Alanine aminotransferase - ALT
Glutamic pyruvic transaminase, GPT

Alanine amino transferase catalyzes the transfer of the alpha amino group of alanine to alpha- ketoglutaric acid, resulting in the formation of pyruvic and glutamic acid. ALT is located in the cytoplasm and like AST, requires P5P for maximal enzyme activity. It is useful as a specific indicator of hepatocellular injury in dogs and cats. ALT is not a useful indicator of liver disease in large animals, including pigs, due to low enzyme activity in liver tissue of these species. SDH and GLDH is a viable alternative to ALT in all species.
Serum half-life is 59 hours in dogs and < 24 hours in cats. Following acute hepatic injury, serum enzyme activity peaks at about 48 hours and then begins to decrease.
Increases in the enzyme occur due to cell damage (increased membrane permeability or necrosis) and induction (increased synthesis).

Organ specificity

ALT is virtually liver specific in dogs, cats, rabbits, rats and primates. Some increases are possible in severe muscle diseases of the dog and cat due to release of enzyme from this tissue. ALT is found in the liver, muscle (cardiac and skeletal), kidneys, and erythocytes.

Causes of increased ALT
  • Artifact: Hemolysis will cause increased levels in the cat. Cats have a high RBC to plasma ALT ratio. Hemolysis has a minimal effect on ALT in cattle, horses, and dogs.

  • Drugs: Anticonvulsants (primidone, phenobarbitone, dilantin) increase ALT 4 x normal. Although these drugs may induce ALT synthesis, increases in ALT are thought to be secondary to hepatocellular necrosis. Corticosteroids increase ALT to approximately 2-3 x normal. Levels are greater in steroid hepatopathy (where actual hepatocellular injury occurs). This is currently attributed to altered permeability and not due to increased synthesis, as previously thought. Any drugs that can cause hepatotoxicity can result in increased ALT levels, e.g. tetracycline in cats, caparsolate in dogs, acetaminophen. Certain drugs may decrease ALT (and AST) activity, by impairing activation of vitamin B6 to P5P, e.g. cephalosporin, cyclosporin, isoniazide.

  • Disease effects
    1) Liver disease: Both primary and secondary hepatic disease can cause increased ALT levels, if altered cell membrane permeability or necrosis occur. Usually ALT values exceed AST values in liver disease. Hepatic neoplasia can result in marked increases in ALT in dogs, although increases in AST are often higher than the increases in ALT. Bile duct obstruction will increase ALT (and AST) due to the toxic effects of retained bile salts on hepatocytes. Trauma will often increase ALT levels, even without morphologic evidence of cell injury.

    2) Muscle disease: In large animals, ALT will increase with muscle injury but is not more useful than AST in this regard so it is not included on large animal chemistry panels. In small animals with severe muscle injury (ischemic myopathy in cats, muscular dystrophy in dogs), ALT will increase with CK and AST. However, the increases in ALT are usually less than increases in AST in primary muscle disease and SDH values should be normal (unless there is concurrent liver injury).
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