Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are used clinically to assess hepatocellular damage. Both are transaminases requiring PLP. In alcoholic liver disease, the AST/ALT ratio typically exceeds 2:1. This is primarily because:

• A Alcohol directly inhibits ALT gene transcription in hepatocytes
• B AST activity increases because alcohol induces AST gene expression via nuclear factor kappa-B
• C ALT is predominantly found in muscle, not liver, so hepatic injury does not increase ALT significantly
• D Mitochondrial AST is released from alcohol-damaged mitochondria, and chronic alcohol consumption depletes vitamin B6, disproportionately reducing ALT (which has lower baseline activity) more than AST ✓

Explanation

The AST:ALT > 2 ratio in alcoholic liver disease reflects several factors: alcohol preferentially damages mitochondria, releasing the mitochondrial isoform of AST (m-AST, which constitutes ~80% of hepatic AST); chronic alcoholism depletes pyridoxal phosphate (PLP), and ALT is more dependent on adequate PLP concentrations than AST (AST has higher affinity for PLP), so ALT activity is disproportionately reduced; and acetaldehyde specifically inhibits ALT. The absolute values in alcoholic hepatitis rarely exceed 300-400 U/L, distinguishing it from acute viral hepatitis where values are commonly >1000 U/L.

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

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Written and medically reviewed by the StethoPrep medical team.