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

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

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

The influence of Z-4,4-bis(4-ethylphenyl)-2,3-dibromo-2-butenoic acid, the compound originally synthetized as a cytostatic edikron and showing inhibitory effect on several pyridoxal enzymes, on absorption and circular dichroism spectra of alanine and aspartate aminotransferases (ALT, AST) in the region of coenzyme absorption characteristics was studied. In the case of AST, the compound decreased absorption and CD maxima at 360 nm, which represents the active form of the enzyme, but it did not seem to prevent formation of the pyridoxamine form of the enzyme, produced in the presence of L-aspartate. Edikron caused insignificant spectral changes of ALT, but it partially denatured the enzyme. Circular dichroism measurement of both enzymes uncovered some effects of edikron at 250-300 nm, which suggests conformational changes in the aromatic amino acids of the apoenzymes due to the compound studied.
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PMID:Interaction of Z-4,4-bis(4-ethylphenyl)-2,3-dibromo-2-butenoic acid with aminotransferases: changes in absorption and circular dichroism spectra. 182 79

The influence of repeated s.c. administration of the cytostatic 5-[2-(N,N-dimethylamino)ethoxy]-7-oxo-7H-benzo(c)fluorene hydrochloride (benflurone, 25 mg/kg body weight daily) on the activities of aspartate and alanine aminotransferases (AST, ALT) per g of tissue, and protein concentration in the liver of adult male rats was studied. During the first week of benflurone administration, the activities of ALT and AST decreased by 2/3 and 1/3, respectively, in comparison with controls while the protein concentration did not show any substantial change. No in vitro influence of benflurone on AST and ALT was found even at the highest concentration tested (10(-4) M). The significance of the aminotransferase decrease after treatment with benflurone and possible participation of these changes in the side- or cytostatic effects of the compound are considered.
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PMID:Influence of 5-[2-(N,N-dimethylamino)ethoxy]-7-oxo-7H-benzo(C)fluorene hydrochloride (benflurone) on the activity of rat liver aspartate and alanine aminotransferases. 182 83

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

Aspartate aminotransferase from the archaebacterium Sulfolobus solfataricus binds pyridoxal 5' phosphate, via an aldimine bond, with Lys-241. This residue has been identified by reducing the enzyme in the pyridoxal form with sodium cyanoboro[3H]hydride and sequencing the specifically labeled peptic peptides. The amino acid sequence centered around the coenzyme binding site is highly conserved between thermophilic aspartate aminotransferases and differs from that found in mesophilic isoenzymes. An alignment of aspartate aminotransferase from Sulfolobus solfataricus with mesophilic isoenzymes, attempted in spite of the low degree of similarity, was confirmed by the correspondence between pyridoxal 5' phosphate binding residues. Using this alignment it was possible to insert the archaebacterial aspartate aminotransferase into a subclass, subclass I, of pyridoxal 5' phosphate binding enzymes comprising mesophilic aspartate aminotransferases, tyrosine aminotransferases and histidinol phosphate aminotransferases. These enzymes share 12 invariant amino acids most of which interact with the coenzyme or with the substrates. Some enzymes of subclass I and in particular aspartate aminotransferase from Sulfolobus solfataricus, lack a positively charged residue, corresponding to Arg-292, which in pig cytosolic aspartate aminotransferase interacts with the distal carboxylate of the substrates (and determines the specificity towards dicarboxylic acids). It was confirmed that aspartate aminotransferase from Sulfolobus solfataricus does not possess any arginine residue exposed to chemical modifications responsible for the binding of omega-carboxylate of the substrates. Furthermore, it has been found that aspartate aminotransferase from Sulfolobus solfataricus is fairly active when alanine is used as substrate and that this activity is not affected by the presence of formate. The KM value of the thermophilic aspartate aminotransferase towards alanine is at least one order of magnitude lower than that of the mesophilic analogue enzymes.
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PMID:The active site of Sulfolobus solfataricus aspartate aminotransferase. 195 27


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