Pyridoxal 5′-phosphate-dependent enzymes (PLP-dependent enzymes)

Pyridoxal 5′-phosphate (PLP)-dependent enzymes are a vast group of enzymes that utilize the active form of Vitamin B6 as an essential cofactor to catalyze diverse biochemical reactions, including transamination, decarboxylation, and racemization (Source: UniProt; PMID: 21803626). These enzymes play a fundamental role in the metabolism of amino acids and the biosynthesis of critical signaling molecules such as neurotransmitters (GABA, serotonin, dopamine) and heme (Source: StatPearls, Vitamin B6). Because of their central metabolic roles, specific PLP-dependent enzymes are targeted by various drugs; for example, Vigabatrin inhibits GABA aminotransferase to treat epilepsy, while Carbidopa inhibits DOPA decarboxylase to manage Parkinson's disease (Source: PubChem). A major challenge in targeting these enzymes is achieving selectivity, as many drugs can inadvertently react with the PLP cofactor itself or inhibit off-target PLP-dependent enzymes, leading to side effects like peripheral neuropathy or systemic Vitamin B6 deficiency (Source: NIH Office of Dietary Supplements). Consequently, therapeutic strategies often involve monitoring PLP levels or co-administering Vitamin B6 to mitigate these risks.

Other names

Vitamin B6-dependent enzymesPLP enzymesPyridoxal phosphate-dependent enzymes

Inhibition of specific PLP-dependent enzymes through covalent modification of the PLP-internal aldimine, formation of stable adducts with the cofactor, or competitive substrate inhibition.