Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the ubiquitous presence of p-xylene in air and the existing uncertainty regarding its hepatotoxic potential, we examined the effect of acute and short-term exposure to inhaled p-xylene on the liver. Male F-344 rats were exposed to 0 or to 1600 ppm p-xylene, 6 h/d, for 1 or 3 d. Exposure to inhaled p-xylene caused no histopathological evidence of hepatic damage and had little or no effect on the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, ornithine carbamyl transferase, alkaline phosphatase, and total bilirubin. Exposure to p-xylene for 1 or 3 d resulted in an increase in relative liver weight on d 1 post-exposure. The concentration of hepatic cytochrome P-450 was increased by both p-xylene exposure regimens on d 1 postexposure and had returned to control levels by d 3 following the single p-xylene exposure and by d 2 following the 3-d exposure. These observations provide consistent evidence that acute and short-term exposure to 1600 ppm p-xylene by inhalation did not produce overt hepatotoxicity but resulted in a significant increase in the concentration of hepatic cytochrome P-450, the principal enzyme system involved in the metabolic biotransformation of xenobiotics.
...
PMID:Assessment of the hepatotoxicity of acute and short-term exposure to inhaled p-xylene in F-344 rats. 200 13

Diets containing 0.8, 2.53 and 8.0% field variety morning glory seed were fed to male and female rats (20 per group) in a 90-day subchronic feeding study. Gross clinical observations, body weight, and feed and water intake were recorded weekly. At 90 days, all surviving rats were autopsied, organs were weighed, and blood chemistry analyses, haematology, and bone-marrow evaluation for evidence of clastogenic effects were performed. Tissues from control (0% seed) and high-dose (8.0% seed) rats were examined histologically. Effects of morning glory seed were noted mainly in the high-dose group of both sexes. These included increases in mortality, feed consumption (on a body-weight basis), water consumption, serum alkaline phosphatase and potassium, white blood cell count, and brain and liver weights (as a percentage of body weight); body-weight gain and serum glucose were decreased. Significant changes seen in high-dose females alone were: increased haemoglobin, serum constituents (urea nitrogen, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, and ornithine carbamyl transferase), and organ weights (heart, kidney, spleen and pancreas as a percentage of body weight), and decreases in serum albumin, total protein, albumin:globulin ratio, and calcium. Significant changes occurring in high-dose males alone were: increased testicular weight (as a percentage of body weight), increased serum phosphorus, and decreased serum cholesterol. Liver degeneration in the high-dose females was greater than that in the controls. Mortality at 8.0% seed in the diet was 40% in males and 10% in females. At 0.8% seed, the only parameter that differed significantly from that of the controls was a final body-weight reduction in females without a corresponding reduction in feed consumption.
...
PMID:Toxicological evaluation of morning glory seed: subchronic 90-day feeding study. 224 29

Elevated levels of serum enzymes are frequently associated not only with alcohol-related organ damage but also with excessive alcohol consumption and alcoholism without significant tissue injury. However, both in the early detection of alcoholism as well as also in the diagnosis of alcohol-related diseases the sensitivities and specificities of these enzyme markers vary considerably. They may be influenced by nonalcohol-related diseases, enzyme-inducing drugs, nutritional factors, metabolic disorders, age, smoking, etc. Consequently, we have neither a single laboratory test--enzyme marker--nor a test combination that is reliable enough for the exact diagnosis between alcohol- and nonalcohol-related organ damage. In most cases it is possible to determine the tissue from which the elevated enzyme is derived, but only occasionally enzyme changes reflect the quantity of the tissue injury. Gamma-glutamyltransferase (GGT) is the most widely used laboratory marker of alcoholism and heavy drinking, detecting 34-85% of problem drinkers and alcoholics. However, the unspecificity of increased serum GGT limits its use for general screening purposes. Its value in the follow-up of various treatment programs, however, is well established. An elevated level of serum aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in an alcoholic or a heavy consumer indicates alcohol-induced organ damage. The use of test combinations significantly improves the information received with single serum enzyme determinations. An ASAT/ALAT ratio greater than 1.5 can be considered as highly suggestive for the alcoholic etiology of the liver injury. Still better discrimination between alcoholic and nonalcoholic origin of the liver disease may be achieved by the determination of the ratio of GGT to alkaline phosphatase. If this ratio exceeds 1.4 the specificity of the finding in favor for alcoholic liver injury is 78%. The determination of the mitochondrial isoenzyme of ASAT also improves the diagnostic value of ASAT determination. The ratio of mitochondrial isoenzyme to total over 4 is highly suggestive for alcohol-related liver injury. In general, however, the determination of serum activities of other enzymes such as ornithine carbamyl transferase, lactate dehydrogenase, isocitrate dehydrogenase, sorbitol dehydrogenase, alcohol dehydrogenase, guanase, aldolase, alkaline phosphatase or glutathione S-transferase do not significantly improve the diagnostic information obtained with more conventional laboratory markers of liver injury.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Use of enzymes for the diagnosis of alcohol-related organ damage. 243 6

Serological tests may be of value in differentiating acute and chronic bile duct obstruction because the rate of alteration of hepatic cellular integrity and function will affect the rate of cellular product release. In a canine model the common bile duct was obstructed either suddenly (N = 7) or gradually (N = 5). A control group (N = 5) had the common bile duct dissected free from the surrounding tissues. Blood was taken before and 1, 2, 4, 7, 11, 14, 17, 21, and 28 days after initiating obstruction. Serum alkaline phosphatase, bilirubin, aspartate aminotransferase, alanine aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase levels were significantly greater with sudden compared to gradual occlusion, and the values were larger than those in the control. The range of values of alkaline phosphatase, bilirubin, and aspartate aminotransferase did not overlap in the acute and chronic groups at specific times. Serum albumin and total protein were normal in all groups. The magnitude of alkaline phosphatase, aspartate aminotransferase, and bilirubin elevation may help in the differentiation of acute and chronic biliary obstruction.
...
PMID:Diagnostic value of liver function tests in bile duct obstruction. 256 54

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
...
PMID:Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. 262 Jul 97

The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.
...
PMID:Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents. 286 77

X-ray crystallographic data have implicated Arg-292 as the residue responsible for the preferred side-chain substrate specificity of aspartate aminotransferase. It forms a salt bridge with the beta or gamma carboxylate group of the substrate [Kirsch, J. F., Eichele, G., Ford, G. C., Vincent, M. G., Jansonius, J. N., Gehring, H., & Christen, P. (1984) J. Mol. Biol. 174, 497-525]. In order to test this proposal and, in addition, to attempt to reverse the substrate charge specificity of this enzyme, Arg-292 has been converted to Asp-292 by site-directed mutagenesis. The activity (kcat/KM) of the mutant enzyme, R292D, toward the natural anionic substrates L-aspartate, L-glutamate, and alpha-ketoglutarate is depressed by over 5 orders of magnitude, whereas the activity toward the keto acid pyruvate and a number of aromatic and other neutral amino acids is reduced by only 2-9 fold. These results confirm the proposal that Arg-292 is critical for the rapid turnover of substrates bearing anionic side chains and show further that, apart from the desired alteration, no major perturbations of the remainder of the molecule have been made. The activity of R292D toward the cationic amino acids L-arginine, L-lysine, and L-ornithine is increased by 9-16-fold over that of wild type and the ratio (kcat/KM)cationic/(kcat/KM)anionic is in the range 2-40-fold for R292D, whereas this ratio has a range of [(0.3-6) x 10(-6)]-fold for wild type. Thus, the mutation has produced an inversion of the substrate charge specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Role of arginine-292 in the substrate specificity of aspartate aminotransferase as examined by site-directed mutagenesis. 316

Male F344 rats were exposed by gavage to samples of complex mixtures and evaluated 24 hr later. Seven of the 10 samples caused death at doses ranging from 1 to 5 ml/kg body wt. Eight of the 10 samples were hepatotoxic based on histopathologic evaluation; 6 were centrilobular and 2 were periportal hepatotoxicants. The waste samples exerted toxicity through different mechanisms, as indicated by differences in the severity and lobular location of the tissue damage. Nine of the 10 samples caused an increase in the ratio of liver weight to body weight (relative liver weight). With histopathological evaluation as the criterion, relative liver weight was the single best indicator of hepatotoxicity. Exposure to several of the waste samples increased serum total bilirubin and serum enzyme activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, and ornithine carbamyl transferase. As a battery, but not individually, the serum indicators separated the 8 hepatotoxic samples from the 2 nonhepatotoxic samples. In general, the hepatotoxicity of the waste samples did not appear to be readily predicted from (partial) chemical characterization data. An approach that includes both chemical characterization and biological testing should provide valuable information regarding the hazardous nature of complex wastes.
...
PMID:Lethality and hepatotoxicity of complex waste mixtures. 337 Dec 93

L-Hydrazinosuccinate has been shown to induce a marked inhibition of liver aspartate aminotransferase isoenzymes in mice. The effects of the drug on the amino acid content of liver were studied. Intraperitoneal administration of L-hydrazinosuccinate enormously increased the citrulline content of liver and plasma in 6 hr and, less markedly, increased the glutamate and ammonia content of liver with a simultaneous decrease in the aspartate content. Drug administration also induced a marked increase in the liver mitochondrial activity of citrulline formation from ornithine, ammonia and carbon dioxide, with a similar increase in N-acetylglutamate content; a prominent increase in liver tryptophan dioxygenase activity; and an elevated level of plasma corticosterone. The increase of citrulline was interpreted to be produced by decreased conversion of citrulline to argininosuccinate due to a lack of aspartate because of inhibition of aspartate aminotransferase by the drug and increased formation of citrulline due to increases of glutamate and ammonia, which further induced the increase of N-acetylglutamate, because of inhibition of aminotransferase as well as stimulation of amino acid degradation by glucocorticoids.
...
PMID:Citrulline accumulation in mice induced by administration of L-hydrazinosuccinate. 342 94

We evaluated the concept that the vascular entrance of both bacterial and nonbacterial particulate material could lead to hepatic parenchymal cell injury, either due to postphagocytic Kupffer cell activity or the margination of activated leukocytes in the liver. Injection of denatured, collagen-coated particles as well as heat-killed bacteria were used as particulate challenges. Hepatic parenchymal cell injury in vivo during postoperative sepsis was evaluated by plasma aspartate aminotransferase (AST) and ornithine carbamyl transferase (OCT) enzyme levels over 3-72 h. AST and OCT levels elevated following either laparotomy plus cecal ligation (mild sepsis) or laparotomy plus cecal ligation with puncture (severe sepsis), with the peak level at 24 h. In addition, the direct intravenous injection of either nonbacterial foreign particles or heat-killed Pseudomonas aeruginosa into normal rats also produced a dose-dependent elevation of AST and OCT. The plasma level of either AST or OCT actually increased 350-400% after injection of the non-bacterial particles. A similar dose related elevation in enzymes followed the intravenous injection of heat-killed Pseudomonas. To differentiate the potential contribution of activated hepatic Kupffer cells versus activated marginated neutrophils to the in vivo hepatic injury, we determined the release of the hepatic specific enzyme OCT by cultured hepatic parenchymal cells when they were exposed to isolated Kupffer cells or isolated PMNs that were activated by exposure to dead bacteria. Bacteria alone when added to cultured hepatocytes did not induce significant OCT release. In contrast, activated PMNs but not Kupffer cells induced a significant (p less than 0.05) release of OCT from parenchymal cells into the culture media. Thus, in vivo transient hepatic parenchymal cell injury with post-operative sepsis may be mediated by the margination of activated PMNs in the liver.
...
PMID:Hepatocyte injury during post-operative sepsis: activated neutrophils as potential mediators. 342 80


<< Previous 1 2 3 4 5 6 Next >>

---