Figure 1: The mechanism of action of 5-FU. 5-FU is converted to three main active metabolites: fluorodeoxyuridine monophosphate (FdUMP), fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate (FUTP). FUMP is phosphorylated to fluorouridine triphosphate (FUTP), or converted to fluorodeoxyuridine diphosphate (FdUDP). In turn, FdUDP can either be phosphorylated or dephosphorylated to generate the active metabolites FdUTP and FdUMP, respectively. FdUMP acts by forming a complex with thymidylate synthase (TS), an integral component of DNA synthesis. The other active metabolite, FUTP, is integrated into cellular RNA and may alter RNA processing and function. Leucovorin (LV) increases the intracellular pool of 5,10-methylene tetrahydrofolate (CH2THF), thereby enhancing TS inhibition by FdUMP.