In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients

M. S. Hershfield, N. M. Kredich, D. R. Ownby, H. Ownby, R. Buckley

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

The cytotoxic nucleoside 2'-deoxyadenosine is excreted in excessive amounts by individuals with genetic deficiency of adenosine deaminase, and may be in part responsible for the severe combined immune dysfunction from which they suffer. Earlier studies from this laboratory showed that 2'-deoxyadenosine causes the irreversible inactivation of the enzyme S-adenosylhomocysteine hydrolase by an active site-directed, 'suicide-like' process. In this communication the authors have demonstrated similar inactivation of S-adenosylhomocysteine hydrolase in hemolysate and in intact erythrocytes, as well as a striking deficiency of S-adenosylhomocysteine hydrolase activity in the erythrocytes of 3 adenosine deaminase-deficient patients. In vivo suicide-like inactivation of S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine may contribute to the cytotoxicity of 2'-deoxyadenosine and to the immune dysfunction in adenosine deaminase deficiency.

Original languageEnglish (US)
Pages (from-to)807-811
Number of pages5
JournalUnknown Journal
Volume63
Issue number4
DOIs
StatePublished - Jan 1 1979
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this