aminotransferase
Summary
Aminotransferases (transaminases) are enzymes that catalyze the transfer of an amino group between an amino acid and an α-keto acid, playing a key role in amino acid metabolism and gluconeogenesis. ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are the two clinically important isoforms used as serum markers of hepatocellular injury. ALT is more liver-specific, while AST is also found in cardiac and skeletal muscle, kidney, and brain.
Detail
Aminotransferases require pyridoxal phosphate (vitamin B6) as a cofactor and catalyze reversible transamination reactions, transferring an amino group from an amino acid to α-ketoglutarate, forming glutamate and a new α-keto acid. ALT catalyzes conversion of alanine + α-ketoglutarate ↔ pyruvate + glutamate, while AST catalyzes aspartate + α-ketoglutarate ↔ oxaloacetate + glutamate. These reactions are central to amino acid catabolism, funneling nitrogen into the urea cycle and carbon skeletons into the TCA cycle/gluconeogenesis (alanine-glucose cycle).
Clinically, serum ALT and AST are used as biomarkers of hepatocyte injury. ALT is more specific to the liver (cytosolic enzyme), whereas AST is present in liver, cardiac muscle, skeletal muscle, kidneys, brain, and RBCs, and exists in both cytosolic and mitochondrial forms.
Patterns of elevation are diagnostically useful: - AST:ALT ratio >2:1 suggests alcoholic liver disease (due to mitochondrial injury and B6 deficiency reducing ALT synthesis). - ALT > AST is typical of viral hepatitis and NAFLD/NASH. - Markedly elevated transaminases (>1000s) suggest acute viral hepatitis, ischemic hepatitis (shock liver), or drug-induced liver injury (e.g., acetaminophen toxicity). - Mild-moderate elevations (<300-500) are seen in chronic hepatitis, fatty liver, and cholestatic disease. - AST elevation without liver disease can occur in MI, rhabdomyolysis, or hemolysis, but cardiac biomarkers (troponin, CK-MB) have replaced AST for MI diagnosis.
Aminotransferases are part of the standard liver function panel alongside alkaline phosphatase, bilirubin, and albumin, and are essential for differentiating hepatocellular vs cholestatic injury patterns.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- Lippincott Biochemistry
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