Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5'-Methylthioadenosine (MTA) produced during the synthesis of polyamines is degraded to adenine by MTA phosphorylase. This pathway is considered to be the main source of endogenous adenine. We determined the concentrations of MTA and adenine in control subjects and in those with a pathological disorder. In patients with active leukemias, as well as with other types of malignancies, the concentrations of MTA and adenine in the urine were elevated. These changes seemed to be the result of an accelerated production of MTA due to an accelerated biosynthesis of polyamine. In patients with adenine phosphoribosyltransferase (APRT) deficiency, the concentrations of adenine in the urine were elevated, presumably due to a disturbance in the catabolism of adenine. Although adenine is a potent inhibitor of MTA phosphorylase, APRT-deficient patients did not excrete MTA into urine in concentrations significantly larger than noted for control subjects. However, the amount of MTA excreted positively correlated with that of adenine in these patients, hence that accumulated adenine probably had a slight, but positive, inhibitory effect on the degradation of MTA.
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PMID:Disturbance in the metabolism of 5'-methylthioadenosine and adenine in patients with neoplastic diseases, and in those with a deficiency in adenine phosphoribosyltransferase. 189 56

1. Activities of the following enzymes involved in adenine and adenosine metabolism were found in cell-free extracts from Euglena gracilis: acid phosphatase (EC 3.1.3.2), 5'-methylthioadenosine phosphorylase (EC 2.4.2.-), adenine deaminase (EC 3.5.4.2), adenine phosphoribosyltransferase (EC 2.4.2.7) and adenosine kinase (EC 2.7.1.20). 2. The activities occurred both in heterotrophic and photoautotrophic cells and their levels did not change during light-induced chloroplast development. 3. Neither S-adenosylhomocysteinase (EC 3.3.1.1), 5'-methylthioadenosine nucleosidase (EC 3.2.2.9) and nucleoside phosphotransferase (EC 2.7.1.77) nor adenosine degrading enzymes: adenosine deaminase (EC 3.5.4.4), adenosine nucleosidase (EC 3.2.2.7), and purine-nucleoside (adenosine) phosphorylase (EC 2.4.2.1) were found in the Euglena extracts. 4. Comparison of the adenine and adenosine metabolism in Euglena and in other organisms is comprehensively presented. The metabolism in Euglena gracilis differs from that in higher animals and plants.
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PMID:Adenine and adenosine metabolizing enzymes in cell-free extracts from Euglena gracilis. 680 64

5'-Methylthioadenosine phosphorylase (MTAP) and 5'-methylthioadenosine nucleosidase (MTAN) catalyze the phosphorolysis and hydrolysis of 5'-methylthioadenosine (MTA), respectively. Both enzymes have low KM values for their substrates. Kinetic assays for these enzymes are challenging, as the ultraviolet absorbance spectra for reactant MTA and product adenine are similar. We report a new assay using 2-amino-5'-methylthioadenosine (2AMTA) as an alternative substrate for MTAP and MTAN enzymes. Hydrolysis or phosphorolysis of 2AMTA forms 2,6-diaminopurine, a fluorescent and easily quantitated product. We kinetically characterize 2AMTA with human MTAP, bacterial MTANs and use 2,6-diaminopurine as a fluorescent substrate for yeast adenine phosphoribosyltransferase. 2AMTA was used as the substrate to kinetically characterize the dissociation constants for three-transition-state analogue inhibitors of MTAP and MTAN. Kinetic values obtained from continuous fluorescent assays with MTA were in good agreement with previously measured literature values, but gave smaller experimental errors. Chemical synthesis from ribose and 2,6-dichloropurine provided crystalline 2AMTA as the oxalate salt. Chemo-enzymatic synthesis from ribose and 2,6-diaminopurine produced 2-amino-S-adenosylmethionine for hydrolytic conversion to 2AMTA. Interaction of 2AMTA with human MTAP was also characterized by pre-steady-state kinetics and by analysis of the crystal structure in a complex with sulfate as a catalytically inert analogue of phosphate. This assay is suitable for inhibitor screening by detection of fluorescent product, for quantitative analysis of hits by rapid and accurate measurement of inhibition constants in continuous assays, and pre-steady-state kinetic analysis of the target enzymes.
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PMID:Continuous Fluorescence Assays for Reactions Involving Adenine. 2777 59