Pyridoxal Phosphate-Dependent Enzymes (None)

Pyridoxal phosphate-dependent enzymes (PLP-dependent enzymes) are a large and diverse class of enzymes that require pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, as a cofactor. These enzymes are found in all domains of life and catalyze a wide variety of chemical reactions, primarily involving amino acids and amines. PLP-dependent enzymes play essential roles in metabolism, particularly in amino acid metabolism, catalyzing reactions such as transamination, decarboxylation, and deamination. Clinically relevant targets include DOPA decarboxylase (Parkinson's disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (cancer/malaria), ornithine decarboxylase (African sleeping sickness/cancer), alanine racemase (antibacterial target).

Formation of an internal aldimine between PLP’s aldehyde group and an active site lysine residue on the enzyme. Upon substrate binding, this linkage is replaced by an external aldimine with the substrate’s amino group. PLP acts as an electron sink to stabilize carbanionic intermediates during catalysis.