Which enzyme is inhibited by sulfonamides in the folate synthesis pathway?

• A. Dihydrofolate reductase
• B. RNA polymerase
• C. Dihydropteroate synthase
• D. DNA polymerase

Answer: (C)

Sulfonamides block a step early in bacterial folate synthesis by acting as false substrates that resemble PABA. They fit into the active site of dihydropteroate synthase, preventing the enzyme from combining PABA with the other building block to form dihydropteroate. Without dihydropteroate, the folate pathway stalls, and the bacterium can’t produce tetrahydrofolate derivatives needed for thymidine and purine synthesis, crippling DNA replication and cell growth. Humans don’t make folate and obtain it from our diet, so this pathway is present in bacteria but not in the same form in our cells, which is why sulfonamides selectively disrupt bacterial growth.

Other enzymes listed aren’t targeted by sulfonamides. For example, dihydrofolate reductase is inhibited by a different drug, and RNA or DNA polymerases are affected by other classes of antibiotics.