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Metabolic activation of 5-fluorouracil (5-FU) to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP, TS inhibitor), 5-fluoro-2′-deoxyuridine 5′-triphosphate (FdUTP, DNA polymerase substrate), and 5-fluorouridine 5′-triphosphate (FUTP, RNA polymerase substrate). TP, thymidine phosphorylase; TK, thymidine kinase; OPRT, orotate phosphoribosyl transferase; PRPP, phosphoribosyl pyrophosphate; RNR, ribonucleotide reductase; TS, thymidylate synthase (PDB ID 1HZW).
