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

F. F. Snyder, C. Dyer, J. E. Seegmiller, R. M. Goldblum, G. C. Mills, F. C. Schmalstieg

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalJournal of Inherited Metabolic Disease
Volume11
Issue number2
DOIs
StatePublished - Jun 1988

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Hypoxanthine Phosphoribosyltransferase
Ribose
Adenosine
Nucleotides
Erythrocytes
Phosphorylation
Coformycin
Lesch-Nyhan Syndrome
Inosine
Adenosine Deaminase
Adenine Nucleotides
Severe combined immunodeficiency due to adenosine deaminase deficiency

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

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. / Snyder, F. F.; Dyer, C.; Seegmiller, J. E.; Goldblum, R. M.; Mills, G. C.; Schmalstieg, F. C.

In: Journal of Inherited Metabolic Disease, Vol. 11, No. 2, 06.1988, p. 174-183.

Research output: Contribution to journalArticle

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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 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.",
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AU - Seegmiller, J. E.

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AB - 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.

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