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Biochemistry · Amino acid metabolism: isoniazid seizures and GABA synthesis
Sample itemA patient who swallowed a large quantity of isoniazid presents with refractory seizures. Which metabolic defect explains the fits, and what corrects it?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. Impaired GABA synthesis by glutamate decarboxylase, corrected by pyridoxine
Isoniazid forms a hydrazone with pyridoxal and inhibits pyridoxal kinase, causing functional pyridoxal phosphate deficiency. Glutamate decarboxylase needs pyridoxal phosphate, so GABA falls and seizures follow. Intravenous pyridoxine is the antidote.
Option by option
A. Impaired acetylcholine synthesis by choline acetyltransferase, corrected by thiamine
Choline acetyltransferase does not require thiamine, and acetylcholine deficiency is not the cause of these fits.
B. Impaired noradrenaline synthesis by dopamine beta-hydroxylase, corrected by ascorbate
Dopamine beta-hydroxylase needs copper and ascorbate, and its failure does not explain isoniazid seizures.
C. Impaired glutamate formation by glutamate dehydrogenase, corrected by riboflavin
Glutamate dehydrogenase uses NAD(P) and its loss would not cause seizure through this route; riboflavin is not the antidote.
D. Impaired GABA synthesis by glutamate decarboxylase, corrected by pyridoxine (correct)
Correct. PLP is the cofactor of glutamate decarboxylase, and pyridoxine restores 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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