3-Deazaadenosine 5'-triphosphate: a novel metabolite of 3-deazaadenosine in mouse leukocytes.

Abstract Evidence has been obtained for the metabolic formation of small amounts (1–2% of the ATP pool) of 3-deazaadenosine 5′-triphosphate (c 3 ATP) from 3-deazaadenosine (c 3 Ado) in mouse cytolytic lymphocytes and mouse resident peritoneal macrophages. With intact leukocytes, pharmacological evidence was obtained that adenosine kinase was not the enzyme chiefly responsible for the phosphorylation of c 3 Ado. Moreover, in the presence of MgCl 2 , NaCI and IMP, purified rat liver 5′-nucleotidase catalyzed the phosphorylation of c 3 Ado to 3-deazaadenosine 5′-monophosphate (c 3 AMP). Two lines of evidence suggest that the metabolic formation of c 3 ATP is not involved in the inhibition of leukocyte function caused by c 3 Ado. First, the inhibitory action of c 3 Ado on antibody-dependent phagocytosis and lymphocyte-mediated cytolysis was reversed markedly upon removal of the drug from the medium. However, the intracellular content of c 3 ATP remained constant in lymphocytes and macrophages after removal of c 3 Ado. Second, in macrophages and in lymphocytes, similar intracellular amounts of c 3 ATP were formed from both c 3 Ado and 3-deazaadenine under conditions in which the former was biologically active and the latter was essentially inactive. Thus, it appears unlikely that the novel c 3 ATP metabolite is of relevance for the mechanism of action of c 3 Ado in mouse leukocytes.