title: Substrate inhibition of adenosine phosphorylation in adenosine deaminase deficiency and adenosine-mediated inhibition of PP-ribose-P dependent nucleotide synthesis in hypoxanthine phosphoribosyltransferase deficient erythrocytes.
abstract: The metabolism of adenosine and its effects on phosphoribosylpyrophosphate, PP-ribose-P, dependent nucleotide synthesis were studied using erythrocytes from patients with adenosine deaminase and hypoxanthine phosphoribosyltransferase deficiency as models. The phosphorylation of adenosine was progressively inhibited by concentrations of adenosine greater than 1 mumol L-1 for control and ADA deficient erythrocytes. There was essentially no initial rate of phosphorylation at 30 mumol L-1 adenosine. Adenosine, 1 mumol L-1, also caused a 60% reduction in PP-ribose-P concentration in ADA deficient erythrocytes. For HPRT deficient erythrocytes in which ADA activity was blocked by coformycin, 10 mumol L-1 inosine stimulated PP-ribose-P dependent nucleotide synthesis from adenine, whereas, 10 mumol L-1 adenosine inhibited nucleotide synthesis. These observations suggest that adenosine phosphorylation and PP-ribose-P dependent nucleotide synthesis are inhibited under conditions in which adenosine accumulates, such as in hereditary or pharmacologically induced ADA deficiency.
authors: Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
authors: F F
authors: FF
authors: Snyder
authors: C
authors: C
authors: Dyer
authors: J E
authors: JE
authors: Seegmiller
authors: R M
authors: RM
authors: Goldblum
authors: G C
authors: GC
authors: Mills
authors: F C
authors: FC
authors: Schmalstieg
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000172:deficiency*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D008297:Male; D009700:Nucleoside Deaminases / Q000172:deficiency*; D009711:Nucleotides / Q000096:biosynthesis*; D010428:Pentosephosphates / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D009711:Nucleotides; D010428:Pentosephosphates; D010754:Phosphoribosyl Pyrophosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine