## Methanol Metabolism Pathway **Key Point:** Methanol undergoes a two-step oxidation process via alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ### Step-by-Step Conversion 1. **Methanol → Formaldehyde**: Catalyzed by **alcohol dehydrogenase (ADH)** 2. **Formaldehyde → Formic acid**: Catalyzed by **aldehyde dehydrogenase (ALDH)** 3. **Formic acid accumulation**: Causes metabolic acidosis and ocular toxicity ### Why This Matters in Poisoning **High-Yield:** The primary toxin is **formic acid**, not methanol itself. Formic acid causes: - Severe metabolic acidosis - Optic nerve damage → blindness - CNS depression **Clinical Pearl:** Ethanol competes with methanol for ADH, slowing methanol metabolism and allowing time for elimination via kidneys before toxic metabolites accumulate. This is the rationale for ethanol therapy in methanol poisoning. ### Enzyme Specificity | Enzyme | Substrate | Product | Role in Methanol Poisoning | |--------|-----------|---------|---------------------------| | **Alcohol dehydrogenase (ADH)** | Methanol | Formaldehyde | **First oxidation step** | | Aldehyde dehydrogenase (ALDH) | Formaldehyde | Formic acid | Second oxidation step | | Catalase | H₂O₂ | H₂O + O₂ | Minor pathway, not rate-limiting | | Monoamine oxidase | Biogenic amines | Aldehydes | Unrelated to alcohol metabolism | **Mnemonic:** **ADH = Alcohol Dehydrogenase** — the first enzyme in the toxic cascade for methanol.
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