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)

A 2 x 2 x 2 factorial arrangement of treatments consisting of dietary aflatoxin (3.5 micrograms/g), ochratoxin A (2.0 micrograms/g), and hydrated sodium calcium aluminosilicate (HSCAS, .5%) was used to evaluate the individual and combined effects of these treatments. There were six replicate pens of 10 broilers per pen for each of the eight treatments. The broilers were maintained on these treatments from 1 day to 3 wk of age with feed and water available for ad libitum intake. Aflatoxin and ochratoxin A each significantly decreased body weight, serum protein, albumin, and cholesterol and increased the relative weight of the liver, kidney, and proventriculus. Aflatoxin increased the relative weight of the heart and decreased serum aspartate aminotransferase activity and ochratoxin A increased serum uric acid. The toxicity resulting from the combination of aflatoxin and ochratoxin A was more severe than when either of these mycotoxins were present alone. Addition of HSCAS alone did not alter any of the parameters evaluated. The HSCAS reduced the toxicity of aflatoxin, but had little effect on either the toxicity of ochratoxin A alone or the toxicity resulting from the combination of aflatoxin and ochratoxin A.
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PMID:Efficacy of hydrated sodium calcium aluminosilicate to reduce the individual and combined toxicity of aflatoxin and ochratoxin A. 131 50

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.
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PMID:Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. 133 43

This retrospective analysis tests the hypothesis that topical cardiac hypothermia is an unnecessary adjunct to intraoperative myocardial protection and an avoidable cause of pulmonary morbidity in patients with coronary disease receiving blood cardioplegia. The hospital records of 150 nonrandomized consecutive patients undergoing elective and emergency isolated coronary revascularization were reviewed. All patients received multidose cold blood cardioplegia followed by warm blood cardioplegic reperfusion distributed through grafts. Fifty patients received iced slush, 50 received topical 4 degrees C saline, and no topical cooling was used in 50 others. Patients groups were comparable in number of grafts (3.7 versus 3.5 versus 3.5) and crossclamp time (61 versus 62 versus 61 minutes). More emergency operations were performed in the patients receiving no topical hypothermia (12/50 versus 8/50 versus 7/50). Postoperative x-ray films were reviewed by a radiologist who did not know of patient grouping. Postoperative results were comparable in hemodynamics, inotropic requirements (10/50 ice versus 8/50 saline versus 5/50 no cooling), myocardial infarction (1/50 versus 2/50 versus 2/50), and enzymes (aspartate aminotransferase myocardial band creatine kinase). No patient died. Ice topical hypothermia (versus no topical cooling) was associated with more left pleural effusions (25/50 versus 9/50; p less than 0.05), atelectasis (33/50 versus 18/50; p less than 0.05), elevated left hemidiaphragms (13/50 versus 0/50; p less than 0.05), and longer postoperative hospitalization (11.2 versus 8.5 days; p less than 0.05). Topical 4 degrees C saline reduced diaphragmatic elevation and pleural effusion (versus topical ice) but was associated with more atelectasis (34/50 versus 18/50; p less than 0.05) than no topical cooling. These data suggest that routine topical hypothermia is an unnecessary adjunct to blood cardioplegic protection in patients with coronary disease, since supplemental topical cooling does not improve postoperative hemodynamics or reduce inotropic requirements, enzyme release, or prevalence of postoperative myocardial infarction, and it increases pulmonary morbidity, which can be reduced by its avoidance.
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PMID:Topical cardiac hypothermia in patients with coronary disease. An unnecessary adjunct to cardioplegic protection and cause of pulmonary morbidity. 151 52

Groups of 20 rats and 20 mice of each sex were administered monochloroacetic acid (MCAA) once daily, 5 days per week, in water by gavage for up to 13 weeks. Doses used were 0, 30, 60, 90, 120, or 150 mg/kg for rats and 0, 25, 50, 100, 150, or 200 mg/kg for mice. Compound-related deaths occurred at the four highest dose levels in rats and at the highest dose level in mice. Mean body weights of treated groups of rats and mice surviving until the end of the study were similar to those of the controls. A dose-related increase in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, as well as a dose-related increase in the relative liver and kidney weights was observed in rats but not in mice. A dose-related increase in the incidence and severity of cardiomyopathy occurred in rats. This lesion may be related to the inhibition of heart mitochondrial aconitase activity. No compound-related lesions were observed in mice. The results of this study indicate that F344 rats are more sensitive than B6C3F1 mice; sexes within the species were equally sensitive. The no-observable-effect level was estimated as 30 mg MCAA/kg body weight for rats and 100 mg MCAA/kg body weight for mice.
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PMID:Toxicity of monochloroacetic acid administered by gavage to F344 rats and B6C3F1 mice for up to 13 weeks. 153 74

Observation of the 93-kDa cytosolic aspartate aminotransferase by 500-MHz 1H NMR spectroscopy in H2O has revealed a series of resonances in the 10-18 ppm range arising from exchangeable protons. One of these (peak A) has been assigned to the proton bound to the ring nitrogen of the coenzyme pyridoxal 5'-phosphate. A second (peak B) is assigned to H143 which participates in a chain of hydrogen bonds that includes also the coenzyme-bound proton. There is a mutual nuclear Overhauser effect between these two resonances. Peaks A and B respond to changes in pH and to interaction of the enzyme with coenzyme derivatives and inhibitors. Peak A moves from 15.4 to 17.4 ppm as the pH is lowered, while peak B moves in the opposite direction from 14.7 to 13.7 ppm, both with an apparent pKa of 6.15. This pKa is associated with deprotonation of the imine nitrogen at the Schiff base linkage of the coenzyme with K258 of the enzyme. In spectra of enzyme containing pyridoxamine 5'-phosphate, peak A is observed at 16.5 ppm and peak B is at 13.9 ppm over a broad pH range. Peaks A and B are found at 17.8 and 14.0 ppm, respectively, for the enzyme complex with glutarate. When alpha-methylaspartate is added to the enzyme several new resonances appear in the spectrum, which are attributed to formation of the external aldimine. The position of peak A in spectra of various forms of the enzyme is interpreted to reflect the electronic distribution in the coenzyme ring. Several other peaks in this region of the spectrum also are sensitive to changes in pH or the addition of inhibitors. Some possible assignments of these resonances are discussed.
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PMID:NMR observation of exchangeable protons of pyridoxal phosphate and histidine residues in cytosolic aspartate aminotransferase. 165 26

The aspartate aminotransferase mutant Y70F exhibits kcat = 8% and kcat/KM = 2% of the wild type values for the transamination of aspartate and alpha-ketoglutarate. The affinity of the enzyme for the noncovalently bound inhibitor maleate is reduced 17-fold by the mutation, while only a 2.5-fold reduction is observed for alpha-methylaspartate, which forms a stable, covalent external aldimine. The high population of the quinonoid intermediate formed in the reaction of the wild type with beta-hydroxyaspartate is more than 75% diminished by the mutation. The values of the Y70F C alpha-H kinetic isotope effects for the aspartate reaction are larger than those of wild type (DV = 2.4 vs 1.52; D(V/K) = 2.5 vs 1.7). Conversely, the Y70F value of D(V/K) for the glutamate reaction is decreased compared to wild type (1.75 vs 2.5). These results, combined with previous studies of Lys258 mutants, eliminate Tyr70 as an essential component of the catalytic apparatus, with the caveat that the functionally of the deleted hydroxyl group is possibly replaced by a water molecule.
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PMID:Tyrosine 70 fine-tunes the catalytic efficiency of aspartate aminotransferase. 167 69

Dose- and time-related effects of Cd (II) (0.5 or 1.0 mg/kg, Cd as CdCl2.H2O, subcutaneously, daily for 48 h, 1, 3, or 6 wk) were investigated in rats. A dose-related increase in the activity of plasma alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) was evident only at 6 wk, whereas an early rise in ALP and LDH was seen at 3 wk in 1.0 mg Cd group only. The hepatic and renal metallothionein (MT) induction displayed a dose- as well as time-related increase with Cd accumulation. A significant increase in hepatic Zn and renal Cu, no change in hepatic Cu, and a slight increase in renal Zn was observed. Urinary ALP and leucine aminopeptidase (LAP) showed an initial increase at 48 h, thereafter returned to near normal. A second phase of enzymuria (ALP, LAP, GOT, GPT, gamma-glutamyl transpeptidase), proteinuria, and aminoaciduria occurred at 6 wk in a dose-related manner. The urinary excretion of specific renal enzymes appeared closely related to the MT induction and organ Cd levels.
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PMID:Biochemical response to cadmium. Dose-time effect. 171 72

Aspartate aminotransferase (mitochondrial isoenzyme from chicken) has been found to racemize very slowly dicarboxylic amino acid substrates in the presence of their cognate oxo acids [Kochhar, S. & Christen, P. (1988) Eur. J. Biochem. 175, 433-438]. Tyrosine, phenylalanine and alanine are racemized at the same rate although they undergo the transamination reaction 3-5 orders of magnitude more slowly than the dicarboxylic substrates. Similarly, the truncated enzyme aspartate aminotransferase-(27/32-410) catalyzes the racemization at the same rate as the native enzyme, while its rate of transamination is decreased to 3% of that of the native enzyme. Apparently, the rate-limiting step in racemization is not immediately linked to the transamination cycle. Decreasing the water concentration in the reaction medium by adding methanol at 0 degrees C drastically reduces the rate of racemization without affecting the rate of transamination. On the basis of these and additional kinetic data and the model of the three-dimensional structure of the active site, we conclude that a water molecule is responsible for the protonation of C alpha of the coenzyme-substrate intermediate from the wrong side. The diffusion of the water molecule into the interior of the enzyme appears to be the rate-limiting step in aspartate-aminotransferase-catalyzed racemization.
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PMID:Mechanism of racemization of amino acids by aspartate aminotransferase. 173 41

The photocoagulating properties of the water-jet-cooled Nd:YAG laser (1,064 nm) have been studied in a rat tumor model. A colon carcinoma CC531 was implanted in the liver; 20 days after inoculation, laser therapy was performed with 600 J, 850 J, 1,200 J, 1,700 J, or 2,400 J at a power setting of either 10 or 20 W. Liver damage was determined in tissue specimen on day 1 after treatment and by serum levels of alanine aminotransferase and aspartate aminotransferase on day 1 and 2. Tissue specimen of day 36 were used to evaluate tumor remission. Liver function was assessed by antipyrine clearance on day 2. Light microscopic examination on day 1 showed coagulative necrosis up to 10 mm in diameter at 1,700 J and 20 W. At 20 W, liver damage was 22% larger than at 10 W (P = 0.0001). A significant relationship was found between laser energy and liver damage with complete tumor destruction in all animals at 2,400 J. No deterioration in liver function was found. The results of this study show the ability of the water-jet-cooled Nd:YAG laser to produce tumor coagulation necrosis with minor liver damage.
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PMID:Water-jet-cooled Nd:YAG laser coagulation: selective destruction of rat liver metastases. 181 80

Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed feed, was added to the diets of growing wethers (mean body weight, 34.0 kg) and was evaluated for its ability to diminish the clinical signs of aflatoxicosis. The experimental design consisted of 4 treatment groups of 5 wethers each, consuming concentrations of 0 g of HSCAS and 0 g of aflatoxin (AF)/kg of feed (control; group 1); 20 g of HSCAS/kg (2.0%; group 2), 2.6 mg of AF/kg (group 3); or 20 g of HSCAS (2.0%) plus 2.6 mg of AF/kg (group 4). Wethers were maintained in indoor pens, with feed and water available ad libitum for 42 days. Lambs were observed twice daily and weighed weekly, and blood samples were obtained every 2 weeks for hematologic and serum biochemical analyses and for measurement of mitogen-induced lymphocyte-stimulation index. At the termination of the study, wethers were euthanatized and necropsied. Body weight gain was diminished significantly (P less than 0.05) by consumption of 2.6 mg of AF/kg of feed, whereas body weight of lambs consuming HSCAS plus AF did not differ from that of control wethers. The AF-alone treatment increased serum aspartate transaminase and gamma-glutamyltransferase activities, prothrombin time, and cholesterol, uric acid, and triglyceride values and decreased albumin, glucose, and urea nitrogen values, and urea-to-creatine ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diminution of aflatoxin toxicity to growing lambs by dietary supplementation with hydrated sodium calcium aluminosilicate. 185 May 85


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