A 40-year-old alcoholic has a serum AST:ALT ratio of 3:1 with elevated GGT. The MOST likely biochemical reason for the disproportionate AST elevation in alcoholic liver disease is:

• A Alcohol selectively induces AST synthesis in hepatocytes
• B Alcohol directly inhibits ALT gene transcription
• C Mitochondrial dysfunction impairs pyridoxal-5-phosphate synthesis, affecting ALT more than AST ✓
• D AST is released from skeletal muscle by alcohol-induced myopathy

Explanation

Both AST and ALT require pyridoxal-5-phosphate (PLP, vitamin B6) as cofactor, but ALT is more dependent on adequate hepatic PLP stores. Alcohol depletes hepatic PLP, reducing ALT activity disproportionately compared with AST, which also has a mitochondrial isoform (mAST) released during hepatocyte injury — hence AST:ALT > 2 is characteristic of alcoholic hepatitis. GGT is induced by microsomal alcohol metabolism via CYP2E1 induction.

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

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