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Biochemistry · Enzyme inhibition: methanol poisoning
Sample itemA 30-year-old man develops blurred vision and a high anion gap metabolic acidosis after drinking adulterated country liquor containing methanol. Fomepizole is given. How does it work?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. Competitively inhibits alcohol dehydrogenase, preventing formation of formaldehyde and formic acid
Methanol is oxidised by alcohol dehydrogenase to formaldehyde and then formate, the toxin that injures the optic nerve and causes acidosis. Fomepizole binds alcohol dehydrogenase with much higher affinity than methanol, so the toxic metabolites are not formed, and ethanol acts the same way when fomepizole is unavailable. Haemodialysis removes methanol and formate in severe cases.
Option by option
A. Chelates formic acid in the circulation
Fomepizole does not chelate formate; it acts at the first enzyme step.
B. Irreversibly inactivates aldehyde dehydrogenase
Inhibiting aldehyde dehydrogenase is the action of disulfiram and would not stop toxic metabolite formation.
C. Activates the cytochrome P450 system to detoxify methanol
Fomepizole does not induce P450 enzymes and does not detoxify methanol.
D. Competitively inhibits alcohol dehydrogenase, preventing formation of formaldehyde and formic acid (correct)
Correct. A higher-affinity competitive inhibitor blocks activation of methanol.
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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