Figure 1. Metabolic pathways and mechanism of action of 5-fluorouracil (5-FU). Enzymes catalyzing these reactions are 1, orotate phosphoribosyltransferase; 2, uridine phosphorylase; 3, thymidine phosphorylase; 4, uridine kinase; 5, thymidine kinase; 6, thymidylate synthase; 7, dihydrofolate reductase; 8, dihydropyrimidine dehydrogenase; 9, ribonucleotide reductase; 10, 5'-nucleotidases and phosphatases. FUMP, FUDP, FUTP: fluorouridine -5'-mono-, di-, and triphosphate, respectively; FdUMP, FdUDP, FdUTP: fluorodeoxyuridine-5'-mono-, di-, and triphosphate, respectively; dUMP: deoxyuridine-5'-monophosphate; dTMP, dTDP, dTTP: deoxythymidine-5'-mono-, di-, and triphosphate, respectively; PRPP: 5-phosphoribosyl-1-pyrophosphate; FUR: fluorouridine; FUdR: fluorodeoxyuridine; F-BAL: a-fluoro-ß-alanine; F-UPA: fluoroureidopropionate; F-DHU: 5-fluorodihydrouracil; DHF: dihydrofolate; THF: tetrahydrofolate; TdR: thymidine; PPi: pyrophosphate. Modified from Ref. 61.