Alcohol Metabolism: How the Body Breaks Down Ethanol via ADH, ALDH, and CYP450

Primary Pathway (Cytosolic)

1. Alcohol dehydrogenase (ADH): Ethanol + NAD⁺ → Acetaldehyde + NADH + H⁺. Multiple isozymes (ADH1B, ADH1C polymorphisms affect rate).
2. Aldehyde dehydrogenase (ALDH2): Acetaldehyde + NAD⁺ + H₂O → Acetate + NADH + H⁺. ALDH2*2 variant (common in East Asians) causes flushing, tachycardia, nausea.

Secondary Pathways

• Microsomal ethanol-oxidizing system (MEOS / CYP2E1): Inducible by chronic alcohol; oxidizes ethanol to acetaldehyde, generates ROS. Contributes ~10% at low BAC, up to 30% at high BAC.
• Catalase (peroxisomal): Minor role; uses H₂O₂ to oxidize ethanol.

Fate of Acetate

Acetate → acetyl-CoA → enters Krebs cycle or fatty acid synthesis. Excreted in urine, sweat, breath (minor).

Kinetics & Variability

• Zero-order elimination at typical BAC (constant rate ~7–10 g/hr or 0.015–0.020% BAC/hr).
• Factors: genetics (ADH/ALDH variants), sex (lower gastric ADH in women), age, body water, food, liver health, medications.

Clinical Relevance

• Disulfiram inhibits ALDH2 → acetaldehyde accumulation → deterrent.
• CYP2E1 induction → altered drug metabolism, oxidative stress.
• Breathalyzer measures alveolar ethanol equilibrium.