Q.67. The antibacterial trimethoprim is an inhibitor of
(A) dihydrofolate reductase
(B) dihydropteroate synthetase
(C) 𝑁5, 𝑁𝐼0-methenyl tetrahydrofolate synthetase
(D) serine hydroxymethyl transferase
Trimethoprim targets bacterial folate synthesis as a key antibacterial agent. The correct answer to the MCQ is (A) dihydrofolate reductase, with detailed explanations for all options below.
Correct Answer
Trimethoprim acts as a competitive inhibitor of dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF) essential for bacterial DNA and protein synthesis. This selectivity arises from trimethoprim’s 60,000-fold higher affinity for bacterial DHFR over the human enzyme, making it effective against pathogens like E. coli while sparing host cells. Often combined with sulfamethoxazole, it synergistically halts folate production upstream and downstream.
Option Breakdown
-
(A) Dihydrofolate reductase: Correct. Trimethoprim binds DHFR, preventing THF formation and halting thymidine synthesis for bacterial DNA.
-
(B) Dihydropteroate synthetase: Incorrect. This enzyme is inhibited by sulfonamides (e.g., sulfamethoxazole), which block para-aminobenzoic acid (PABA) incorporation into dihydropteroate, the precursor to DHF.
-
(C) N5,N10-methenyl tetrahydrofolate synthetase: Incorrect. This enzyme (also called methenyltetrahydrofolate synthetase) interconverts folate forms in one-carbon metabolism; trimethoprim does not target it.
-
(D) Serine hydroxymethyl transferase: Incorrect. SHMT transfers one-carbon units from serine to THF for purine and thymidylate synthesis, unrelated to trimethoprim’s DHFR inhibition.
Folate Pathway Context
Bacteria synthesize folate de novo, unlike humans who obtain it from diet, enabling selective inhibition. Trimethoprim disrupts the final step (DHF to THF), while sulfonamides block earlier dihydropteroate formation, explaining their combination therapy like co-trimoxazole. This pathway is a prime target for antibacterials in exams on antimicrobial mechanisms.
