THE ENZYMIC FORMATION OF 6-(METHYLMERCAPTO)PURINE RIBONUCLEOSIDE 5′-PHOSPHATE

Abstract

6-(Methylmercapto)purine ribonucleoside (Me6MPR) is efficiently phosphorylated in mouse tissues and in Ehrlich ascites carcinoma cells in vivo; tumor cells in vitro and cell-free extracts of the tumor also phosphorylate this analogue ribonucleoside. The product of this reaction has been identified by chemical and enzymatic methods and by its chromatographic behaviour as Me6MPR 5′-phosphate. The evidence presented in this report indicates that no other major metabolites of Me6MPR are formed.The phosphorylation of Me6MPR by cell-free tumor extracts requires ATP and Mn2+(or Mg2+), and evidence is presented that the reaction is probably mediated by adenosine kinase.Me-14C-6MPR is rapidly taken up by most mouse tissues following its intraperitoneal injection. Forty minutes after injection of the labeled drug, the highest levels of radioactivity were found in intestine, liver, blood cells, lung, and spleen, in descending order; virtually no radioactivity was found in brain tissue or in blood plasma.