aspartate aminotransferase

**Biochemistry** - Reaction: Aspartate + alpha-ketoglutarate <-> oxaloacetate + glutamate (reversible transamination). - Cofactor: pyridoxal phosphate (active form of vitamin B6). Deficiency (e.g., isoniazid therapy) can lower aminotransferase activity. - Isoforms: cytosolic and mitochondrial. Mitochondrial AST is released with severe cell injury, and a high mitochondrial AST fraction is seen in alcoholic hepatitis. - Role: links amino acid and carbohydrate metabolism. It feeds the urea cycle (aspartate supplies the second nitrogen for argininosuccinate) and the malate-aspartate shuttle.

**Tissue distribution** - Liver, cardiac muscle, skeletal muscle, kidney, brain, and RBCs. - Because it is not liver-specific, AST is less specific for hepatocellular injury than ALT (alanine aminotransferase), which is mainly in the liver (cytosolic).

**Clinical significance** - **Alcoholic liver disease:** AST:ALT >2:1, with AST usually <300 U/L. Contributing factors are alcohol-induced mitochondrial injury (AST is also mitochondrial) and pyridoxal phosphate depletion, which lowers ALT more than AST. - **Viral hepatitis, NAFLD/NASH:** ALT is usually higher than AST (ratio <1). In viral hepatitis, ALT/AST can reach the thousands in the acute phase. - **Ischemic hepatitis ("shock liver"), acetaminophen toxicity:** Marked elevations (often >1000 U/L), sometimes with AST rising earlier. - **Cirrhosis:** The ratio may reverse to AST >ALT (>1) as disease advances. - **Myocardial infarction:** AST rises 6-12 hours after MI, peaks at about 24 hours, and returns to normal in 4-7 days. It is no longer used for MI diagnosis, because troponin has replaced it. - **Skeletal muscle injury (rhabdomyolysis, myopathy, strenuous exercise):** AST rises along with CK. This is an important cause of isolated AST elevation. - **Hemolysis:** Falsely elevated in vitro or true elevation from RBC release. - **Macro-AST:** AST bound to immunoglobulin gives a persistently isolated AST elevation, with no disease.

**Interpretation pearls** - Hepatocellular pattern: AST and ALT elevated out of proportion to ALP. Cholestatic pattern: ALP and GGT elevated out of proportion. - AST and ALT reflect hepatocyte injury, not hepatic synthetic function. For synthetic function, use albumin, PT/INR, and bilirubin. - Isolated AST elevation with normal ALT should prompt a search for a non-hepatic source (muscle, heart, hemolysis). - The AST:ALT ratio is also a component of fibrosis scores (e.g., FIB-4, APRI).

**Mnemonic:** "Two drinks (2:1) = AST > ALT." "AST is Alcohol, ALT is viruses/fat (NAFLD)."