{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T06:53:27Z","timestamp":1773557607582,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Metakids foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pyridoxal 5\u2032\u2010phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug\u2010resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6\u2010deprived Neuro\u20102a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the <jats:italic>de novo<\/jats:italic> synthesis of serine was significantly reduced in vitamin B6\u2010deprived cells. In addition, formation of glycine and 5\u2010methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine <jats:italic>de novo<\/jats:italic> biosynthesis in neuronal cells, and serine <jats:italic>de novo<\/jats:italic> synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5\u2010mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine\u2010dependent epilepsy to folinic acid supplementation.<\/jats:p>","DOI":"10.1007\/s10545-017-0061-3","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T07:30:22Z","timestamp":1502436622000},"page":"883-891","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Vitamin B6 is essential for serine <i>de novo<\/i> biosynthesis"],"prefix":"10.1002","volume":"40","author":[{"given":"R\u00faben J.","family":"Ramos","sequence":"first","affiliation":[{"name":"Section Metabolic Diagnostics, Department of Genetics University Medical Center Utrecht KC02.069.1, Lundlaan 6 Utrecht 3584 EA The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia 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