Pyridoxal 5'-phosphate-dependent aminotransferase (PLP-AT) (PLP-AT)

Pyridoxal 5'-phosphate (PLP)-dependent aminotransferases are a superfamily of enzymes that catalyze the reversible transfer of an amino group from an amino acid to an alpha-keto acid, a process central to amino acid metabolism and nitrogen homeostasis (PMID: 21906013). These enzymes require the active form of Vitamin B6, pyridoxal 5'-phosphate, which forms a covalent Schiff base with a conserved lysine residue in the active site to facilitate catalysis (UniProt: P04181). In the central nervous system, specific aminotransferases like 4-aminobutyrate aminotransferase (GABA-T) regulate the levels of the inhibitory neurotransmitter GABA, making them critical targets for antiepileptic therapy (PubMed: 11518334). Clinically, the leakage of intracellular aminotransferases such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) into the bloodstream serves as a primary biomarker for hepatocellular damage and myocardial infarction (StatPearls: Aminotransferases). Drugs like vigabatrin act as suicide inhibitors by binding irreversibly to the enzyme, while others like isoniazid can cause systemic PLP deficiency by forming hydrazones with the cofactor, leading to side effects like peripheral neuropathy (PubChem: Vigabatrin; NIH: LiverTox). Emerging research also highlights the role of branched-chain aminotransferases (BCAT) in promoting tumor growth, positioning this enzyme class as a potential target in oncology (PMID: 25159112). Bacterial versions of these enzymes are also investigated as targets for novel antibiotics, particularly in treating multidrug-resistant tuberculosis (PubMed: 26434146). Overall, this enzyme class represents a vital intersection of primary metabolism, clinical diagnostics, and diverse therapeutic interventions.

Other names

TransaminaseAminotransferasePLP-dependent enzymeAmino acid aminotransferase

Irreversible suicide inhibition of the enzyme active site, competitive inhibition of substrate binding, or depletion/antagonism of the essential PLP cofactor.