Which of the following enzymes is responsible for the metabolism of methanol to its toxic metabolite formaldehyde?

Explanation

## Methanol Metabolism Pathway **Key Point:** Methanol is metabolized in two sequential steps, both catalyzed by alcohol dehydrogenase (ADH): 1. Methanol → Formaldehyde (via ADH) 2. Formaldehyde → Formic acid (via aldehyde dehydrogenase) ### Why ADH is the Critical Enzyme Alcohol dehydrogenase is the first and rate-limiting enzyme in methanol detoxification. This is clinically important because: - Ethanol competes with methanol for ADH binding - Ethanol has higher affinity for ADH than methanol - This competition is the basis for ethanol therapy in methanol poisoning ### Metabolic Pathway ```mermaid flowchart LR A[Methanol] -->|ADH| B[Formaldehyde] B -->|Aldehyde dehydrogenase| C[Formic acid] C -->|Accumulates| D[Metabolic acidosis<br/>Optic nerve damage]:::urgent E[Ethanol] -->|Competes for ADH| F[Blocks methanol<br/>metabolism]:::action ``` **High-Yield:** The toxic metabolites are formic acid and formaldehyde, not methanol itself. Formic acid causes the characteristic metabolic acidosis and optic nerve toxicity (blindness) seen in methanol poisoning. **Clinical Pearl:** In methanol poisoning, ethanol is given as an antidote because it preferentially binds ADH, preventing the conversion of methanol to its toxic metabolites. This allows methanol to be excreted unchanged in urine. **Mnemonic:** **MAD** = **M**ethanol → **A**lcohol dehydrogenase → **D**angerous metabolites