AST

**Biochemistry:** AST catalyzes: aspartate + α-ketoglutarate ⇄ oxaloacetate + glutamate. It requires pyridoxal phosphate (active form of vitamin B6) as a cofactor. Like ALT, it is a transaminase that links amino acid and TCA cycle metabolism. AST exists in cytosolic and mitochondrial isoforms; the mitochondrial form is released with more severe cell injury (contributes to the high AST:ALT ratio in alcoholic liver disease).

**Tissue distribution:** Liver, cardiac muscle, skeletal muscle, kidney, brain, and RBCs. It is less liver-specific than ALT (alanine aminotransferase), which is found mainly in the liver (cytosolic).

**Clinical significance:** - **Alcoholic hepatitis:** AST:ALT >2:1, with AST usually <300 U/L. Reasons: alcohol-induced pyridoxal phosphate (B6) deficiency (which lowers ALT more than AST), mitochondrial injury releasing mitochondrial AST. Often also elevated GGT, macrocytosis, and a history of heavy alcohol use. - **Viral hepatitis / NAFLD:** ALT ≥ AST typically (ratio <1). In acute viral hepatitis, both can reach the 1000s. In NAFLD/MASLD, ALT is generally higher than AST, but an AST:ALT ratio >1 may develop with progression to cirrhosis. - **Ischemic hepatitis ("shock liver"), acetaminophen toxicity, acute toxin injury:** Very high AST and ALT (often >1000, up to 10,000), with AST often rising earlier. - **Cirrhosis:** AST:ALT may reverse to >1 as ALT clearance falls and AST clearance by sinusoidal cells is impaired. Transaminases may be normal or only mildly elevated in end-stage disease. - **Myocardial infarction:** AST rises 6–12 h, peaks at about 24–48 h. It is no longer used for MI diagnosis (troponin is the standard). - **Skeletal muscle injury/rhabdomyolysis:** AST (and CK) is elevated. Isolated AST elevation with elevated CK suggests a muscle rather than a hepatic source. Also elevated with strenuous exercise, myopathies, and statin myopathy. - **Hemolysis:** Can mildly raise AST (RBC source), and LDH is also elevated. - **Macro-AST:** A benign cause of persistently isolated AST elevation due to AST bound to immunoglobulin.

**Pattern recognition:** - Hepatocellular pattern: AST/ALT elevated out of proportion to ALP (viral, alcohol, toxin, autoimmune, ischemic). - Cholestatic pattern: ALP and GGT elevated out of proportion to AST/ALT (biliary obstruction, PBC, PSC). - Synthetic function is assessed by albumin, PT/INR, and bilirubin, not by AST/ALT. Transaminases reflect injury, not function.

**Board pearls:** - AST:ALT >2 = alcoholic hepatitis. AST and ALT >1000 = viral hepatitis, ischemia, or acetaminophen. - Alcoholic hepatitis: "Scary" (AST) "Alcohol" (ALT lower). - Vitamin B6 deficiency (e.g., isoniazid) can impair transaminase activity and cause neuropathy. Isoniazid can also cause hepatotoxicity with a rise in AST/ALT. - Drugs that raise AST/ALT: statins, acetaminophen, isoniazid, rifampin, methotrexate, amiodarone, valproate, and many others. - Note: AST is also an abbreviation in other contexts (e.g., "antibiotic susceptibility testing" in microbiology, and "astigmatism" in ophthalmology), but on USMLE it almost always refers to aspartate aminotransferase.