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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
Author(s) -
Snyder F. F.,
Dyer C.,
Seegmiller J. E.,
Goldblum R. M.,
Mills G. C.,
Schmalstieg F. C.
Publication year - 1988
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799869
Subject(s) - adenosine deaminase , adenosine , hypoxanthine phosphoribosyltransferase , adenosine deaminase deficiency , adenine phosphoribosyltransferase , nucleotide , ribose , hypoxanthine , biochemistry , chemistry , deoxyadenosine , amp deaminase , purine , hypoxanthine guanine phosphoribosyltransferase , biology , microbiology and biotechnology , enzyme , gene , mutant
Summary 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 µmol L −1 for control and ADA deficient erythrocytes. There was essentially no initial rate of phosphorylation at 30 µmol L −1 adenosine. Adenosine, 1 µmol 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 µmol L −1 inosine stimulated PP‐ribose‐P dependent nucleotide synthesis from adenine, whereas, 10 µmol 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.