A 45-year-old alcoholic woman has AST 280 U/L and ALT 130 U/L. The De Ritis ratio (AST:ALT) is approximately 2.2. Which explanation best accounts for this pattern in alcoholic liver disease?

• A Alcohol upregulates ALT synthesis more than AST
• B Mitochondrial AST release and pyridoxal-5-phosphate depletion reducing ALT activity ✓
• C AST is exclusively a cytosolic enzyme more susceptible to necrosis
• D Alcohol preferentially induces ALP synthesis in hepatocytes

Explanation

In alcoholic liver disease, an AST:ALT ratio >2 (De Ritis ratio) occurs because: (1) alcohol causes mitochondrial injury releasing mitochondrial AST isoform into serum, elevating total AST disproportionately; (2) chronic alcohol intake depletes pyridoxal-5-phosphate (PLP, vitamin B6), which is a required cofactor for ALT (a purely cytosolic enzyme), reducing measured ALT activity. AST has both cytosolic and mitochondrial isoforms, so option C is wrong. ALP elevation (option D) is not the mechanism.

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

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