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)

Chloroform (CHCl3) is widely used in the manufacture of drugs, cosmetics, plastics and cleaning agents. It is also found in chlorinated drinking water. This study was designed to investigate the toxic effect of CHCl3 on isolated male rat hepatocytes using several toxicity parameters. The hepatocytes were isolated by a collagenase perfusion technique and the cell viability was determined by Trypan blue exclusion. The leakage of cytosolic enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) after treatment with CHCl3 was measured. Reduced glutathione content (GSH) and its related enzymes, glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px), were also evaluated to study the effect of CHCl3 on hepatocytes. Exposure to 100 and 1000 ppm CHCl3 results in a significant decrease in cell after 30 min incubation. However, the effect of 1 and 10 ppm concentrations was observed at 60 min incubation. AST leakage was significantly increased in all treatment groups, while ALT was significantly increased at 100 and 1000 ppm CHCl3 after 60 and 30 min, respectively. As early as 15 min, GSH was decreased significantly at 1000 ppm, but at 100 and 10 ppm CHCl3 the decrease in GSH began after 30 and 120 min, respectively. GSH-Px activity did not changed. However, the activity of GSH-Rx was significantly decreased at 1000 ppm CHCl3 and at the same time GSH content was decreased. The data indicate that the toxic effect of CHCl3 was dose- and time-dependent. The degree of GSH depletion correlated with increased cytotoxicity and decreased GSH-Rx activity due to CHCl3.
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PMID:The mechanism of chloroform toxicity in isolated rat hepatocytes. 835 69

If the pyridoxal-phosphate-binding lysine residue 258 of aspartate aminotransferase is exchanged for a histidine residue, the enzyme retains partial catalytic competence [Ziak, M., Jaussi, R., Gehring, H. and Christen, P. (1990) Eur. J. Biochem. 187, 329-333]. The three-dimensional structures of the mutant enzymes of both chicken mitochondria and Escherichia coli were determined at high resolution. The folding patterns of the polypeptide chains proved to be identical to those of the wild-type enzymes, small conformational differences being restricted to parts of the active site. If aspartate or glutamate was added to the pyridoxal form of the mutant enzyme [lambda max 392 nm and 330 nm (weak); negative CD at 420 nm, positive CD at 370 nm and 330 nm], the external aldimine (lambda max = 430 nm; negative CD at 360 nm and 430 nm) transiently accumulated. Upon addition of 2-oxoglutarate to the pyridoxamine form (lambda max 330 nm, positive CD), a putative ketamine intermediate could be detected; however, with oxalacetate, an equilibrium between external aldimine and the pyridoxal form, which was strongly in favour of the former, was established within seconds. The transamination cycle with glutamate and oxalacetate proceeds only three orders of magnitude more slowly than the overall reaction of the wild-type enzyme. The specific activity of the mutant enzyme is 0.1 U/mg at 25 degrees C and constant from pH 6.0 to 8.5. Reconstitution of the mutant apoenzyme with [4'-3H]pyridoxamine 5'-phosphate resulted in rapid release of 3H with a first-order rate constant kappa' = 5 x 10(-4) s-1 similar to that of the wild-type enzyme. Apparently, in aspartate aminotransferase, histidine can to some extent substitute for the active-site lysine residue. The imidazole ring of H258, however, seems too distant from C alpha and C4' to act efficiently as proton donor/acceptor in the aldimine-ketamine tautomerization, suggesting that the prototropic shift might be mediated by an intervening water molecule. Transmination of the internal to the external aldimine apparently can be replaced by de novo formation of the latter, and by its hydrolysis in the reverse direction.
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PMID:Mutant aspartate aminotransferase (K258H) without pyridoxal-5'-phosphate-binding lysine residue. Structural and catalytic properties. 843 9

An investigation on the relative presence of some protein metabolic enzymes, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), NAD+ and NADP+ dependent glutamate dehydrogenase (GLDH) and arginase in cyst wall (CW), cyst fluid (CF) and zoite (ZT) fractions of the sarcocysts of Sarcocystis fusiformis in the oesophageal muscles of Indian water buffalo was carried out. Both the transaminases were present in all the fractions of the cyst, although in variable amounts. There was a higher level of AST activity than of ALT activity. AST activity was the highest in ZT, whereas ALT activity was at a maximum in the CF fraction. The levels of activity of NAD+ and NADP+ dependent GLDH and arginase remained beyond detectable limits. The study revealed that the intermediates of carbohydrate metabolism are linked to protein metabolism by transaminases. The possibility of concomitant removal of ammonia and its subsequent incorporation into the urea cycle is ruled out in this parasitic protozoan.
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PMID:Sarcocystis fusiformis: some protein metabolic enzymes in various fractions of sarcocysts of buffalo (Bubalus bubalis). 844 61

RNA, DNA, total protein, transketolase (TK), alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), methionyl-tRNA (met-tRNA)- and cysteinyl-tRNA (cys-tRNA)-synthetases in the thymus and spleen of 46 intact rats exposed to hypokinesia and vitamin B1 deficiency were measured. It was found that 15-day hypokinesia induced a significant decrease of the thymus and spleen weight and an increase of AlAT in the thymus. Vitamin B1 deficiency (hydroxy thiamine in drinking water at a dose of 2 mg/kg body weight for 15 days) led to a substantial decrease of TK in blood, AlAT and AsAT in the spleen; it diminished AsAT and increased AlAT in the thymus. Combined exposure to hypokinesia and vitamin B1 deficiency caused a more marked decrease of the weight of lymph organs, a significant loss of body weight, an increase of DNA in the thymus and spleen, and an increase of TK, met-tRNA-synthetase and AlAT in the thymus. These results suggest that vitamin B1 deficiency aggravates disorders in protein and nucleic acid metabolism in the lymph organs of hypokinetic animals.
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PMID:[Several indicators of protein and nucleic acid metabolism in lymphoid organs of rats exposed to hypokinesia and vitamin B1 deficiency]. 857 40

The study was performed on 4 groups of male Wistar rats, receiving p.o. through 3 months every day: 1). Sodium nitrite in dose 30 mg/kg b.w. x day (0.2 LD50); 2). Cupric chloride in dose 4.67 mg/kg b.w. x day (0.03 LD50); 3 ). Cupric chloride and sodium nitrite in amounts as above, and 4). Control group--received dest. water. The activity of alanine aminotransferase (AlAT), aspartate aminotransferase (AspAT), gamma-glutamyltransferase (GGTP-ase) and creatinine and urea level in blood plasma were determined 24 hours after the last application of compounds. There was showed, that every day rats' intoxication with sodium nitrate during 90 days caused the significant increase of gamma-glutamyltransferase activity and decrease of urea level in the blood plasma. Subchronic exposure to copper and copper with sodium nitrate causes no effect on biochemical parameters were studied.
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PMID:[Evaluation of the combined effect of cupric chloride and sodium nitrite on selected biochemical parameters in rat plasma (subchronic exposure)]. 861 20

1. Broiler breeder females were fed ad libitum, or according to a commercial food restriction programme or to gain 0.85, 0.70, 0.55, 0.40 or 0.25 of the body weight of ad libitum-fed birds. Several indices of the welfare of the birds were assessed at 3-weekly intervals to 18 weeks of age and related to body weight by regression analysis. Results for 6, 12 and 18 weeks of age are presented in detail. 2. Water intake was consistently higher in the 0.25, 0.40 and commercial restriction treatments. 3. There was a negative curvilinear relationship at each age group between body weight and the heterophil-lymphocyte ratio and plasma corticosterone concentration. 4. There was a positive relationship between the plasma concentration of creatine kinase and body weight at 12 and 18 weeks of age. The relationships between body weight and the plasma activity of alkaline phosphatase and aspartate transaminase changed with the age and there were no differences between treatments for lactate dehydrogenase. 5. The time spent resting increased with body weight at each age. The relationship between time spent preening and body weight changed with age whereas that for oral activities was similar among restricted birds at 6, and among all treatments at 12 weeks of age. At 18 weeks there was an increase in oral activities with decreasing body weight. 6. Fearfulness was positively related to body weight. The response of the comb to phytohaemagglutinin injection was similar in all treatments and the antibody titre to injections of sheep red blood cells was curvilinear. 7. A principal components analysis of all measured traits at 6, 12 and 18 weeks of age was conducted. Most of the variables were redundant but at least one from each of the different classes of welfare indices was retained at 6 and 12 weeks of age. 8. It was concluded that a body weight during rearing in the range of 0.5 to 0.85 of ad libitum might provide for optimum welfare of broiler breeder females.
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PMID:Relationships between the degree of food restriction and welfare indices in broiler breeder females. 877 36

An 11-month-old female Vietnamese pot-bellied pig was examined for severe dehydration and neurologic signs including disorientation, ataxia, blindness, and involuntary twitching of the muscles of the neck and head. Biochemical analyses of serum revealed hypernatremia, hyperchloremia, hyperkalemia, azotemia, hyperphosphatemia, hyperalbuminemia, and high activities of aspartate transaminase and creatine kinase. A diagnosis of salt toxicosis/water deprivation was made. Medical management consisted of intravenous administration of a high-sodium crystalloid solution, anti-inflammatory drugs, and other supportive care. Sodium concentration of fluids administered intravenously was adjusted to be slightly less than the pig's serum sodium concentration so that the serum sodium concentration was reduced gradually over 48 hours. Resolution of clinical signs was rapid and the pig was discharged after 8 days of hospitalization. Fourteen days after the initial examination, the pig appeared healthy except for visual deficits. Historically, prognosis with conventional treatment of salt toxicosis/water deprivation is poor; however, this alternative approach to treating this condition appears promising.
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PMID:High-sodium crystalloid solution for treatment of hypernatremia in a Vietnamese pot-bellied pig. 883 48

Mitochondrial aspartate aminotransferase is a homodimeric protein with 2 x 402 amino acid residues. The enzyme in solution undergoes ligand-induced and syncatalytic conformational changes which appear to correspond to shifts in the equilibrium between the crystallographically defined open and closed conformation. In the closed conformation, the small domain of each subunit has rotated as a rigid body by 13 degrees and 14 degrees towards the large coenzyme-binding domain and has closed the active-site pocket. Molecular dynamics simulations at 300 K of 120-ps duration were started from the crystal structures of the unliganded pyridoxal form (open form) of the dimeric enzyme and the 2-methylaspartate-liganded closed form in which the 2-methyl group had been removed. Both structures contained the crystal water molecules and were placed in a 5-A shell of water. The rms fluctuations of the individual C alpha atoms during the simulations agreed well with the corresponding B factors of the crystal structures. Superposition of the initial structures and the average structures of the last 20 ps showed in both simulations extensive C alpha deviations in the case of the whole subunit but much smaller changes in the individual large and small domains, indicating a movement of the two domains relative to each other. In the simulation of the open form, superposition of the large domains made evident a displacement of the small domain towards its position in the closed crystal structure, which can be described by a rotation of the small domain by about 13 degrees around the twofold symmetry (z) axis. A significantly less extensive rearrangement of parts of the small domain, i.e. a rotation of about 5 degrees around the z axis, was observed in the simulation of the substrate-liganded enzyme (closed form) which, in contrast to the open form, showed only small conformational changes around the active site. In both simulations an additional rotation of the small domain by 9 degrees around the x axis occurred. The actual domain movement is estimated to occur in a time range at least two orders of magnitude larger than the simulation time of 120 ps. Apparently, the surface tension of the unrestrained nonspherical shell of water accelerates the simulated conformational change which, however, quite closely imitates the geometric features of the extensive movement of the small domains (each approximately 130 residues).
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PMID:Molecular-dynamics simulation of domain movements in aspartate aminotransferase. 885 80

Thirty-four horses competing in the Endurance Test of a 3-day-event were divided into 3 groups: horses in Group 1 (n = 15) competing in a 3.5 min steeplechase phase; horses in Group 2 (n = 13) in a 3 min steeplechase phase (Phase B) and horses in Group 3 (n = 6) in a 2.5 min steeplechase phase. The shortening of Phase B was associated with a lengthening of Phase C so that the total distance of the event for all horses was 14,940 m. Bodyweight (BW) was measured and total body water (TBW) and water loss estimated. Blood samples were collected from the horses prior to the Endurance Test, at the end of Phase B, the 4 km marker on Phase C (C4K), the end of Phase C, and 20 min after the completion of Phase D for measurement of packed cell volume (PCV), total plasma protein [TPP], lactate, ionised calcium, pH, sodium, potassium, chloride, total calcium and glucose concentrations, and aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities. Mean +/- s.d. ambient environmental temperature during the Endurance Test was 25.3 +/- 1 degrees C (range 20.3 degrees C-29.7 degrees C). Mean relative humidity was 43.8 +/- 2.4% (range 39%-48.6%) and the average 'comfort index' (CI) was 121. There were no significant differences between the groups competing in the Endurance Test, despite the shorter Phase B. However, there were significant decreases in BW, TBW, net exchangeable cations, chloride, ionised calcium, and pH. The sodium and total calcium concentrations remained at near pre-event values. The PCV, TPP, lactate, potassium, glucose, aspartate aminotransferase, and lactate dehydrogenase activity increased during the Endurance Test, when compared to pre-event values. Horses competing in this competition experienced significant fluid and electrolyte losses, reduced glomerular filtration, increased glycogenolysis and had significant leakage of enzymes from working muscles during competition. These changes could not be reduced by shortening Phase B and lengthening Phase C.
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PMID:Effects of shortening the steeplechase phase (phase B) of a 3-day-event. 893 87

The effects of insulin and the insulin mimetic agent "vanadate" were studied on the activities of alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and arginase in the cytosolic and the mitochondrial fractions of the kidney in control and alloxan induced diabetic rats. An enhancement in the activities of these enzymes were noted in both the fractions of diabetic kidney. Vanadate treatment (0.6 mg/ml in drinking water) of alloxan induced diabetic rats restored the activities of these enzymes almost completely in the cytosolic and partially in the mitochondrial fractions. Vanadate treatment also normalized hyperglycaemia without altering the depressed levels of insulin secretion in diabetic rats. The effect of insulin treatment was found to be the same as that of vanadate in diabetic rats.
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PMID:Effects of vanadate and insulin on the activities of selected enzymes of amino acid metabolism in alloxan diabetic rat kidney. 895 44


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