In alcoholic liver disease, the key mechanism by which ethanol metabolism leads to hepatic steatosis involves:

• A Acetaldehyde directly inhibiting mitochondrial electron transport chain complex I
• B Increased NADH/NAD+ ratio shifting pyruvate to lactate and oxaloacetate to malate, inhibiting fatty acid oxidation and gluconeogenesis ✓
• C Ethanol-induced suppression of VLDL apoprotein synthesis causing impaired triglyceride export
• D Reactive oxygen species from CYP2E1 directly esterifying fatty acids to triglycerides

Explanation

Hepatic metabolism of ethanol by alcohol dehydrogenase generates excess NADH, dramatically raising the NADH/NAD+ ratio. This: (1) inhibits fatty acid beta-oxidation (requires NAD+), (2) diverts pyruvate to lactate and oxaloacetate to malate, blocking gluconeogenesis, and (3) promotes fatty acid synthesis, collectively leading to hepatic steatosis. While CYP2E1 generates ROS and acetaldehyde impairs mitochondria, the primary steatosis driver is the altered redox state.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.