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 pyridoxal phosphate-dependent enzyme 1-aminocyclopropane-1-carboxylate synthase (ACC synthase; S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14) catalyzes the conversion of S-adenosylmethionine (AdoMet) to ACC and 5'-methylthioadenosine, the committed step in ethylene biosynthesis in plants. Apple ACC synthase was overexpressed in Escherichia coli (3 mg/liter) and purified to near homogeneity. A continuous assay was developed by coupling the ACC synthase reaction to the deamination of 5'-methylthioadenosine by adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) from Aspergillus oryzae. The enzyme is dimeric, with kcat = 9s-1 per monomer and Km = 12 microM for AdoMet. The pyridoxal phosphate-binding site of ACC synthase appears to be highly homologous to that of aspartate aminotransferase, suggesting similar roles for corresponding residues. Site-directed mutagenesis of Lys-273, Arg-407, and Tyr-233 (corresponding to residues 258, 386, and 225 in aspartate aminotransferase) and kinetic analyses of the mutants confirms their importance in the ACC synthase mechanism. The Lys-273 to Ala mutant has no detectable activity, supporting the identification of this residue as the base catalyzing C alpha proton abstraction. Mutation of Arg-407 to Lys results in a precipitous drop in kcat/Km and an increase in Km for AdoMet of at least 20-fold, in accordance with its proposed role as principal ligand for the substrate alpha-carboxylate group. Replacement of Tyr-233 with Phe causes a 24-fold increase in the Km for AdoMet and no change in kcat, suggesting that this residue plays a role in orienting the pyridoxal phosphate cofactor in the active site.
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PMID:Expression of apple 1-aminocyclopropane-1-carboxylate synthase in Escherichia coli: kinetic characterization of wild-type and active-site mutant forms. 780 54

The gene organization of a 7.4-kb region of the Streptomyces virginiae (Sv) chromosome was determined. The predicted open reading frames (ORFs) and their predicted products, in sequence order, were (i) ada, encoding adenosine deaminase [EC 3.5.4.4], (ii) aat, encoding a protein homologous to aspartate aminotransferase [EC 2.6.1.1], (iii) secE, encoding a protein involved in protein secretion, (iv) vbrA, encoding a NusG-like protein involved in antitermination of transcription as described by Okamoto et al. [J. Biol. Chem. 267 (1992) 1093-1098], and (v) rplKAJL, encoding the large subunits of the ribosomal proteins L11, L1, L10 and L12. Six of the ORFs (secE-rplL) were oriented in the same direction, but the other two (ada and aat) had the opposite orientation. The gene organization of the secE-rplL region in Sv was identical to that in Escherichia coli.
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PMID:Gene organization in the ada-rplL region of Streptomyces virginiae. 867 24

Serum Adenosine deaminase (ADA) activity in normal healthy control subjects increases upto 30 years, remains steady between 31-60 years of age and shows a steep increase in the age group of 61-70 years. This was compared with serum aspartate transaminase (AST) and alanine transaminase (ALT) activity which also showed a gradual increase upto 40 years of age and decreased thereafter. The activities of serum ADA, AST and ALT increased in patients with hepatitis of all age groups compared to their respective controls. The degree of increase in the activities of the above enzymes in hepatitis, decreased with age. The present study also shows that while studying serum ADA activity in hepatitis for diagnostic purposes, the value obtained in a particular age group should be compared with normal range of values for the respective age group only.
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PMID:Studies on the age dependent changes in serum adenosine deaminase activity and its changes in hepatitis. 2310 81

A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p=0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.
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PMID:Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia. 2706 84