AminotransferasesEdit
Aminotransferases are a class of enzymes that catalyze transamination reactions, transferring amino groups between amino acids and α-keto acids. These reactions are central to the management of nitrogen in cells and to the interconversion of amino acids and metabolic intermediates. Because they depend on the cofactor pyridoxal phosphate, a form of vitamin B6, aminotransferases knit together amino acid metabolism with central carbon metabolism, linking nitrogen handling to energy production and biosynthesis. In humans, two aminotransferases are especially well known for their clinical significance: alanine aminotransferase and aspartate aminotransferase, often discussed in the context of liver health and metabolic disease. See transamination and pyridoxal phosphate for broader context, and note that these enzymes participate in networks involving substrates such as pyruvate, oxaloacetate, alpha-ketoglutarate, and the amino acids alanine and aspartate.
The activity of aminotransferases connects amino acid pools to the intermediates of energy metabolism. The general reaction most people encounter is reversible: an amino group is transferred from an amino acid to a keto acid, producing a new amino acid and a new keto acid. In human metabolism, the best-studied examples are the ALT-catalyzed transfer from alanine to alpha-ketoglutarate to form pyruvate and glutamate, and the AST-catalyzed transfer from aspartate to alpha-ketoglutarate to form oxaloacetate and glutamate. These transformations rely on the cofactor PLP in the active site and proceed through a series of intermediates that toggle the enzyme between different forms. For a broader framework, consider the concepts of enzyme catalysis and the role of PLP in many amino-transfer reactions.
Biochemistry
Chemistry and mechanism
Aminotransferases operate via a PLP-dependent mechanism in which the cofactor serves as an electron sink to stabilize carbanionic intermediates. The amino acid substrate forms an external aldimine with PLP, transfers its amino group to the cofactor, and ultimately yields a new amino acid and a new α-keto acid. The cycle regenerates the enzyme-bound PLP for subsequent rounds of catalysis. Because the reactions are reversible, the direction of transfer depends on substrate and product concentrations inside the cell. For a closer look at the molecular details, see pyridoxal phosphate and transamination.
Cofactor and substrates
PLP binds covalently to a lysine residue in the active site of aminotransferases, forming the resting internal aldimine. Substrate amino acids displace this lysine to form the external aldimine, which then undergoes rearrangements that relocate the amino group to the cofactor. After product release, PLP is restored to its resting form. The key substrates include the amino acids alanine and aspartate and the α-keto acids derived from them, namely pyruvate and oxaloacetate, as well as the cofactor's partner pathways involving alpha-ketoglutarate and glutamate.
Isozymes and localization
Humans express multiple isozymes of aminotransferases that differ in subcellular location and tissue distribution. In the case of alanine aminotransferase, the principal cytosolic form is GPT1, with a mitochondrial counterpart GPT2. For aspartate aminotransferase, GOT1 represents the cytosolic form, while GOT2 is mitochondrial. The subcellular localization influences how these enzymes participate in cytosolic versus mitochondrial metabolism and how they contribute to nitrogen handling and energy production across compartments.
Isozymes and localization
- Alanine aminotransferase (ALT): GPT1 (cytosolic) and GPT2 (mitochondrial). See alanine aminotransferase for broader discussion of function and tissue distribution.
- Aspartate aminotransferase (AST): GOT1 (cytosolic) and GOT2 (mitochondrial). See aspartate aminotransferase for additional context.
Clinical significance
Aminotransferases occupy a central place in clinical biochemistry because their presence in the bloodstream reflects cellular injury, particularly in the liver but also in other tissues. ALT is more liver-specific, while AST is found in liver as well as heart, muscle, kidney, and red blood cells, so elevations can reflect damage in multiple tissues. Serum levels of ALT and AST are commonly included in liver function test panels and are interpreted alongside other indicators of liver health, metabolism, and injury. See liver function tests for the broader diagnostic framework and De Ritis ratio for discussion of the typical AST/ALT ratio used in certain differential diagnoses.
- In hepatocellular injury (e.g., viral hepatitis, toxin-induced liver damage, non-alcoholic fatty liver disease), ALT often rises first and may be higher than AST, reflecting liver-specific release.
- In alcoholic liver disease, the AST:ALT ratio commonly exceeds 2:1, a pattern influenced by factors such as mitochondrial AST release and vitamin B6 status, but this ratio is not a definitive diagnostic marker and must be interpreted in the clinical context.
- Elevations can also arise from muscle disease, myocardial infarction, hemolysis, or certain medications, underscoring the need to consider tissue source and overall clinical picture.
Interpreting aminotransferase levels requires integration with other laboratory results and clinical information. Beyond diagnostics, aminotransferases illustrate how nucleotide and amino acid metabolism intersects with health, diet, and disease. See amino acid metabolism and liver function tests for related topics, and consider how changes in substrate availability or enzyme activity can shift metabolic balance.