Aminotransferases

AMINOTRANSFERASES Definition – Interconversion of amino acids to 2-oxo-acids – Amino group donor – Amino group acceptor Aminotransferases of clinical interest Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)

Distribution – In serum Apoenzymes (Coenzyme-deficient) Holoenzymes – In tissues Throughout the body AST – Primarily » Heart, liver, skeletal muscle, and kidney – Forms » Mitochondrial » Cytoplasmic ALT – Primarily » Liver and kidney – Exclusively cytoplasmic

Tissue distribution

ALT is the more liver-specific enzyme Elevations of ALT activity persist longer than do those of AST activity

Clinical Significance Liver disease – The most important cause – Tenfold to fortyfold elevations of AST and ALT Viral hepatitis Acute hepatic necrosis – To diagnose chronic hepatitis Persistence of increased ALT for more than 6 months Most have maximum ALT less than seven times the upper reference

Clinical Significance Toxic hepatitis Acetaminophen-induced hepatic injury Transaminase 85 times the upper reference limit in 90% of case – AST and ALT » Peak early and fall rapidly

Carcinoma of the liver – Twofold to fivefold elevations – AST usually being higher than ALT Various medications – Slight or moderate elevations of both AST and ALT Less common causes – Hemochromatosis – Wilson's disease – Autoimmune hepatitis – Primary biliary cirrhosis – α 1 -antitrypsin deficiency

Clinical Significance Increased AST activity – AMI – Progressive muscular dystrophy Up to eight times normal With serum CK Mitochondrial AST (m-AST) – Extensive liver cell degeneration and necrosis – Ratio between m-AST and total AST Typical of alcoholic hepatitis Macro-AST – No known clinical relevance

Methods for the Measurement of Transaminase Activity The assay system – Two amino acids and two oxo-acids Formation or consumption of the oxo-acids is measured Various photometric substrates and dyes coupled to the transaminase reactions – Continuous-monitoring methods Transaminase reactions Oxo-acids formed Dehydrogenase reactions Reduction to hydroxy acids Change in NADH

Supplementation with P-5' –p NADH,MD or LD, must be present in sufficient quantity A preliminary incubation – Endogenous oxo-acids AST activity in serum – Up to 48 hours at 4°C – Frozen if they are to be kept longer ALT activity should be assayed on the day of sample collection

ALT stability – at -70°C. Hemolyzed specimens Reference Intervals – AST (upper reference limits for adults) 31 U/L for women 35 U/L for men – ALT 34 U/L 45 U/L

m-AST – 5% to I0% of the activity of total AST in serum – Reference limit 3.0 U/L