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 complete amino acid sequence of the mitochondrial aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) from human heart has been determined based mainly on analysis of peptides obtained by digestion with trypsin and by chemical cleavage with cyanogen bromide. Comparison of the sequence with those of the isotopic isoenzymes from pig, rat and chicken showed 27, 29 and 55 differences, respectively, out of a total of 401 amino acid residues. Evidence for structural microheterogeneity at position 317 has also been obtained.
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PMID:The primary structure of mitochondrial aspartate aminotransferase from human heart. 405 35

The amino acid sequence of aspartate aminotransferase from E. coli B was determined by the alignment of seven cyanogen bromide peptides. The established sequence of the subunit was composed of 396 amino acid residues, and the molecular weight was calculated to be 43,573. The sequence was compared with those of the pig cytoplasmic and mitochondrial isoenzymes, showing that nearly 30% of all residues were invariant and that the E. coli enzyme exhibited the same degree of homology (about 40%) with either of them. Although majority of the residues were substituted, the functional residues constituting the active site structure were conserved.
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PMID:The complete amino acid sequence of aspartate aminotransferase from Escherichia coli: sequence comparison with pig isoenzymes. 637 5

Inactivation of the beta 2 subunit and of the alpha 2 beta 2 complex of tryptophan synthase of Escherichia coli by the arginine-specific dicarbonyl reagent phenylglyoxal results from modification of one arginyl residue per beta monomer. The substrate L-serine protects the holo beta 2 subunit and the holo alpha 2 beta 2 complex from both inactivation and arginine modification but has no effect on the inactivation or modification of the apo forms of the enzyme. This result and the finding that phenylglyoxal competes with L-serine in reactions catalyzed by both the holo beta 2 subunit and the holo alpha 2 beta 2 complex indicate that L-serine and phenylglyoxal both bind to the same essential arginyl residue in the holo beta 2 subunit. The apo beta 2 subunit is protected from phenylglyoxal inactivation much more effectively by phosphopyridoxyl-L-serine than by either pyridoxal phosphate or pyridoxine phosphate, both of which lack the L-serine moiety. The phenylglyoxal-modified apo beta 2 subunit binds pyridoxal phosphate and the alpha subunit but cannot bind L-serine or L-tryptophan. We conclude that the alpha-carboxyl group of L-serine and not the phosphate of pyridoxal phosphate binds to the essential arginyl residue in the beta 2 subunit. The specific arginyl residue in the beta 2 subunit which is protected by L-serine from modification by phenyl[2-14C]glyoxal has been identified as arginine-148 by isolating a labeled cyanogen bromide fragment (residues 135-149) and by digesting this fragment with pepsin to yield the labeled dipeptide arginine-methionine (residues 148-149). The primary sequence near arginine-148 contains three other basic residues (lysine-137, arginine-141, and arginine-150) which may facilitate anion binding and increase the reactivity of arginine-148. The conservation of the arginine residues 141, 148, and 150 in the sequences of tryptophan synthase from E. coli, Salmonella typhimurium, and yeast supports a functional role for these three residues in anion binding. The location and role of the active-site arginyl residues in the beta 2 subunit and in two other enzymes which contain pyridoxal phosphate, aspartate aminotransferase and glycogen phosphorylase, are compared.
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PMID:L-serine binds to arginine-148 of the beta 2 subunit of Escherichia coli tryptophan synthase. 641 46

Twelve cyanogen bromide peptides were isolated from S-carboxymethylated mitochondrial aspartate aminotransferase and their amino acid sequences were determined. These peptides were purified first by gel filtration on a Sephadex G-75 column, and then by gel filtration on Bio-Gel, or by ion exchange chromatography on a phosphocellulose column in the presence of 8 M urea, or by both methods. Small peptides were purified by paper chromatography. The cyanogen bromide peptides accounted for 367 of the 401 amino acid residues in the subunit of the enzyme. No peptide accounting for the other 34 residues was obtained in a homogeneous state, but peptide mixtures containing this particular peptide were analyzed by various procedures including Edman degradation and digestion with Staphylococcus aureus protease. The results accounted for all 401 amino acid residues.
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PMID:Complete amino acid sequence of mitochondrial aspartate aminotransferase from pig heart muscle. Cyanogen bromide peptides. 739 Oct 11

Amino-acid sequence of kynureninase purified from rat liver cytosol was determined by an amino-acid sequencer. The enzyme was degraded to small peptides with cyanogen bromide, TPCK-trypsin, endoproteinase Glu-C, lysyl endoprotease and alpha-chymotrypsin. The enzyme subunit consisted of 464 amino acids, and the molecular weight of subunit was determined to be 52,510. The coenzyme pyridoxal phosphate-binding residue was lysine of which position was 276, and the N-terminal residue was N-acetylmethionine. The homology search between this enzyme and the other pyridoxal phosphate-dependent enzymes showed that kynureninase was similar to mitochondrial aspartate aminotransferase, and also to cystathionine gamma-synthase and gamma-lyase to a lesser extent.
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PMID:Amino-acid sequence of rat liver kynureninase. 757 21

The protective effect of N-(2-mercaptopropionyl)-glycine (tiopronin), a clinically used sulfhydryl-containing compound, on cisplatin-induced toxicity to rat renal cortical slices was investigated. Exposure of the slices to cisplatin (2 mM) resulted in toxicity, as shown by an increase in leakage of the two enzymes aspartate aminotransferase and lactate dehydrogenase into the incubation medium and a time-dependent decrease in the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by the slices. Tiopronin (2 mM) completely prevented the cisplatin-induced increase in enzyme leakage and substantially blocked the decrease of MTT reduction caused by cisplatin. These protective effects were concentration-dependent and furthermore, the depletion of ATP, glutathione and induction of lipid peroxidation in the slices by cisplatin (2 mM) were reversed by 2 mM tiopronin. Pretreatment of slices with tiopronin for 60 min also significantly protected the renal slices from cisplatin-induced toxic effects. These protective effects, however, were abolished by p-aminohippuric acid, a compound with some structural similarity to tiopronin, which both undergoes and inhibits active transport in the cells of the proximal convoluted tubule. Cisplatin (1 mM) also depleted the free sulfhydryls of tiopronin (1 mM) in a second incubation medium system and PAH (2 mM) diminished the extent of this depletion somewhat. These observations suggest that tiopronin protects against cisplatin-induced nephrotoxicity by acting as an alternative target for cisplatin both intra- and extracellularly and thus protects against cisplatin-induced depletion of glutathione in the kidney cell.
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PMID:Tiopronin protects against the nephrotoxicity of cisplatin in rat renal cortical slices in vitro. 897 67

The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.
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PMID:Ethionine toxicity in vitro: the correlation of data from rat hepatocyte suspensions and monolayers with in vivo observations. 980 31

Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/day, 3 times/wk for 4 to 8 wk. Creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum (hemisphere and vermis) and largest in the brainstem (hypothalamus, midbrain, and medulla oblongata). The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose (290 to 495 ppm) or on prolonging exposure period (4 to 8 wk). Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.
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PMID:Inhibition of creatine kinase activity in rat brain by methyl bromide gas. 1149 99

We examined the effect of dietary conjugated linoleic acid (CLA) on liver regeneration after a partial hepatectomy (PH) in Sprague-Dawley rats. PH was performed on rats fed a 0 or 1 wt.% CLA diet for 3 wk. Average liver weight in the CLA fed rat population was heavier than the control rat population at the time of PH and 1-d after PH. Conversely. CLA fed rats' liver weight was significantly lower than control rats at 7-d after PH. This suggests that dietary CLA reduced liver weight gain after PH. Dietary CLA did not affect serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) activities. However. CLA significantly reduced serum albumin levels at 1-d but not at 7-d after PH. 5-Bromo- and 5-iododeoxyuridine incorporation into hepatocytes 1-d post PH was lower in the CLA group. In conclusion, the data suggests that dietary CLA inhibits DNA synthesis after PH, which results in hepatocyte proliferation inhibition.
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PMID:Effect of dietary conjugated linoleic acid on liver regeneration after a partial hepatectomy in rats. 1522 11

Kava (Piper methysticum), a perennial shrub native to the South Pacific islands, has been used to relieve anxiety. Recently, several cases of severe hepatotoxicity have been reported from the consumption of dietary supplements containing kava. It is unclear whether the kava constituents, kavalactones, are responsible for the associated hepatotoxicity. To investigate the key components responsible for the liver toxicity, bioassay-guided fractionation was carried out in this study. Kava roots, leaves, and stem peelings were extracted with methanol, and the resulting residues were subjected to partition with a different polarity of solvents (hexane, ethyl acetate, n-butanol, and water) for evaluation of their cytotoxicity on HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase and aspartate aminotransferase enzyme leakage assays. Organic solvent fractions displayed a much stronger cytotoxicity than water fractions for all parts of kava. The hexane fraction of the root exhibited stronger cytotoxic effects than fractions of root extracted with other solvents or extracts from the other parts of kava. Further investigations using bioassay-directed isolation and analysis of the hexane fraction indicated that the compound responsible for the cytotoxicity was flavokavain B. The identity of the compound was confirmed by (1)H and (13) C NMR and MS techniques.
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PMID:In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum). 1660 46


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