Pyridoxine 5'-phosphate oxidase (PNPO)

Pyridoxine 5'-phosphate oxidase is a homodimeric, FMN-dependent oxidoreductase enzyme that catalyzes the final, rate-limiting step in the biosynthesis of pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6. It oxidizes both pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate to PLP, which is an essential cofactor for numerous enzymatic reactions, particularly in amino acid and neurotransmitter metabolism. Deficiency of this enzyme, usually due to genetic mutations in the PNPO gene, leads to reduced PLP levels, causing severe neurological disorders such as neonatal epileptic encephalopathy. The enzyme has a highly conserved structure with distinct species-specific regulatory features and operates via a tightly regulated catalytic cycle affecting PLP homeostasis. There are no known drugs that directly modulate PNPO, but PLP supplementation is the accepted treatment in deficiency states.

Other names

Pyridoxamine 5'-phosphate oxidasePyridoxamine (pyridoxine) 5′-phosphate oxidasePNPOx

Oxidation of pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate to form active pyridoxal 5'-phosphate, a coenzyme participating in numerous metabolic reactions