Vitamin B6 is essential for serine de novo biosynthesis

• DOI: 10.1007/s10545-017-0061-3
• Publication Date: 2017-08-11T07:30:22Z
• Authors: Rúben J. Ramos; Mia L. Pras‐Raves; Johan Gerrits; Maria van der Ham; Marcel Willemsen; Hubertus Prinsen; Boudewijn Burgering; Judith J. Jans; Nanda M. Verhoeve...
• Keywords: Human genetics

Abstract Pyridoxal 5′‐phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor numerous enzyme reactions. PLP deficiency brain, either genetic or acquired, results severe drug‐resistant seizures that respond to B6 supplementation. The pathogenesis is largely unknown. To shed more light on metabolic consequences we performed untargeted metabolomics B6‐deprived Neuro‐2a cells. Significant alterations were observed range metabolites. most surprising observation was decrease serine and glycine, two amino acids are known be elevated plasma deficient patients. investigate cause low concentrations flux analysis biosynthesis performed. showed de novo synthesis significantly reduced In addition, formation glycine 5‐methyltetrahydrofolate decreased. Thus, for neuronal cells, critical maintain intracellular glycine. These findings suggest may patients with responsive epilepsy. 5‐mTHF vitro explain favourable but so far unexplained response some pyridoxine‐dependent epilepsy folinic acid