Ethanol oxidizes to acetaldehyde via alcohol dehydrogenase (ADH; cytosolic, gastric + hepatic) and then to acetate via aldehyde dehydrogenase (ALDH2; mitochondrial). Acetaldehyde is the toxic intermediate responsible for hangover symptoms + carcinogenicity. ALDH2*2 polymorphism (Glu487Lys) is common in East Asian populations (~30-50%) and produces dramatically reduced ALDH2 activity — the basis for "Asian flush" with even small ethanol doses. DISULFIRAM inhibits ALDH2 pharmacologically, producing the same accumulation of acetaldehyde — used as aversion therapy for alcohol-use disorder. Metronidazole + cefoperazone + certain other antibiotics produce a similar disulfiram-like reaction.
Organ Systems
digestive
nervous
Pathway Steps
ethanol → acetaldehyde — via alcohol dehydrogenase (ADH; cytosolic; multiple isoforms ADH1-5). Alcohol dehydrogenase (cytosolic) oxidizes ethanol to toxic acetaldehyde, consuming NAD⁺; the high NADH/NAD⁺ ratio drives lactate (acidosis), suppresses gluconeogenesis (fasting hypoglycemia), and promotes fatty liver. CYP2E1 contributes more with chronic intake.
acetaldehyde → acetate — via aldehyde dehydrogenase 2 (ALDH2; mitochondrial) — DISULFIRAM TARGET. Mitochondrial ALDH2 detoxifies acetaldehyde; the common East-Asian ALDH2*2 loss-of-function variant lets acetaldehyde accumulate (alcohol-flush reaction, higher esophageal-cancer risk). Disulfiram inhibits ALDH2 deliberately to deter drinking.
Known Modulators
ethanol (substrate) — ADH step. Also undergoes MM elimination (authored at v1.0): Vmax 230 mg/L/h, Km 80 mg/L (Holford 1987 PMID:3319346).