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Biochemistry · Folate antagonists: co-trimoxazole
Sample itemA patient with a urinary tract infection is given co-trimoxazole. Which pair of bacterial enzymes is blocked sequentially in the folate pathway?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Dihydropteroate synthase by sulfamethoxazole and dihydrofolate reductase by trimethoprim
Sulfamethoxazole is a structural analogue of para-aminobenzoic acid and inhibits dihydropteroate synthase, while trimethoprim inhibits bacterial dihydrofolate reductase with much higher affinity than the human enzyme. Sequential blockade gives synergy and bactericidal activity. Humans take folate from the diet and lack dihydropteroate synthase.
Option by option
A. Dihydropteroate synthase by trimethoprim and DNA gyrase by sulfamethoxazole
DNA gyrase is the target of fluoroquinolones, and trimethoprim acts on DHFR.
B. Dihydrofolate reductase by sulfamethoxazole and thymidylate synthase by trimethoprim
The sites are misassigned; sulfonamides act on dihydropteroate synthase, not DHFR.
C. Dihydropteroate synthase by sulfamethoxazole and dihydrofolate reductase by trimethoprim (correct)
Correct. Two consecutive steps are blocked, one by each drug.
D. Thymidylate synthase by sulfamethoxazole and dihydropteroate synthase by trimethoprim
Sulfonamides do not inhibit thymidylate synthase, and trimethoprim does not act on dihydropteroate synthase.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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