What does Fluorouracil inhibit to prevent tumor growth?

Fluorouracil is an antimetabolite that specifically inhibits thymidylate synthase, an enzyme crucial for DNA synthesis. Thymidylate synthase catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is a precursor for thymidine triphosphate (dTTP) necessary for DNA replication and repair. By inhibiting this enzyme, Fluorouracil effectively lowers the levels of dTTP in cells, disrupting the synthesis of DNA and ultimately hindering tumor cell proliferation.

This targeted mechanism is essential in chemotherapy, as rapidly dividing cancer cells rely heavily on the availability of nucleotides for their rapid DNA synthesis. Consequently, by blocking thymidylate synthase, Fluorouracil selectively affects tumor growth while having a more limited impact on normal cells that are not dividing as rapidly.

In contrast, while dihydrofolate reductase is inhibited by methotrexate (which impacts folate metabolism), DNA and RNA polymerases are involved in DNA replication and RNA synthesis, respectively, but are not the primary targets of Fluorouracil. Thus, its specific action on thymid