PNPO Human

Pyridoxamine 5’-Phosphate Oxidase (PNPO) is an enzyme that plays a crucial role in the metabolism of vitamin B6. It is classified under the enzyme class oxidases, specifically oxidoreductases, which catalyze oxidation-reduction reactions. The enzyme is encoded by the PNPO gene and is responsible for the biosynthesis of pyridoxal 5’-phosphate (PLP), the active form of vitamin B6 .

PNPO catalyzes the final, rate-limiting step in the vitamin B6 metabolism pathway. This step involves the conversion of pyridoxine 5’-phosphate (PNP) and pyridoxamine 5’-phosphate (PMP) into pyridoxal 5’-phosphate (PLP). PLP is an essential cofactor for various enzymatic reactions, including amino acid metabolism, neurotransmitter synthesis, and hemoglobin production .

PNPO is a homodimer, meaning it consists of two identical polypeptide subunits. Each subunit binds one molecule of PLP. The enzyme’s structure includes both alpha-helices and beta-sheets, forming a split-barrel motif. Disulfide bonds and salt-bridge interactions stabilize the dimeric structure. The enzyme also requires a cofactor, flavin mononucleotide (FMN), which is held in place by hydrogen-bond interactions within a deep cleft formed by the two polypeptide subunits .

The enzyme’s active site undergoes conformational changes during the catalytic process. In the absence of PLP, the active site is in an “open” conformation. Upon substrate binding and conversion to PLP, the active site partially closes. Specific amino acid residues form hydrogen bonds with PLP, creating a “closed” conformation that stabilizes the enzyme-substrate complex .

PNPO activity is regulated by the availability of its substrates (PNP and PMP) and the cofactor FMN. The enzyme’s expression is also influenced by the cellular demand for PLP, which varies depending on metabolic needs and physiological conditions .

Mutations in the PNPO gene can lead to PNPO deficiency, a rare metabolic disorder characterized by seizures, developmental delay, and other neurological symptoms. This condition results from impaired PLP synthesis, leading to disrupted vitamin B6 metabolism and reduced availability of this essential cofactor .

Recombinant PNPO is used in research to study vitamin B6 metabolism and its associated disorders. It is also employed in the development of therapeutic strategies for conditions resulting from PNPO deficiency and other metabolic abnormalities .