A 45-year-old alcoholic presents with serum AST 280 U/L, ALT 110 U/L, and markedly elevated GGT. The AST:ALT ratio of >2 in alcoholic liver disease is PRIMARILY due to:

• A Preferential hepatocyte necrosis in the periportal zone releasing more AST
• B Mitochondrial damage by ethanol causing selective release of mitochondrial AST isoenzyme
• C Depletion of pyridoxal phosphate (vitamin B6) by ethanol, which disproportionately impairs ALT synthesis ✓
• D Induction of AST gene transcription by acetaldehyde in hepatocytes

Explanation

ALT synthesis requires pyridoxal phosphate as a cofactor more than AST does; chronic alcohol consumption depletes vitamin B6 (pyridoxal phosphate), which disproportionately reduces ALT activity, thereby raising the AST:ALT ratio. Additionally, ethanol causes mitochondrial dysfunction that releases mitochondrial AST isoenzyme, further contributing to elevated AST. The De Ritis ratio (AST:ALT >2) is the hallmark of alcoholic hepatitis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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