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Pharmacology · Chemotherapy: capecitabine activation
Sample itemCapecitabine is an oral prodrug converted to fluorouracil in three steps, and the final step occurs preferentially in tumour tissue. Which enzyme catalyses this final step?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. Thymidine phosphorylase
Capecitabine is first hydrolysed by carboxylesterase in the liver, then converted by cytidine deaminase to 5-deoxy-5-fluorouridine, and finally to fluorouracil by thymidine phosphorylase. Tumours often have higher thymidine phosphorylase levels than normal tissue, which gives some selectivity.
Option by option
A. Dihydropyrimidine dehydrogenase
Dihydropyrimidine dehydrogenase degrades fluorouracil and does not activate it.
B. Cytidine deaminase
Cytidine deaminase catalyses the second step, forming deoxyfluorouridine.
C. Carboxylesterase
Carboxylesterase catalyses the first step in the liver.
D. Thymidine phosphorylase (correct)
Correct. Thymidine phosphorylase forms fluorouracil in the last step and is raised in many tumours.
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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