Fluorinated pyrimidines. XL. The reduction of 5-fluorouridine 5'-diphosphate by ribonucleotide reductase.

Abstract

A preparation of ribonucleotide reductase from Ehrlich ascites cells, free of thymidine kinase activity, catalyzes the formation of 5-fluorodeoxyuridine 59-monophosphate from enzymatically synthesize 5-fluorouridine 59-diphosphate. The product of the reaction was identified by paper chromatography before and after dephosphorylation with snake venom. The Km for 5-fluorouridine 59-diphosphate in the reactions is 0.072 mM. Experiments with several cell lines in culture reported here, as well as studies reported earlier, provide supporting evidence that, in some cells, the biosynthesis of 5-fluorodeoxyuridine 59-monophosphate from 5-fluorouracil involves the initial formation of ribonucleotides, followed by reduction to the deoxyribonucleotide by ribonucleotide reductase.