Aminotransferases (Transaminases)

Biochemistry

• ALT catalyzes transfer of the amino group from alanine to alpha-ketoglutarate, forming pyruvate and glutamate.
• AST transfers the amino group from glutamate to oxaloacetate, forming alpha-ketoglutarate and aspartate (aspartate then feeds nitrogen into the urea cycle).
• Both reactions are reversible with an equilibrium constant near 1, so they function in both amino acid catabolism and biosynthesis of nonessential amino acids.
• Mechanistically, the enzyme transfers the amino group to pyridoxal phosphate (forming pyridoxamine phosphate), which then donates it to the keto-acid substrate, regenerating the coenzyme (Harper's Illustrated Biochemistry; Lippincott Biochemistry, p. 701-703).

Tissue distribution and specificity

• ALT is found predominantly in the liver (cytoplasmic enzyme), making it a fairly specific marker of hepatocellular injury.
• AST exists as both cytoplasmic and mitochondrial isoenzymes and is present in liver, cardiac muscle, skeletal muscle, kidney, brain, pancreas, lungs, leukocytes, and erythrocytes (in decreasing concentration). It is more sensitive but less liver-specific than ALT (Harrison's Principles of Internal Medicine, 22e).

Clinical significance

• Aminotransferases are the most sensitive markers of hepatocellular injury/necrosis and are most useful for detecting acute hepatocellular disease (e.g., viral hepatitis, toxic/drug-induced injury, ischemic hepatitis).
• Liver cell necrosis is not required for release; increased membrane permeability alone can cause leakage into blood.
• Pattern interpretation:
  • In most acute hepatocellular disorders, ALT ≥ AST.
  • AST:ALT ratio ≥ 2:1 suggests alcoholic liver disease (though it can also occur in cirrhosis from other causes or hepatitis C-related cirrhosis).
  • AST:ALT ratio is typically <1 in chronic viral hepatitis but tends to rise (>1) as fibrosis/cirrhosis progresses.
  • Very high levels (often >1000 IU/L) point toward acute viral hepatitis, ischemic/hypoxic hepatitis, toxin/drug-induced injury (e.g., acetaminophen), or acute biliary obstruction - a recent systematic review of transaminases >1000 IU/L found these etiologies most common (Mohamed et al., 2023, PMID 37184617).
  • Mild-to-moderate elevations are typical of NAFLD/NASH, chronic viral hepatitis, and many drug effects.
• Because AST is present in cardiac and skeletal muscle, elevated AST alone (with normal ALT) raises consideration of myocardial injury, muscle disease, or hemolysis rather than liver disease specifically.

Uses in specific contexts

• AST-to-platelet ratio index (APRI) is used as a noninvasive marker of hepatic fibrosis, including in pediatric biliary atresia (recent meta-analysis, PMID 39923745).
• In NAFLD, serum aminotransferases (ALT/AST) are commonly used to track disease activity; a 2023 meta-analysis found vitamin E supplementation modestly reduces serum aminotransferases in NAFLD patients (PMID 37686767).

Evaluation approach

• Harrison's Principles of Internal Medicine, 22e - "Evaluation of Liver Function"
• Lippincott Illustrated Reviews: Biochemistry, 8th ed. - Nitrogen Removal from Amino Acids, p. 701-703
• Tietz Textbook of Laboratory Medicine, 7th ed. - Aminotransferases
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease - Aminotransferases

• Mohamed MF et al. "Etiologies and Outcomes of Transaminase Elevation >1000 IU/L: A Systematic Review and Meta-Analysis" (PMID 37184617, 2023)
• Vogli S et al. "The Effect of Vitamin E Supplementation on Serum Aminotransferases in NAFLD: A Systematic Review and Meta-Analysis" (PMID 37686767, 2023)
• Brits E et al. "Aspartate Aminotransferase-to-platelet Ratio Index (APRi) as Biomarker for Liver Damage in Biliary Atresia" (PMID 39923745, 2025)