Methanol is converted to formaldehyde and formic acid by which enzyme system?

Explanation

## Methanol Metabolism **Key Point:** Methanol undergoes two-step oxidation to its toxic metabolites via alcohol dehydrogenase (ADH), the same enzyme that metabolizes ethanol. ### Metabolic Pathway 1. **First oxidation:** Methanol → Formaldehyde (via ADH) 2. **Second oxidation:** Formaldehyde → Formic acid (via aldehyde dehydrogenase) Formic acid is the primary toxic metabolite responsible for methanol poisoning, causing metabolic acidosis and optic nerve damage. ### Why ADH is the Rate-Limiting Step **High-Yield:** ADH has higher affinity for ethanol than methanol. This is why ethanol is used as an antidote in methanol poisoning — it competitively inhibits ADH, slowing methanol oxidation and allowing renal excretion of unchanged methanol. ### Clinical Significance **Clinical Pearl:** The latent period (6–30 hours) in methanol poisoning reflects the time needed for ADH to convert methanol to formic acid. Early symptoms may be absent despite high blood methanol levels. | Metabolite | Enzyme | Toxicity | |---|---|---| | Methanol | — | Minimal | | Formaldehyde | ADH | Moderate (transient) | | Formic acid | Aldehyde dehydrogenase | **Severe** (metabolic acidosis, blindness) | **Mnemonic:** **MAFF** — Methanol → Alcohol dehydrogenase → Formaldehyde → Formic acid (toxic)