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 five cysteines, at positions 82, 191, 192, 270, and 401, of Escherichia coli aspartate aminotransferase (AATase) were, individually and in some combinations, converted to alanine by site-directed mutagenesis (C82A, C191A, C192A, C270A, C401A). Cys-191, which is conserved in all AATase isozymes, was mutated to serine as well (C191S). A quintuple mutant, with all cysteines converted to alanines (Quint), was also constructed. The effects of these single and multiple mutations were examined by steady-state kinetics and urea denaturation. The thermal stabilities of Quint and of the wild-type enzyme (WT) were determined by differential scanning calorimetry. The mutants had kcat values up to 50% greater than that of WT and KMAsp and KM alpha-KG values up to 1.5- and 3.3-fold higher than that of WT. The mutants C82A and C191A exhibit nearly the same CM in urea denaturation experiments as WT, while the other single mutants and Quint are less stable, with CM differences of up to 0.7 M urea. Quint is also less thermostable than WT, with a delta TM of 3.3-4.4 degrees C. Thus the five cysteine replacements yield small, but significant, changes in catalytic and denaturation parameters, but none of the cysteines was found to be essential. The changes manifested in the mutation of the conserved Cys-191 to alanine are no greater than those observed with the four nonconserved cysteines. We consider the evolutionary implications of these findings.
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PMID:Contribution to catalysis and stability of the five cysteines in Escherichia coli aspartate aminotransferase. Preparation and properties of a cysteine-free enzyme. 173 83

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

In 1983 and 1984 blood was collected from 79 cottontail rabbits (Sylvilagus floridanus) confined to an outdoor enclosure in southern Illinois to establish reference values for hematology and serum chemistry. Packed cell volume, sodium, potassium, chloride, glucose, calcium, carbon dioxide, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, bilirubin, alkaline phosphatase, aspartate transaminase, alanine aminotransaminase, total protein, albumin/globulin ratio, and osmolality were measured. Sex and age (adult versus juvenile) of rabbit as well as season (June to September versus October to May) and method of capture (trap versus shot) variously affected most hematology and serum chemistry variables.
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PMID:Hematology and serum chemistry of cottontail rabbits of southern Illinois. 175 30

A number of toxic chemicals affect the biliary excretory function of liver. Organochlorines and halomethanes are known to enhance bile flow. Despite the demonstration that a diversity of agents modify biliary function, the mechanism by which these chemicals manifest this effect is not fully understood. This study was designed to assess the effect of colchicine (0.1, 1.0, or 2.5 mg/kg, i.p., in saline) administration on biliary excretory function 6 and 24 hr later. Additionally, the effect of colchicine (1 mg/kg, i.p. in saline) pretreatment in rats 2 hr prior to the administration of a single low dose of CCl4 (100 microL/kg, i.p., in corn oil) or corn oil alone (1 mL/kg, i.p.) on hepatic biliary excretory function was also assessed at 6 and 24 hr after the last treatment. The hepatotoxicity was evaluated by serum enzymes, alanine and aspartate aminotransferases, and histopathological alterations of the liver. Biliary excretion of intravenously administered phenolphthalein glucuronide (PG) was assessed in bile duct cannulated anesthetized rats. Only the highest dose of colchicine (2.5 mg/kg) resulted in detectable liver injury as revealed by elevations of serum transaminases. While the lowest dose of colchicine (0.1 mg/kg) did not influence bile secretion, the two higher doses caused a slight choleretic effect at 24 hr. The highest dose caused a transient inhibition of bile flow, but this effect was no longer evident at 6 hr. Biliary excretion of PG was inhibited significantly by colchicine within 6 hr after administration, an effect that was also persistent at 24 hr. Colchicine at a 1 mg/kg dose did not cause any adverse effect on hepatobiliary function. Therefore, for the interactive toxicity study with CCl4, 1 mg colchicine/kg was chosen as a moderate dose which did not cause any significant adverse effect on hepatobiliary function. Biliary excretion of PG was significantly lower in rats at 6 and 24 hr after the combination treatment with colchicine + CCl4 than in rats receiving either CCl4 or colchicine alone. In contrast, rats receiving CCl4 alone or colchicine + CCl4 showed a significant increase in cumulative bile flow at 6 hr, whereas, at 24 hr, the bile flow was increased significantly in rats receiving colchicine regardless of CCl4 treatment. The data suggest that colchicine pretreatment leads to significant inhibition of hepatobiliary excretion in CCl4 treated rats. Serum alanine transaminase and aspartate transaminase levels were elevated significantly after the colchicine + CCl4 combination, indicating hepatic injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of colchicine on hepatobiliary function in CCl4 treated rats. 176 17

The tryptophan-load test for vitamin B-6 nutritional status was administered to adult female Long-Evans rats fed graded levels of pyridoxine hydrochloride (PN.HCl) in two experiments, and its sensitivity to marginal vitamin B-6 intake was evaluated. In Experiment 1, rats were 4-h meal-fed an AIN-76A (20% casein) diet devoid of PN.HCl for 3 wk, then repleted (n = 12) for 6 wk with 4-h pair-fed meals of either 0.25, 0.5, 1.0 or 7.0 (control) mg PN.HCl/kg diet. In Experiment 2, rats (n = 16) were pair-fed for 10 wk either 0.0, 0.5, 1.0 or 7.0 (control) mg PN.HCl/kg diet, with 24-h access to food. Vitamin B-6 nutritional status was assessed at the end of each experiment. Except in rats fed 0 mg PN.HCl/kg diet, mean body weights were not significantly different among diet groups of either experiment. Plasma pyridoxal phosphate (PLP), pyridoxal and total vitamin B-6 concentrations, determined by HPLC, were very sensitive to gradations in dietary PN.HCl concentrations (P less than 0.05). Red blood cell endogenous and PLP-stimulated alanine and aspartate aminotransferase activity did not statistically differentiate all levels of dietary vitamin B-6, although the calculated activity coefficient for each enzyme (stimulated/endogenous activity) did. Urinary xanthurenic acid excretion following a tryptophan load [24.5 mumol (5 mg) L-tryptophan/100 g body weight, injected intraperitoneally] was significantly (P less than 0.05) elevated compared with controls only in the group fed 0 mg PN/HCl/kg diet. At the tryptophan dose used here, the tryptophan-load test was not useful in detecting marginal vitamin B-6 intake in rats.
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PMID:Insensitivity of the tryptophan-load test to marginal vitamin B-6 intake in rats. 176 28

We present the results of the treatment with ursodeoxycholic acid (UDCA, 7-9 mg/kg body weight daily) of 17 patients with primary biliary cirrhosis (8 in stages I-II; 9 in stages III-IV). At two months the mean values of alkaline phosphatase, gammaglutamiltranspeptidase, alanine and aspartate aminotransferase were reduced (p less than 0.001, p less than 0.001, p less than 0.01 and p less than 0.01 respectively). This improvement persisted without increase during the first year. At two months the total bilirubin value was reduced (p less than 0.01) associated with a reduction in the conjugated fraction (p less than 0.05). Cholesterol and gammaglobulin mean values also decreased at two months (p less than 0.05). We found no changes in IgM levels and antimitochondrial antibody titers. The improvement was similar in both groups (early I-II and advanced III-IV stages) and the treatment showed no undesirable effects either in early or advanced stages. Almost all the patients with pruritus (6 out of 7) improved with the treatment and the use of cholestyramine was reduced in all.
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PMID:[The treatment of primary biliary cirrhosis with ursodeoxycholic acid. The short- and median-term results and their relation to the study of the disease]. 176 69

The subcellular localization of NAD- and NADP-linked glutamate dehydrogenases (GDH-NAD and GDH-NADP), alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) in epimastigotes of Trypanosoma cruzi was studied by digitonin extraction from whole cells, subcellular fractionation by differential centrifugation and isopycnic ultracentrifugation. All enzymes presented both a cytosolic and a mitochondrial form; in addition, GDH-NADP seems to have a third, still undefined, localization. The results are compatible with the existence of two pathways for the production of L-alanine linked to the reoxidation of glycolytic NADH, one operative in the mitochondrion and the other in the cytosol, and perhaps responsible for the existence of the two alanine pools detected by 13C-nuclear magnetic resonance (B. Frydman et al., Eur. J. Biochem. 192 (1990) 363-368).
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PMID:Subcellular localization of glutamate dehydrogenases and alanine aminotransferase in epimastigotes of Trypanosoma cruzi. 177 28

To study the effects of ethanol on the hepatotoxicity of N-nitrosodimethylamine (NDMA), 5 mg NDMA/kg body weight was injected intraperitoneally 3 times a week for 6 weeks into rats pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrates. Another group of rats was pair-fed with the same diets but injected with saline instead of NDMA. Co-administration of ethanol and NDMA produced much higher elevations of serum alanine and aspartate aminotransferase and glutamic dehydrogenase activities than the administration of either agent alone. The combined treatment also slightly increased focal necrosis, whereas other liver lesions (steatosis and fibrosis) and the functional impairment of mitochondrial respiration were not affected significantly. Microsomal low Km NDMA demethylation, as well as NDMA denitrosation, were inhibited markedly by incubation with an antibody against P450IIE1, suggesting the involvement of this alcohol-inducible P450 in both NDMA bioactivation reactions. The addition of ethanol inhibited P450-dependent demethylation and denitrosation of NDMA in liver microsomes, whereas both activities were enhanced markedly by chronic ethanol administration. At ethanol concentrations similar to those prevailing in the blood of alcohol-fed animals at the time of NDMA administration, hepatic microsomal demethylation and denitrosation remained significantly higher in ethanol-fed rats given NDMA than in controls. Our results suggest that bioactivation plays a critical role in the hepatotoxicity of NDMA and its aggravation by chronic alcohol consumption.
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PMID:Effects of ethanol consumption on bioactivation and hepatotoxicity of N-nitrosodimethylamine in rats. 185 64

Kochia scoparia (L.) Schrad. is a prospective forage crop for arid areas, although its potential value is constrained by occasional toxicity that may involve alteration of metabolic hormones. The present research compared serum clinical profiles and metabolic hormone concentrations in steers and wethers fed kochia hay (85% OM, 13% CP, 45% ADF, and 6.3% total oxalate) to those of suitable controls that were pair-fed equal amounts of DM as alfalfa hay (91% OM, 13% CP and 42% ADF). Eight steers (240 +/- 2 kg BW) that were pair-fed kochia or alfalfa hay for 21 d had similar levels of serum insulin (INS) or somatotropin (GH), but kochia lowered prolactin (PRL) (6.0 vs 118 ng/ml; P = .14). Kochia hay did not elevate serum bilirubin at d 21 in these steers; however, lactic dehydrogenase and aspartate aminotransferase activities were elevated 1.3-fold (P less than .05). Ten fine-wool wethers (29 +/- kg BW) pair-fed kochia or alfalfa hay for 21 d had similar levels of PRL and INS at d 0, 5, 10, and 21; however, GH was lower in wethers fed kochia at d 5 (P less than .05) and somewhat lower at d 10 and 21. Kochia elevated serum unconjugated bilirubin 1.25-fold over pair-fed controls (P = .06) and increased (P less than .05) activities of aspartate and alanine aminotransferases. Metabolic hormone responses to kochia hay differed in steers vs wethers during undemutrition and mild toxicosis that occurred within 3 wk.
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PMID:Serum constituents and metabolic hormones in sheep and cattle fed Kochia scoparia hay. 188 3

Effects of an 18 min exercise test, on three separate occasions during a one year jump-training programme, was studied in seven horses. Determinations were carried out on venous blood for packed cell volume, haemoglobin, total protein, lactate and pyruvate, glucose, free fatty acids, insulin, glucagon, blood gases, bicarbonate, pH, aldolase, aspartate aminotransferase and alanine amino-transferase. Exercise caused a slight increase in lactate and pyruvate, total protein, aldolase, alanine aminotransferase, pO2, bicarbonate and pH. Glucose, free fatty acids and pCO2 levels decreased. Training caused no significant difference in these changes. However, during the year, increases in lactate and decreases in pH (resting levels) were observed.
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PMID:Changes in some haematological and metabolic indices in young horses during the first year of jump-training. 191 34


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