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

Vitamin B6-dependent enzymes, also known as pyridoxal 5'-phosphate (PLP)-dependent enzymes, represent a vast group of proteins that utilize the active form of vitamin B6 as a cofactor to catalyze essential biochemical reactions [1]. These enzymes are primarily involved in amino acid metabolism, including transamination, decarboxylation, and racemization, which are critical for the synthesis of neurotransmitters like GABA and dopamine, as well as heme and sphingolipids [2][3]. Due to their central role in physiology, specific members of this class are targeted by drugs to treat neurological disorders, bacterial infections, and metabolic diseases [4]. For instance, vigabatrin acts as a suicide inhibitor of GABA transaminase to treat epilepsy, while carbidopa inhibits DOPA decarboxylase to manage Parkinson's disease symptoms [5]. However, the high degree of structural conservation in the PLP-binding active site across more than 140 human enzymes poses a significant challenge for drug selectivity [4]. Therapeutic intervention often carries risks of off-target effects and systemic vitamin B6 depletion, which can lead to peripheral neuropathy and other neurotoxicities [6].

Other names

Vitamin B6-dependent enzymesB6-dependent enzymesPLP-dependent enzymesPyridoxal phosphate-dependent enzymes

Inhibition of the PLP-dependent catalytic cycle through competitive binding at the active site, formation of a stable external aldimine, or suicide inhibition (mechanism-based inactivation).