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Biochemistry · Metalloenzymes: carbonic anhydrase
Sample itemA trekker taking acetazolamide for altitude sickness develops tingling and a normal anion gap metabolic acidosis. Which zinc enzyme reaction is inhibited?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. Reversible hydration of CO2 to carbonic acid, so renal bicarbonate reabsorption falls
Carbonic anhydrase is a zinc metalloenzyme that interconverts CO2 and H2O with H2CO3, which dissociates to H+ and bicarbonate. In the proximal tubule it enables bicarbonate reabsorption, so inhibition causes bicarbonaturia and hyperchloraemic (normal anion gap) acidosis. The metabolic acidosis stimulates ventilation, which is why it helps at altitude.
Option by option
A. Reversible hydration of CO2 to carbonic acid, so renal bicarbonate reabsorption falls (correct)
Correct. Inhibiting carbonic anhydrase causes bicarbonate loss and non-anion gap acidosis.
B. Decarboxylation of oxaloacetate to pyruvate, so renal bicarbonate is retained
Oxaloacetate decarboxylation does not involve zinc and is not the target of acetazolamide.
C. Oxidation of lactate to pyruvate, so lactic acid accumulates
Lactate dehydrogenase is not inhibited by acetazolamide, and lactic acidosis gives a high anion gap.
D. Conversion of angiotensin I to angiotensin II, so renal bicarbonate falls
Angiotensin converting enzyme is also a zinc enzyme, but acetazolamide does not inhibit it.
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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