Disulfiram (Antabuse) works by inhibiting which enzyme, leading to acetaldehyde accumulation when alcohol is consumed?
- A Alcohol dehydrogenase (ADH)
- B Aldehyde dehydrogenase (ALDH), particularly ALDH2 ✓
- C Cytochrome P450 2E1 (CYP2E1)
- D Catalase in peroxisomes
Correct answer: B. Aldehyde dehydrogenase (ALDH), particularly ALDH2
Explanation
Disulfiram inhibits aldehyde dehydrogenase (specifically mitochondrial ALDH2), the enzyme that converts acetaldehyde to acetate in the second step of ethanol metabolism. This causes acetaldehyde accumulation, producing the aversive disulfiram-alcohol reaction (flushing, nausea, palpitations, hypotension). Alcohol dehydrogenase converts ethanol to acetaldehyde in the first step and is not inhibited by disulfiram. Acamprosate, not disulfiram, modulates NMDA/GABA receptors to reduce craving.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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