A 45-year-old woman with alcoholic liver disease has AST:ALT ratio of 2.8:1. This ratio is elevated because:

• A Alcohol induces hepatic ALT synthesis selectively
• B Alcohol depletes pyridoxal phosphate, reducing ALT activity more than AST ✓
• C Mitochondrial AST released by alcohol-induced mitochondrial damage exceeds cytosolic ALT
• D ALT is excreted into bile while AST remains in plasma

Explanation

Both AST and ALT require pyridoxal phosphate (vitamin B6) as a cofactor. Chronic alcohol use causes depletion of pyridoxal phosphate; however, hepatic ALT has a much higher affinity for pyridoxal phosphate and its activity falls proportionately more with B6 deficiency, depressing plasma ALT release. Additionally, alcohol-induced mitochondrial damage releases the mitochondrial isoform of AST. Together, these mechanisms elevate the AST:ALT ratio above 2:1 in alcoholic hepatitis, distinguishing it from non-alcoholic or viral hepatitis where the ratio is typically <1.

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

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