A chronic alcoholic who has been drinking heavily without eating for two days is found drowsy with blood glucose of 40 mg/dL. Which mechanism best accounts for the hypoglycemia?
- A Ethanol stimulates insulin secretion and suppresses glucagon
- B Acetaldehyde directly inhibits glycogen phosphorylase in the liver
- C High NADH from ethanol metabolism diverts oxaloacetate to malate, limiting gluconeogenesis ✓
- D Ethanol competitively blocks hepatic glucose transporters
Correct answer: C. High NADH from ethanol metabolism diverts oxaloacetate to malate, limiting gluconeogenesis
Explanation
Alcohol dehydrogenase converts ethanol to acetaldehyde using NAD+, producing excess cytosolic NADH. This drives oxaloacetate reduction to malate, depleting the substrate for phosphoenolpyruvate carboxykinase and impairing gluconeogenesis, especially when glycogen stores are already exhausted by fasting. Ethanol does not stimulate insulin secretion, and it does not block GLUT transporters or inhibit phosphorylase, which eliminates the other three mechanisms.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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