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 deoxythymidylate formation and subsequent blockage of cell division is due to which of the following?
a. Since rapidly multiplying cancer cells are dependent on the synthesis of deoxythymidylate (dTMP) from deoxyuridine late (dUMP), a prime target in cancer therapy has been inhibition of dTMP synthesis.
b. The anticancer drug fluorouracil is converted in vivo to fluorodeoxy uridylate (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 participates in the change of a substrate into a covalently linked inhibitor that irreversibly inhibits its catalytic activity