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Biochemistry · Amino acid metabolism: pyridoxal phosphate
Sample itemA 40-year-old malnourished man on a regimen containing isoniazid develops numbness and tingling of both feet. Which biochemical change underlies this neuropathy?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Depletion of pyridoxal phosphate, the cofactor for transaminases and decarboxylases
Isoniazid reacts with pyridoxal phosphate to form an inactive hydrazone and increases pyridoxine excretion, so the active coenzyme falls. Pyridoxal phosphate is required for transamination, decarboxylation (for GABA, serotonin, dopamine and histamine) and heme synthesis, and its deficiency produces peripheral neuropathy. Malnourished patients and alcoholics are at special risk.
Option by option
A. Depletion of NAD+ because tryptophan is not absorbed
NAD+ deficiency from poor tryptophan absorption describes Hartnup disease or pellagra, not isoniazid toxicity.
B. Depletion of adenosylcobalamin, the cofactor for methylmalonyl-CoA mutase
Cobalamin deficiency is not produced by isoniazid.
C. Depletion of pyridoxal phosphate, the cofactor for transaminases and decarboxylases (correct)
Correct. Isoniazid inactivates pyridoxal phosphate and impairs amino acid transformations in nerves.
D. Depletion of thiamine pyrophosphate, the cofactor for pyruvate dehydrogenase
Thiamine deficiency causes beriberi, a different clinical syndrome, and isoniazid does not inactivate 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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