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)

Kadazans, the largest indigenous group in Sabah, northern Borneo, were surveyed for glyoxalase I, phosphoglucomutase I, red cell acid phosphatase, esterase D, adenosine deaminase, soluble glutamate pyruvate transaminase, soluble glutamate oxaloacetate transaminase, 6-phosphogluconate dehydrogenase, uridine monophosphate kinase, adenylate kinase, peptidase B and D, superoxide dismutase, C5, group specific component, haptoglobin and transferrin. Kadazans were found to be polymorphic for GLO I, PGM I, RCAP, esterase D, ADA, s-Gpt, 6PGD, UMPK, Gc, C5, haptoglobin and peptidase B. Rare variants were found for transferrin and peptidase D. No variant was found for s-Got, SOD and AK.
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PMID:Biochemical genetic markers in the Kadazans of Sabah, Malaysia. 28 26

New biologically active compounds (BAC) created on the basis of nicotinic acid possess hepatoprotective action. The preparations were introduced preventively in doses of 10 mg/kg during 14 days. Litonit and nicogamol increased survival of experimental animals by 36.8% and nicotinic acid by 26.8%. ALT, AST, GGT activity in the blood serum was reduced. The activity of the main antioxidant enzymes (SOD and catalase) grew in the rat liver tissue in parallel with inhibition of DK and MDA activity. Morphological picture of the rat liver, most evident after application of litonit improved. Hepatoprotective action of these BAC are attributed to their membrano stabilizing effects.
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PMID:[Mechanisms of hepatoprotective action of new nicotinic acid derivatives in experimental CCL4-induced liver injury]. 142 11

Using a database of allozyme studies, correlations in heterozygosity between selected enzyme loci (MDH, alpha GPDH, IDH, 6PGDH, LDH, SOD, AAT, PGM, EST, PGI) were calculated across vertebrate species. Large and positive correlations were observed with untransformed heterozygosity values. However, after transformation to correct for mean species heterozygosity, correlations were substantially reduced and median values were closer to zero. Some enzymes were more often involved in significant correlations than others, and correlations calculated across species within vertebrate classes were significant for different enzyme pairs in different classes. There was no evidence that significant correlations occurred primarily between functionally related enzymes. It is suggested that the observed correlations are best explained by variation between enzyme loci in functional constraint and effective neutral mutation rate.
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PMID:A study of interlocus allozyme heterozygosity correlations: implications for neutral theory. 152 53

In order to gain insight into the metabolic modifications induced in rat brain tissues by helium-neon (He-Ne) laser irradiation, in the research described here, we investigated the variations in the activity of the enzymes aspartate transferase (AST, EC 2.6.1.4), both cytosolic and mitochondrial, glutamate dehydrogenase (GIDH, EC 1.4.1.3), and total superoxide dismutase (SOD, EC 1.15.1.1), in the brain of rats treated with a very small dose (1.08 J) of He-Ne laser radiation. The rats were sacrificed 4 h after the treatment. The enzymes were evaluated spectrophotometrically in brain extracts of irradiated animals and also in untreated rats (controls) and rats that underwent simulated treatment (stressed). The data obtained from 5-10 animals assayed individually showed that, in the in toto brain tissues of the irradiated rats compared to the stressed rats, there was a marked increase of total SOD, together with an appreciable decrease of cytosolic AST, and insignificant variations in mitochondrial AST and GIDH. Stress alone caused a considerable decrease of total SOD and small but statistically significant increases of s-AST, m-AST, and GIDH.
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PMID:Rat brain metabolism enzyme activity variations following He-Ne laser irradiation. 177 92

Hepatotoxicity of diethyldithiocarbamate (DDC) was investigated in rats. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were markedly elevated 24 hr after subcutaneous administration of DDC and histologically, the liver showed submassive necrosis. A sustained inhibition in the liver of Cu,Zn-superoxide dismutase (Cu-SOD) activity was observed following DDC treatment. DDC produced a significant loss in liver reduced glutathione (GSH) level after 1 hr, but the nadir was observed later than that of Cu-SOD. Catalase activity decreased gradually from 7 hr. Thiobarbituric acid reactive substances (TBARS) in the liver were significantly increased from 15 hr. Hepatic haemodynamics were scarcely changed up to 15 hr. Desferrioxamine (a chelator of iron) and piperonyl butoxide (an inhibitor of cytochrome P-450) prevented DDC-induced increases of both ALT and TBARS, but GSH did not, DDC hepatotoxicity was not changed by phenobarbital induction. Thus, we have shown that subcutaneous dose of DDC caused hepatotoxicity in rats. Although the exact sequence of its hepatotoxic factors is unproven, it seems likely that lipid peroxidation through the dysfunction of antioxidant defence factors and a toxic metabolite contribute to the formation of this liver injury.
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PMID:Hepatotoxicity of diethyldithiocarbamate in rats. 196 45

The complete amino acid sequence of rat liver cytosolic alanine aminotransferase (EC 2.6.1.2) is presented. Two primary sets of overlapping fragments were obtained by cleavage of the pyridylethylated protein at methionyl and lysyl bonds with cyanogen bromide and Achromobacter protease I, respectively. The protein was found to be acetylated at the amino terminus and contained 495 amino acid residues. The molecular weight of the subunit was calculated to be 55,018 which was in good agreement with a molecular weight of 55,000 determined by SDS-PAGE and also indicated that the active enzyme with a molecular weight of 114,000 was a homodimer composed of two identical subunits. No highly homologous sequence was found in protein sequence databases except for a 20-residue sequence around the pyridoxal 5'-phosphate binding site of the pig heart enzyme [Tanase, S., Kojima, H., & Morino, Y. (1979) Biochemistry 18, 3002-3007], which was almost identical with that of residues 303-322 of the rat liver enzyme. In spite of rather low homology scores, rat alanine aminotransferase is clearly homologous to those of other aminotransferases from the same species, e.g., cytosolic tyrosine aminotransferase (24.7% identity), cytosolic aspartate aminotransferase (17.0%), and mitochondrial aspartate aminotransferase (16.0%). Most of the crucial amino acid residues hydrogen-bonding to pyridoxal 5'-phosphate identified in aspartate aminotransferase by X-ray crystallography are conserved in alanine aminotransferase. This suggests that the topology of secondary structures characteristic in the large domain of other alpha-aminotransferases with known tertiary structure may also be conserved in alanine aminotransferase.
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PMID:Complete amino acid sequence of rat liver cytosolic alanine aminotransferase. 204 42

The import of the precursor of mitochondrial aspartate aminotransferase was reconstituted in vitro with isolated mitochondria thus corroborating the earlier conclusion of a post-translational uptake. The higher Mr precursor was synthesized in a reticulocyte lysate programmed with free polysomes from chicken liver. After incubation with intact mitochondria from chicken heart about 50% of the precursor was converted to the mature form in a time-dependent process, its rate being a function of the amount of mitochondria added. The same amount of precursor was processed to the mature form on addition of a mitochondrial extract. No conversion to the mature enzyme took place when the precursor was incubated with intact mitochondria in the presence of the uncoupling agent carbonyl cyanide m-chlorophenylhydrazone or of the chelator o-phenanthroline which penetrates the mitochondrial inner membrane. In contrast, the chelator bathophenanthroline disulfonate which does not diffuse into the mitochondrial matrix did not inhibit the appearance of the mature form. The results indicate that that precursor must pass through an energized inner mitochondrial membrane before it is processed by a chelator-sensitive protease in the mitochondrial matrix. Excess mature mitochondrial aspartate aminotransferase did not compete with the precursor for its uptake into mitochondria. Mature mitochondrial aspartate aminotransferase is an alpha 2-dimer with Mr = 2 X 45,000. Both the precursor synthesized in a rabbit reticulocyte lysate and the precursor accumulated in the cytosol of carbonyl cyanide m-chlorophenylhydrazone-treated chicken embryo fibroblasts were found to exist as homodimer or hetero-oligomer and high Mr complexes (Mr greater than 300,000).
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PMID:In vitro import into mitochondria of the precursor of mitochondrial aspartate aminotransferase. 394 Oct 76

The most common type of genetic relationship between cytosolic and mitochondrial isoenzymes will probably be found to be divergent evolution from a common ancestral form. This is firmly established for the aspartate aminotransferases and less directly so in other cases. The two isoenzymes of aspartate aminotransferase have evolved at roughly equal rates at the level of total amino acid sequence but certain limited surface regions of the mitochondrial form have been much more highly conserved than corresponding regions in the cytosolic protein; these regions probably play a role in topogenesis of the mitochondrial isoenzyme. It is of interest that nearly all mitochondrial proteins are initially synthesised as precursors of molecular weight greater than the mature forms. In the case of aspartate aminotransferase, and possibly of other such isoenzymes, the N-terminus of the mature protein is nearly coincident with that of the cytosolic isoenzyme. Hence during evolution either the gene for the mitochondrial isoenzyme has gained an extra coding region for this N-terminal extension or, less likely, the structural gene for the cytosolic form has suffered a sizeable terminal deletion. Cytosolic and mitochondrial superoxide dismutases have not shared a common ancestral form as shown by the fact that their primary structures are completely unrelated. On the other hand, the mitochondrial and prokaryotic enzymes are clearly related. There is now, however, evidence to suggest that some prokaryotes possess a copper/zinc enzyme related to the eukaryotic cytosolic form. Hence the possibility arises that primitive prokaryotes possessed both proteins. The copper/zinc superoxide dismutase has been retained in the cytosol of eukaryotic cells and a few bacterial species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structural and genetic relationships between cytosolic and mitochondrial isoenzymes. 639 70

Ornithine decarboxylases from Trypanosoma brucei, mouse, and Leishmania donovani share strict specificity for three basic amino acids, ornithine, lysine, and arginine. To identify residues involved in this substrate specificity and/or in the reaction chemistry, six conserved acidic resides (Asp-88, Glu-94, Asp-233, Glu-274, Asp-361, and Asp-364) were mutated to alanine in the T. brucei enzyme. Each mutation causes a substantial loss in enzyme efficiency. Most notably, mutation of Asp-361 increases the Km for ornithine by 2000-fold, with little effect on kcat, suggesting that this residue is an important substrate binding determinant. Mutation of the only strictly conserved acidic residue, Glu-274, decreases kcat 50-fold; however, substitution of N-methylpyridoxal-5'-phosphate for pyridoxal-5'-phosphate as the cofactor in the reaction restores the kcat of E274A to wild-type levels. These data demonstrate that Glu-274 interacts with the protonated pyridine nitrogen of the cofactor to enhance the electron withdrawing capability of the ring, analogous to Asp-222 in aspartate aminotransferase (Onuffer, J. J., and Kirsch, J. F. (1994) Protein Eng. 7, 413-424). Eukaryotic ornithine decarboxylase is a homodimer with two shared active sites. Residues 88, 94, 233, and 274 are contributed to each active site from the same subunit as Lys-69, while residues 361 and 364 are part of the Cys-360 subunit.
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PMID:Acidic residues important for substrate binding and cofactor reactivity in eukaryotic ornithine decarboxylase identified by alanine scanning mutagenesis. 774 28

Nine populations of Oncomelania, field-collected from Anhui, Shanghai, Jiangsu, Zhejiang, Jiangxi, Hunan, Hubei, Sichuan and Yunnan were studied by horizontal starch gel electrophoretic method with 24 enzyme systems (AAT, AcPH, AK, AO, APH, CK, EST, GDH, GPI, G6PD, HBD, ISDH, LAP, LDH, ME, MDH, MPI, NADD, OCT, PGM, 6PGD, SDH, SOD, XDH) analyzed. 40 loci and 117 alleles were detected in the Oncomelania. Both of GPI and PGM-I, with 7 alleles, were the most variable loci. 22 loci had more than 3 alleles each. Of 40 loci examined in the 24 isozyme systems, 14 were found to be polymorphic, the proportion of multilocus enzymes being 58.3%. Our results showed that the genetic polymorphism existing in the populations of Oncomelania in the mainland of China. PGM and MDH, were found in both the populations of Oncomelania and strains of Schistosoma japonicum in the mainland of China. The results provided a new idea for studying snails and Schistosoma. Also, we found that there might be some correlation between the polymorphic locus and the feature of the shell of Oncomelania snail.
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PMID:[Study on allele frequency in Oncomelania from the mainland of China]. 786 49


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