alcohol dehydrogenase
Summary
Alcohol dehydrogenase (ADH) is the primary enzyme responsible for ethanol metabolism, converting ethanol to acetaldehyde in the liver. It follows zero-order kinetics at high alcohol concentrations and is the rate-limiting step in alcohol elimination. ADH polymorphisms affect alcohol tolerance and susceptibility to alcoholism.
Detail
Alcohol dehydrogenase is a zinc-containing enzyme primarily located in liver hepatocytes that catalyzes the first step of ethanol metabolism: ethanol + NAD+ → acetaldehyde + NADH + H+. The enzyme exhibits zero-order kinetics at blood alcohol levels >20 mg/dL, meaning it metabolizes alcohol at a constant rate (~1 drink/hour) regardless of concentration. ADH has multiple isoforms with different kinetic properties - Class I ADH (stomach and liver) has high affinity but low capacity, while Class II has lower affinity but higher capacity. Genetic polymorphisms significantly affect enzyme activity: ADH1B*2 (common in East Asians) metabolizes ethanol rapidly, while ALDH2 deficiency causes acetaldehyde accumulation, leading to flushing syndrome and reduced alcohol tolerance. The NADH produced during ADH activity affects hepatic metabolism, inhibiting gluconeogenesis (causing hypoglycemia) and fatty acid oxidation (promoting fatty liver). ADH also metabolizes methanol and ethylene glycol, making ethanol a competitive inhibitor used therapeutically in poisoning cases.
Sources
- Lippincott Illustrated Reviews: Biochemistry
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- Robbins Basic Pathology
- First Aid for the USMLE Step 1
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.