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)

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.
J Biol Chem 1991 Sep 15
PMID:NMR observation of exchangeable protons of pyridoxal phosphate and histidine residues in cytosolic aspartate aminotransferase. 165 26

Recent studies indicate that in animals with marked cardiac hypertrophy, there is depressed function of Ca2+ sequestration by myocardial sarcoplasmic reticulum (SR) because of down regulation of the Ca(2+)-ATPase gene. However, in several animal models we have observed enhancement of myocardial Ca2+ sequestration in response to chronic cardiac stimulation. We tested the hypothesis that in animals with mild cardiac hypertrophy, there is enhanced Ca(2+)-cycling activity by the SR Ca2+ pump and Ca(2+)-release channel. Because creatine kinase activity is consistently decreased in cardiomyopathy, we also determined whether enhanced Ca2+ cycling was accompanied by down regulation or inhibition of the creatine kinase system. Mild cardiac hypertrophy was induced by volume overload; 2% salt was added to the diet of 2-week-old turkey poults for 4 weeks. Compared with age-matched controls, volume overload resulted in 14.3% increase in heart weight and 21.5% increase in heart-to-body weight ratios. The hypertrophied heart had approximately 20% increased activities of the SR Ca2+ pump and the SR Ca2+ channel. Net Ca2+ transport was increased by 16.5%. Compared with controls and in contrast to several other myocardial enzymes, creatine kinase activity was diminished in the hypertrophied hearts by 23% and creatine content was decreased by 8%. Differences between groups were not detected for lactate dehydrogenase, aspartate transaminase, and alanine transaminase. We concluded that an early adaptation of the myocardium undergoing hypertrophy in compensatory response to functional overload is an enhancement of Ca2+ cycling activity by the Ca2+ pump and Ca2+ channel of the SR.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Vet Res 1991 Sep
PMID:Effects of mild cardiac hypertrophy, induced by volume overload in turkeys, on myocardial sarcoplasmic reticulum calcium-pump and calcium-channel activities and on the creatine kinase system. 165 61

The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH) and isocitric dehydrogenase (ICD) in the serum of 60 healthy dromedary camels of either sex and different ages (one to 25 years) were determined. The results were analysed with respect to time of year (December-January and May-June), sex and age groups (below four years; four to 10 years; and over 10 years). The overall mean activities of AST, ALT, ALP, ACP, LDH and ICD were 36.1 +/- 0.35, 4.65 +/- 0.35, 27.21 +/- 0.43, 7.18 +/- 0.21, 479.0 +/- 7.33 and 7.74 +/- 0.17 iu litre-1, respectively. Activities of AST, ALT, ALP and ACP were significantly higher during extremely hot conditions (May-June) than in extreme cold (December-January) while the activity of LDH was higher in extremely cold conditions. Analysis of data based on sex revealed that AST, ALT and ALP activities in the serum of male animals were significantly higher than in female animals. The activities of all the enzymes were highest in animals under four years and then gradually decreased with age being lowest in the animals over 10 years.
Res Vet Sci 1991 Sep
PMID:Activity of some enzymes in the serum of dromedary camels. 166 69

Applying catalytic enzyme histochemistry, glutamate dehydrogenase (GDH) and phosphate activated glutaminase (PAG) were demonstrated at the light microscopic level, and aspartate aminotransferase (AAT) was detected at the electron microscopic level. GDH staining appeared preferentially in glial cells (Bergmann glia and astrocytes), whereas AAT was localized only in neuronal structures. Cytoplasmic AAT was demonstrated in the perikarya and terminal plexus of basket cells, in the perikarya of stellate cells, in about 60% of the granule cells, in mossy fiber boutons, in numerous small boutons in the molecular layer, and in the axoplasm of numerous myelinated and unmyelinated fibers. PAG was observed in both neuronal structures (perikarya of granule and Purkinje cells) and in astrocytes and Bergmann glia.
Neurosci Lett 1991 Sep 16
PMID:Histochemistry of glutamate metabolizing enzymes in the rat cerebellar cortex. 168 39

The inability of the 'ethanol/high vitamin A Lieber-DeCarli diet' to induce liver fibrosis in two different rat strains was further evaluated by determining changes in parameters of liver cell damage and of retinoid and lipid metabolism. In the ethanol/vitamin A-treated group, slight but constant hepatic cell damage, as indicated by elevated alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities in blood, was already observed at 6 months and maintained until the time of death at 16 months. Serum gamma-glutamyl transaminase activities were not raised. Moderate parenchymal liver cell damage was not accompanied by fibrosis. Hypertriglyceridemia or hypercholesterolemia were observed at 6-16 months of chronic alcohol administration. This response was strain dependent. In ethanol-treated rats of both strains, total liver retinoids and serum retinol concentrations were not altered. Therefore, the hypothesis that interaction between alcohol and retinoids is a major factor in the pathogenesis of alcoholic liver disease, needs to be reconsidered.
J Hepatol 1991 Sep
PMID:Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 2. Biochemical observations. 174 28

The relationship between the amount of exercise-induced muscle damage and the release of creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LD) was studied. Gender differences in enzyme release and histological damage were also studied. Serial pre- and postexercise blood samples were drawn from untrained male and female catheterized Wistar rats that ran 1.5 or 2.5 h on a treadmill (incline 10 degrees). Three days postexercise, muscle damage was quantified morphometrically in five different hindlimb and forearm muscles. The 1.5 and 2.5 h of exercise elicited histological damage only in the soleus muscle. Significant plasma CK, AST, and LD elevations were found immediately postexercise both in male and female rats. However, the enzyme release was significantly greater in males than in females. Part of this could be explained by differences in clearance rates between males and females. No gender difference in amount of histological damage was found. The actual volume of histological muscle damage was significantly less than the calculated muscle damage based on enzyme release. An increase in the exercise duration from 1.5 to 2.5 h resulted in a disproportional increase in both histological muscle damage and muscle enzyme release. From the present study it is concluded that muscle enzyme release is not clearly reflected in histological muscle damage.
J Appl Physiol (1985) 1991 Sep
PMID:Relationship between exercise-induced muscle damage and enzyme release in rats. 175 39

Two trials were conducted to determine the effect of monensin in broiler litter on sheep receiving the broiler litter in their diets. Broiler litter from chickens fed monensin as a coccidiostat, and from chickens receiving no coccidiostat, was included at a level of 30% in 2 sheep diets. In a further 2 treatments, monensin (15 mg kg-1) was added to each of the 2 diets to give a 2x2 factorial experimental design. In the first trial, copper (20 mg kg-1 feed) was added to the diets. These lambs were fed individually at a slightly restricted level of intake. No differences between treatments were observed in feed intake, average daily gain or efficiency of feed utilisation or in the concentrations of zinc, iron and manganese in the liver, glutathione peroxidase in erythrocytes and creatine kinase concentrations in the plasma. Hepatic copper content and copper retention in the livers of the sheep receiving the added monensin were significantly higher (P less than 0.05 and less than 0.01 respectively) than in those not receiving added monensin. The aspartate transaminase and alkaline phosphatase concentrations in the plasma of these sheep were also higher (P less than 0.05) than in those not consuming added monensin. In the second trial, the lambs were group-fed according to treatment and received the diets on an ad lib basis. The mean intakes of the groups receiving the diets with the added monensin, were lower than the intakes by the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
J S Afr Vet Assoc 1991 Sep
PMID:Effect of monensin and its metabolites in broiler litter on sheep consuming the broiler litter. 177 Apr 87

This study was concerned with the role of Cu and Cu-MT (metallothionein) in oxidative stress. Because hepatic Cu and Cu-MT concentrations are known to be high in the 3-day-old guinea pigs but decline to low adult levels by 7 days of life, the hepatotoxicity of ferric nitrilotriacetate (FeNTA) in the developing guinea pig was used as the experimental model in the present study. Results of this study showed that the hepatotoxic response to FeNTA (3.5 mg Fe /kg i.p.) as measured by elevation in serum aspartate aminotransferase activity, increase in lipid peroxidation, decrease in reduced glutathione/oxidized glutathione ratio and histopathological changes was higher in 3-day-old than in 7-day-old and adult guinea pigs. Furthermore, pretreatment of 7-day-old guinea pigs with cupric sulfate (0.5 mg Cu++/kg i.p.) increased hepatic Cu and Cu-MT levels and enhanced susceptibility to FeNTA. FeNTA treatment resulted in the oxidation of MT thiolates and reduction in the metal binding capacity and Cu content of MT in the 3-day-old and Cu-pretreated 7-day-old animals, providing evidence for the interaction between Cu-MT and cellular oxidants. In vitro study with FeNTA and hepatic microsomes revealed no age-related differences in microsomal lipid peroxidation; however, this parameter was stimulated in the presence of control or heat-treated cytosols isolated from 3-day-old but not those of 7-day-old animals. These observations were consistent with the involvement of Cu-MT, a heat-stable metalloprotein, in the sensitization of hepatic tissues to oxidative injury in the 3-day-old animal. Moreover, in vitro study involving the use of D-penicillamine, a Cu chelating agent, showed that the sensitization effect of Cu-MT was mediated by Cu ions. The results of this study suggest that Cu-MT may have a prooxidative property and tissues with high Cu-MT levels may be particularly susceptible to oxidative stress.
J Pharmacol Exp Ther 1991 Sep
PMID:Age-related differences in iron-nitrilotriacetate hepatotoxicity in the guinea pig: role of copper metallothionein. 189 Jun 21

Twenty-five transhepatic embolization procedures were carried out between 1984 and 1989 on 24 patients with life-threatening haemorrhage from gastric or oesophageal varices after conservative methods had failed. There were two deaths related to the procedure and another 17 patients died during the following year. There were five survivors at 1 year, four are alive and well 4 years later, the fifth was lost to follow-up at 2 1/2 years. Survival at 1 year was not affected by a number of factors present at the time of embolization including the underlying liver pathology, the patient's age, platelet count, blood urea, serum bilirubin or the embolization technique. However, survival at 1 year was related to more normal coagulation values (international normalized ratios, INR) P less than 0.005, normal serum aspartate aminotransferase levels (P less than 0.025) and Pugh's grade A (P less than 0.01). We conclude that this procedure can prolong the survival of a small proportion of good risk patients.
Clin Radiol 1991 Sep
PMID:Survival after transhepatic embolization of gastro-oesophageal varices. 191 94

Four new crystal forms of chicken cytosolic aspartate aminotransferase have been grown from polyethylene glycol solutions. Crystals of the unliganded enzyme and of enzyme liganded with maleate diffract to 1.8 A resolution. Both the free and maleate-liganded enzymes crystallize in space group P2(1)2(1)2(1), but display slightly different cell dimensions (a = 56.9 A, b = 126.9 A and c = 124.6 A versus a = 56.5 A, b = 126.1 A and c = 124.6 A). The influence of various divalent metal ions, dioxane and non-ionic detergent beta-octylglucoside on crystallization has been investigated. The best crystals of liganded enzyme were obtained in the presence of Mg2+ ions, and these crystals were used for data collection to 1.9 A resolution.
J Mol Biol 1991 Sep 05
PMID:New crystal form of cytosolic chicken aspartate aminotransferase suitable for high-resolution X-ray analysis. 192 Apr 19


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