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).
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
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