Which enzyme do Trimethoprim/Pyrimethamine drugs target?

• A. Dihydrofolate reductase (DHF --> THF)
• B. Dihydropteroate synthase (PABA --> DHF)
• C. Dihydrofolate synthase
• D. Thymidylate synthase

Answer: (A)

Antifolate drugs like Trimethoprim and pyrimethamine work by blocking dihydrofolate reductase, the enzyme that converts dihydrofolate into tetrahydrofolate. Without tetrahydrofolate, the cell cannot carry out essential one-carbon transfer reactions needed to synthesize purines and thymidylate, so DNA synthesis is impaired and cell growth stops. This makes the drug effective against bacteria (Trimethoprim) and parasites (pyrimethamine).

Dihydropteroate synthase is targeted by sulfonamides, not these drugs; thymidylate synthase uses the tetrahydrofolate pool to make thymidylate but is not the enzyme inhibited here; and there isn’t a standard dihydrofolate synthase step in this pathway.