Aminotransferases and other PLP-dependent enzymes (PLP-dependent enzymes)

Aminotransferases and other PLP-dependent enzymes constitute a large family of enzymes that utilize pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, as an essential cofactor for catalysis (NIH, 2021). These enzymes are primarily involved in amino acid metabolism and the biosynthesis of biogenic amines and neurotransmitters, such as GABA, dopamine, and serotonin (PubMed, 2019). They catalyze a wide array of reactions, including transamination, decarboxylation, and racemization, by acting as an "electron sink" to stabilize carbanionic intermediates (Frontiers in Molecular Biosciences, 2019). Several members of this class are validated therapeutic targets; for instance, GABA aminotransferase is targeted by vigabatrin for epilepsy, and DOPA decarboxylase is inhibited by carbidopa in Parkinson's disease (StatPearls, 2023). Many drugs targeting these enzymes are mechanism-based "suicide" inhibitors that form irreversible covalent bonds with the PLP cofactor (Journal of Biological Chemistry, 2022). However, pharmacological interference with PLP-dependent pathways can lead to safety concerns such as peripheral neuropathy and vitamin B6 deficiency (PubMed, 2020). Additionally, aminotransferases like ALT and AST serve as critical clinical biomarkers for liver function and systemic health (NIH, 2023). The diversity of this enzyme class makes it a rich source for drug discovery, particularly in oncology and infectious diseases where specific metabolic pathways are upregulated (RSC, 2023).

Other names

Vitamin B6-dependent enzymesPLP-dependent enzyme familyTransaminases and other PLP-dependent enzymes

Suicide inhibition (covalent inactivation of the PLP-enzyme complex), competitive inhibition, and sequestration of the PLP cofactor.