Alanine and Aspartate Aminotransferase (ALT, AST)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are intracellular enzymes that catalyse the transfer of an amino group from alanine or aspartate onto a keto acid, linking amino-acid and carbohydrate metabolism. When hepatocytes are injured the enzymes leak into the blood, so a rise in serum ALT and AST is the principal biochemical marker of hepatocellular injury and the most widely used pair in the liver panel.

Definition

ALT and AST are pyridoxal-phosphate-dependent aminotransferase enzymes whose serum activities rise when hepatocyte membranes are damaged; they are the standard biochemical indicators of hepatocellular injury within the liver panel.

Scope

The entry covers the biochemistry of the two transaminases, their tissue distribution and subcellular location, why their serum elevation marks hepatocyte injury rather than loss of function, and the interpretive role of the AST/ALT (De Ritis) ratio. It treats the markers as a clinical-biochemistry topic and is not guidance for interpreting an individual's results.

Core questions

• What biochemical reactions do ALT and AST catalyse, and where are the enzymes located in cells and tissues?
• Why does serum transaminase activity rise with hepatocellular injury rather than with loss of liver function?
• What does the AST/ALT (De Ritis) ratio add to interpretation?
• Why is ALT more liver-specific than AST?

Key concepts

• Transamination and pyridoxal-5'-phosphate cofactor
• ALT predominantly cytosolic; AST cytosolic and mitochondrial isoforms
• Enzyme leakage as the mechanism of serum elevation
• ALT relative liver specificity versus AST broad tissue distribution
• Hepatocellular injury pattern
• AST/ALT (De Ritis) ratio
• Upper limit of normal and sex-specific reference intervals

Mechanisms

Both enzymes catalyse reversible transamination, transferring an amino group to alpha-ketoglutarate to form glutamate, with pyridoxal-5'-phosphate (vitamin B6) as cofactor: ALT acts on alanine to yield pyruvate, AST on aspartate to yield oxaloacetate. ALT is largely cytosolic and concentrated in the liver, making it relatively liver-specific; AST exists as both cytosolic and mitochondrial isoenzymes and is abundant in liver, cardiac and skeletal muscle, kidney, and erythrocytes, so it is less specific. When hepatocyte plasma membranes are damaged the cytosolic enzymes leak into the circulation, and with more severe injury mitochondrial AST is also released. Because the rise reflects cell leakage, marked elevations indicate the extent of injury, not the liver's functional capacity. The ratio of AST to ALT, introduced by Fernando De Ritis, helps characterise the pattern of injury.

Clinical relevance

Serum ALT and AST are the most frequently used markers of liver-cell injury and a routine part of biochemical screening. This entry explains what the enzymes are and why their serum activity changes; it describes how these markers are generated and read at the level of biochemistry and patterns, and is not a basis for diagnosing or treating any individual.

Epidemiology

Mildly elevated aminotransferases are common in the general population and are frequently found incidentally in asymptomatic people, with metabolic dysfunction-associated fatty liver disease a leading correlate; population studies have examined how aminotransferase levels and the AST/ALT ratio relate to outcomes even within the conventional reference range.

Evidence & guidelines

Clinical guidance such as the American College of Gastroenterology guideline addresses how raised aminotransferases should be interpreted and worked up, and emphasises defining a true upper limit of normal; reviews and clinical-chemistry textbooks describe the enzymes and the De Ritis ratio.

History

Serum transaminase activity was developed as a clinical marker of tissue injury in the 1950s, when assays such as Karmen's spectrophotometric method made measurement practical; Fernando De Ritis and colleagues described the diagnostic value of the AST/ALT ratio in viral hepatitis in 1957, and the ratio still bears his name.

Debates

What is the correct upper limit of normal for ALT?

Conventional reference ranges may have been set using populations that included people with undetected fatty liver, leading to arguments that the upper limit of normal should be lowered and made sex-specific to improve sensitivity for liver disease.

Key figures

• Fernando De Ritis
• Arthur Karmen

Seminal works

• pratt-kaplan-2000
• kwo-2017

Frequently asked questions

Why is ALT considered more liver-specific than AST?

ALT is concentrated in the liver and is mainly cytosolic, whereas AST is also abundant in heart, skeletal muscle, kidney, and red blood cells, so a rise in AST can come from sources other than the liver.

What is the De Ritis ratio?

It is the ratio of AST to ALT activity, named after Fernando De Ritis; the relative values of the two enzymes are used to help characterise the pattern of liver injury.