A patient with chronic alcoholism shows elevated AST:ALT ratio of 2.5:1 with elevated GGT. The most probable enzymatic mechanism explaining the disproportionate AST elevation is:
- A Mitochondrial AST release due to ethanol-induced mitochondrial damage ✓
- B Cytosolic AST released preferentially in alcoholic hepatitis
- C Inhibition of ALT synthesis by pyridoxal-5-phosphate deficiency
- D Enhanced hepatic uptake of plasma AST
Correct answer: A. Mitochondrial AST release due to ethanol-induced mitochondrial damage
Explanation
Chronic ethanol causes significant mitochondrial injury in hepatocytes, releasing mitochondrial AST (which constitutes 80% of total hepatic AST). This explains the AST:ALT ratio >2 characteristic of alcoholic liver disease. Additionally, ethanol-induced pyridoxal-5-phosphate (PLP) depletion reduces ALT synthesis more than AST, as ALT is more PLP-dependent. Option A is the primary mechanism. Option C is a contributing factor but not the predominant explanation. Enhanced hepatic uptake of plasma AST does not occur.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.