the molecular mass of the enzyme subunit is estimated to be 42,661 daltons. The active site lysyl residue that binds the coenzyme, pyridoxal phosphate, was identified as Lys-239. Comparison of the amino acid sequence with those of aspartate aminotransferases from other organisms revealed very low overall similarities (13-14%) except for the sequence of the extremely thermostable enzyme from Sulfolobus solfataricus (34%). Several amino acid residues conserved in all the compared sequences include those that have been reported to participate in binding of the coenzyme in three-dimensional structures of the vertebrate and E. coli enzymes. However, the strictly conserved arginyl residue that is essential for binding of the distal carboxyl group of substrates is not found in the corresponding region of the sequences of the thermostable enzymes from the Bacillus species and S. solfataricus. The Bacillus aspartate aminotransferase has been purified from the E. coli clone cell extracts on a large scale and crystallized in the buffered ammonium sulfate solution by the hanging drop method. The crystals are monoclinic with unit cell dimensions a = 121.2 A, b = 110.5 A, c = 81.8 A, and beta = 97.6 degrees, belonging to space group C2, and contain two molecules in the asymmetric unit. The crystals of the enzyme-alpha-methylaspartate complex are isomorphous with those without the substrate analog.
 ...
PMID:Thermostable aspartate aminotransferase from a thermophilic Bacillus species. Gene cloning, sequence determination, and preliminary x-ray characterization. 199 6

Both cysteinesulfinate-independent and cysteinesulfinate-dependent pathways are involved in the catabolism of cyst(e)ine by freshly isolated rat renal cortical tubules. Sulfate and thiosulfate were shown to be the major sulfur-containing products that accumulated in incubations of renal tubules with 1 mmol/L or 25 mmol/L [35S]cyst(e)ine. Thiosulfate is an intermediate in the oxidation of the sulfide produced by the cysteinesulfinate-independent catabolism of cyst(e)ine by desulfhydration pathway(s), whereas sulfate is formed both by further oxidation of thiosulfate and by oxidation of the sulfite formed by the cysteinesulfinate-transamination pathway. Incubation of renal tubules with propargylglycine inhibited gamma-cystathionase activity by 85%, and this resulted in a 46% decrease in sulfate production and a 68% decrease in thiosulfate production when the treated renal tubules were incubated with 1 mmol/L [35S]cyst(e)ine. Addition of 25 mmol/L unlabeled cysteinesulfinate to create a diluting/trapping pool for [35S]cysteinesulfinate formed from [35S]cysteine resulted in a 53% decrease in [35S]sulfate production in incubations with 1 mmol/L cysteine. Thus, some cyst(e)ine catabolism probably occurred by a cysteinesulfinate-dependent pathway. No production of taurine or hypotaurine was detected in incubations with cyst(e)ine. Thus, cysteinesulfinate formed from cysteine was further catabolized primarily to sulfate instead of to taurine and hypotaurine. Most cyst(e)ine catabolism by the epithelial cells of the renal tubule probably can be accounted for by two pathways: 1) the beta-cleavage of cystine catalyzed by lambda-cystathionase and 2) the formation and transamination of cysteinesulfinate catalyzed by cysteine dioxygenase and aspartate aminotransferase.
 ...
PMID:Catabolism of cyst(e)ine by rat renal cortical tubules. 211 78

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.
 ...
PMID:Purification and properties of the aromatic amino acid aminotransferase from gramicidin S-producing Bacillus brevis. 244 Aug 56

The autonomic mechanisms of fasting-induced bradycardia of cattle were studied using heart rate spectral analysis. This was performed on digitized, lead II, surface electrocardiograms from conscious, fed, and 48-h-fasted adult cows. Fasting resulted in a significant (P less than 0.05) decrease in resting heart rate and a significant (P = 0.0041) increase in low frequency (0-90 mHz) power spectral area. Administration of atropine sulfate (0.02 mg/kg iv) in either the fed or fasted state resulted in a significant (P less than 0.001) decrease in both low-frequency and high-frequency (100-400 mHz) power spectral areas. Significant (P less than 0.05) increases in serum total bilirubin, inorganic phosphorus, and total protein were associated with fasting. Significant decreases were seen in fasting serum aspartate aminotransferase and potassium values. Manual evacuation of the rumen of seven steers with chronic rumen fistulae resulted in a mean percent decrease in heart rate of 22 +/- 0.9% (mean +/- SE). These results indicate that in normal cattle a decrease in ruminorecticular fill results in a reflex slowing of the heart rate, due predominantly to an increase in parasympathetic tone.
 ...
PMID:Heart rate spectral analysis of fasting-induced bradycardia of cattle. 260 92

The precursor to rat liver mitochondrial aspartate aminotransferase has been expressed in Escherichia coli JM105 using the pKK233-2 expression vector. This mammalian natural precursor has been isolated as a soluble dimeric protein. The amino-terminal sequence and the amino acid composition of the isolated protein correspond to those predicted from the inserted cDNA (Mattingly, J. R., Jr., Rodriguez-Berrocal, F. J., Gordon, J., Iriarte, A., and Martinez-Carrion, M. (1987) Biochem. Biophys. Res. Commun. 149, 859-865). The isolated precursor contains bound pyridoxal phosphate and shows catalytic activity with a specific activity equal to that of the mature form of the enzyme. This precursor can also be processed by mitochondria into a form with the sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility of mature enzyme. The isolation of this precursor as a stable and catalytically active entity indicates that the presequence peptide does not necessarily interfere with much of the folding and basic structural properties of the mature protein component.
 ...
PMID:Isolation and properties of a liver mitochondrial precursor protein to aspartate aminotransferase expressed in Escherichia coli. 264 43

Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6-phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite.
 ...
PMID:Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. 290 Nov 47

Extracts of the leaf tissue of Panicum maximum Jacq. var. trichoglume Eyles (a phosphoenolpyruvate carboxykinase type of C4 plant) were examined and at least two isoforms of aspartate aminotransferase (EC 2.6.1.1), with different electrophoretic mobilities, were detected. The predominant isoform was purified to homogeneity from mesophyll cells. The purification procedure included fractionation with ammonium sulfate followed by chromatography on diethylaminoethyl-cellulose, Sephacryl S-300, and hydroxyapatite. The purified enzyme had specific activities of 182 and 165 mumol/min/mg protein, measured in terms of the synthesis of oxaloacetate and aspartate, respectively, at pH 8.0. The enzyme, with an apparent molecular size of 100 kDa, appears to be a dimer of a single polypeptide with a molecular size of 42 kDa. Mono specific polyclonal antibodies were raised against the 42-kDa polypeptide. Only a single stained band was detected in extracts of whole leaves by immunoblot analysis with this antibody after two-dimensional polyacrylamide electrophoresis. Furthermore, no difference in mobility was observed between the enzymes extracted from mesophyll and bundle sheath cells on native polyacrylamide gels. These findings are discussed in relation to the other isoform in the leaves of this species.
 ...
PMID:Aspartate aminotransferase from Panicum maximum Jacq. var. trichoglume Eyles, a C4 plant: purification, molecular properties, and preparation of antibody. 293 Jan 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>