## Methanol Metabolism **Key Point:** Methanol undergoes two-step oxidation via alcohol dehydrogenase (ADH), the same enzyme that metabolizes ethanol. ### Sequential Oxidation 1. **First step:** Methanol → Formaldehyde (via ADH) 2. **Second step:** Formaldehyde → Formic acid (via aldehyde dehydrogenase) **High-Yield:** Formic acid is the toxic metabolite responsible for methanol poisoning — it causes metabolic acidosis, optic nerve damage, and CNS toxicity. ### Clinical Relevance **Clinical Pearl:** Ethanol is used as an antidote in methanol poisoning because it competitively inhibits ADH, preventing the conversion of methanol to its toxic metabolites. This buys time for dialysis. ### Why ADH is the Answer ADH has high affinity for both ethanol and methanol; it catalyzes the rate-limiting first oxidation step. Aldehyde dehydrogenase (not aldehyde oxidase) catalyzes the second step. **Mnemonic:** **ADH-ADH pathway** — Alcohol DeHydrogenase converts methanol to formaldehyde; Aldehyde DeHydrogenase converts formaldehyde to formic acid.
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