The chemotherapy drug fluorouracil undergoes a series of chemical changes in vivo that result in a covalent complex such that it is bound to both thymidylate synthase and methylene-tetrahydrofolate. The inhibition of deoxythymidilate formation and subsequent blockage of cell division is due to

Since rapidly multiplying cancer cells are dependent upon the synthesis of deoxythymidilate (dTMP) from deoxyuridylate (dUMP), a prime target in cancer therapy has been inhibition of dTMP synthesis. The anticancer drug fluorouracil is conveed in vivo to fluorodeoxyuridylate (FdUMP), which is an analogue of dUMP. FdUMP irreversibly forms a covalent complex with the enzyme thymidylate synthase and its substrate N5,N10-methylene- tetrahydrofolate. This is a case of suicide inhibition, where an enzyme actually paicipates in the change of a substrate into a covalently linked inhibitor that irreversibly inhibits its catalytic activity.