Mechanism and Biological Role
Transamination is an exchange reaction that proceeds without the direct consumption of ATP. The primary amino group donors in cells are glutamate, aspartate, and alanine. This process is most active in the liver, although it occurs in all tissues of the body.
In metabolism, transamination fulfills two opposing tasks:
- Anabolic (synthesis): Formation of non-essential amino acids during local deficiency. The amino group is simply transferred to a carbon skeleton counterpart (the corresponding $\alpha$-keto acid), ensuring the redistribution of amino nitrogen.
- Catabolic (breakdown): Transamination serves as the first step in amino acid degradation. Removal of the amino group leaves a carbon skeleton in the form of an $\alpha$-keto acid, which is subsequently oxidized in the citric acid cycle to generate energy or used for glucose synthesis (gluconeogenesis) and ketone bodies.
Aminotransferase Enzymes (ALT and AST)
These reactions are catalyzed by specific intracellular enzymes known as aminotransferases (transaminases). There are over 10 variants of these enzymes, all requiring the coenzyme pyridoxal phosphate (a derivative of vitamin $B_6$).
Two enzymes are of greatest clinical significance:
- Alanine aminotransferase (ALT): Catalyzes the transfer of an amino group between alanine and $\alpha$-ketoglutarate, yielding pyruvate and glutamate.
- Aspartate aminotransferase (AST): Catalyzes the reaction between aspartate and $\alpha$-ketoglutarate, synthesizing oxaloacetate and glutamate.
AST exists in two isoforms: cytosolic (c-AST) and mitochondrial (m-AST). In hepatocytes and myocardial cells, the mitochondrial fraction accounts for up to 80% of the enzyme activity.
Principles of Enzyme Diagnostics
Normally, aminotransferases function intracellularly, so their activity in serum is minimal (5–40 U/L). When the cell membrane is damaged (cytolysis syndrome), these enzymes spill into the bloodstream in large quantities. Because transaminases are organ-specific, their serum levels help localize pathology.
- Liver pathology (viral hepatitis): The key marker is a sharp increase in ALT (6- to 8-fold). The peak is observed on days 2–3, and normalization is slow (taking over 15 days).
- Myocardial infarction: Characterized by a pronounced elevation of AST (8-to 10-fold) against a background of a minor rise in ALT. Note: Angina pectoris or valvular heart disease does not cause elevated transaminase activity.
De Ritis Ratio
For differential diagnosis, clinicians use the De Ritis ratio—the ratio of serum AST activity to ALT activity.
| State | Ratio | Explanation |
|---|---|---|
| Normal | $1.33 \pm 0.42$ | Physiological enzyme ratio |
| Acute hepatitis | Decreased ($\approx 0.6$) | Dominant release of ALT due to liver parenchymal damage |
| Liver cirrhosis | Approaches $1.0$ | Severe necrosis leads to the release of heavy mitochondrial AST fraction |
| Myocardial infarction | Increased (up to $6.0$) | Massive release of heart-specific AST |
Additional markers often used for liver pathology include $\gamma$-glutamyl transferase ($\gamma$-GT), which reflects cholestasis and toxic injury, while specific isoforms of creatine kinase (CK-MB) and lactate dehydrogenase (LDH-1) are used for myocardial injury.