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)

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)
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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

Aspartate aminotransferase from the archaebacterium Haloferax mediterranei was purified and found to be homogeneous. An average Mr of 66,000 was estimated. The native halophilic transaminase exhibited no maximum absorption at 410 nm, which indicates that the apo form is obtained by our purification procedure, and the molar absorption coefficient at 275 nm in 3.5 M-KCl (pH 7.8) was found to be 78.34 mM-1.cm-1. Plots of titration data show that 1 mol of halophilic aspartate aminotransferase binds 2 mol of pyridoxal 5'-phosphate. The halophilic transaminase behaved as a dimer with two similar subunits and had a maximum activity in the pH range 7.6-7.9 and at 65 degrees C in 3.5 M-KCl. By differential scanning calorimetry, the denaturation temperature of the halophilic holo- and apo-transaminase was determined to be 78.5 and 68.0 degrees C respectively at 3.3 M-KCl (pH 7.8). At low salt concentration the halophilic transaminase was inactivated, following first-order kinetics. The Km values for 2-oxoglutarate and L-aspartate, in 3 M-KCl (pH 7.8), were 0.75 mM and 12.6 mM respectively.
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PMID:Purification and characterization of aspartate aminotransferase from the halophile archaebacterium Haloferax mediterranei. 190 12

Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.
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PMID:Prognosis of Wilsonian chronic active hepatitis. 199 98

Male and female Sprague-Dawley rats were administered the sodium salt of monochloroacetic acid (SMCA) by oral gavage for a period of 90 consecutive days. Dosage levels of 15, 30, 60 or 120 mg/kg per day were employed. SMCA clearly induced toxicity in both females and males, with the greatest severity in the male animals. Both the liver and kidneys were identified as target organs. At 120 mg/kg per day, 30% of females and 80% of the males died, most within the first 2 days of treatment. Hemorrhagic and congested lungs (possibly a postmortem change) were seen in the early deaths (1-3 days) whereas liver lesions were observed in later deaths. In addition, there was nephrotoxicity as evidenced by elevated creatinine, blood calcium (BCAL), and blood urea nitrogen (BUN) levels. Hepatotoxicity was indicated by increases in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both organs showed increased organ-to-body weight ratios. Microscopic examination revealed a significant (P less than or equal to 0.001) increase in chronic renal nephropathy and increased splenic pigmentation at 60 mg/kg per day in the males. Based on the observation of toxicity at all treatment levels in males, a lowest observed adverse effect level (LOAEL) of 15 mg/kg per day is proposed for a 90-day exposure to SMCA by oral gavage to the Sprague--Dawley rat.
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PMID:Ninety-day toxicity study of sodium monochloroacetate in Sprague-Dawley rats. 203 Dec 51

A reinvestigation of the effects of pH and salt concentration on the proton and dicarboxylic acid dissociation constants of pig heart aspartate aminotransferase shows that both anions and cations were involved concomitantly, both as stoichiometric reactants and bioenergetically. Equations are presented which can be used experimentally, to determine the numbers of salt ions (their thermodynamic stoichiometries) involved in biochemical equilibria such as proton and ligand dissociations from macromolecules. These equations were used to reinvestigate the effects of salts on the chromophoric pKa of the enzyme prosthetic group, the interaction of the enzyme with dicarboxylic acids, and the overall equilibrium for the transamination half-reaction.
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PMID:Thermodynamic bookkeeping: a reinvestigation of proton and dicarboxylic acid binding to aspartate aminotransferase. 254 52

Sodium valproate (VPA), the salt of a branched short-chain fatty acid, is a major antiepileptic whose mode of action, as yet unclear, may involve effects on the organization of membranes. VPA was either injected into rats whose liver and kidney mitochondria were then isolated, or was preincubated with isolated mitochondria. First, liver and kidney mitochondria were studied with paramagnetic probes. The electron paramagnetic resonance spectra of proteins of VPA-treated mitochondria spin-labeled with 4-maleimido-2,2,6,6-tetramethyl-1-pyrrolidinoxyl showed that the ratio of weakly immobilized to strongly immobilized SH groups was reduced with respect to control mitochondria, more so in liver than in kidney mitochondria of VPA-injected rats, and more so in kidney than in liver mitochondria for VPA-incubated mitochondria. Spectra of mitochondrial lipids spin-labeled with 5-doxyl stearic methyl ester showed that VPA had no significant effect on order parameters S. Second, the transmembrane movement of aspartate aminotransferase was studied by incubating liver mitochondria in a sucrose-succinate medium and then fractionating them. The translocation of aspartate aminotransferase from mitoplasts, vesicles formed of inner membrane and matrix, to the intermembrane fluid, was significantly higher in VPA-treated than in control mitochondria. Thus, VPA, at concentrations in the range of those used therapeutically, interacted with membranes by modifying the structural organization of the internal mitochondrial membrane, essentially the membrane protein conformation.
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PMID:Effects of sodium valproate on mitochondrial membranes: electron paramagnetic resonance and transmembrane protein movement studies. 301 82

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)
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PMID:Role of arginine-292 in the substrate specificity of aspartate aminotransferase as examined by site-directed mutagenesis. 316

A lead-salt procedure was used for the cytochemical demonstration of aspartate aminotransferase (AT) in the CA3 of the rat hippocampus. Cytoplasmic- and mitochondrial-AT isoenzymes were demonstrated in different neuronal structures, but not in astrocytes. Of special interest was the localization of cytoplasmic AT in most mossy-fibre boutons. This might indicate that cytoplasmic AT is responsible for the production of releasable glutamate in the glutamatergic/aspartatergic mossy fibre system.
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PMID:Cytochemical demonstration of aspartate aminotransferase in the mossy-fibre system of the rat hippocampus. 369 29

beta-Sulfopyruvic acid (2-carboxy-2-oxoethanesulfonic acid) is prepared in greater than 90% yield by reaction of bromopyruvic acid with sodium sulfite. beta-[35S]Sulfopyruvate is prepared by transamination between [35S]cysteinesulfonate (cysteate) and alpha-ketoglutarate using mitochondrial aspartate aminotransferase isolated from rat liver. Following either chemical or enzymatic synthesis, the crude reaction product is conveniently purified by chromatography on Dowex 1; beta-sulfopyruvate is isolated as the stable, water-soluble dilithium salt. beta-Sulfopyruvate is shown to be an alternative substrate of mitochondrial malate dehydrogenase; in the presence of 0.25 mM NADH, beta-sulfopyruvate is reduced with an apparent Km of 6.3 mM and a Vmax equal to about 40% of that observed with oxaloacetate. This finding forms the basis of a convenient spectrophotometric assay of beta-sulfopyruvate.
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PMID:beta-Sulfopyruvate: chemical and enzymatic syntheses and enzymatic assay. 374 Apr 6

It was recently suggested that the apparent biliary transport maximum (Tm, secretory maximum) for bile salts is primarily determined by their degree of cytotoxicity (the cytotoxicity hypothesis), based on experiments on male rats [Hardison, W. G., D. E. Hatoff, K. Miyai, and R. G. Weiner. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G337-G343, 1981]. To confirm this hypothesis, we determined the Tm of three different bile salts, taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC) in female rats and hamsters. The order of Tm values in female rats was the same as that reported for male rats (TUDC greater than TC greater than TCDC), whereas in female hamsters it was TC greater than TCDC greater than TUDC. On the other hand, in hamsters, the order of cytotoxicity, evaluated in vivo by the biliary excretion of hepatocyte enzymes such as lactate dehydrogenase and alkaline-phosphatase and an increase in plasma lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase levels under a fixed rate infusion (0.6 and 1.2 mumol X min-1 X 100 g body wt-1) of bile salts, was inverse to the order of Tm values (TCDC greater than TC greater than TUDC) in rats, but in hamsters, too, TCDC was most cytotoxic. The order of Tm value in hamsters thus does not correspond to the order of cytotoxicity of these bile salts, suggesting that the cytotoxicity of bile salts may not be the sole determinant of bile salt Tm.
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PMID:Differing transport maxima values for taurine-conjugated bile salts in rats and hamsters. 378 51


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