Pyridoxal 5'-phosphate biosynthesis by pyridox-(am)-ine 5'-phosphate oxidase: species-specific features

Rivero, Maribel (Universidad de Zaragoza) ; Novo, Nerea ; Medina, Milagros (Universidad de Zaragoza)

Resumen: Enzymes reliant on pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5′-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5′-phosphate and pyridoxamine 5′-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms.

Idioma: Inglés

DOI: 10.3390/ijms25063174

Año: 2024

Publicado en: International Journal of Molecular Sciences 25, 6 (2024), 3174 [23 pp.]
ISSN: 1661-6596

Financiación: info:eu-repo/grantAgreement/ES/DGA/E35-23R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-136369NB-I00

Tipo y forma: Revisión (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)