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In mammals, PLP is primarily synthesized via a salvage pathway involving pyridoxal kinase (PLK), pyridoxine\/pyridoxamine 5\u2032\u2010phosphate oxidase (PNPO), and pyridoxal phosphate phosphatase (PLPP). However, recent evidence suggests the presence of additional, yet unidentified, enzymatic contributors to this pathway. Here, we identify aldo\u2010keto reductase family 1 member C (AKR1C) isozymes as previously unrecognized enzymes involved in vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    metabolism. We demonstrate that AKR1Cs catalyze two novel reactions: an NADPH\u2010dependent pyridoxal reductase (PLR) activity that converts pyridoxal (PL) to pyridoxine (PN), and an NADP\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent pyridoxal dehydrogenase (PLD) activity that oxidizes PL to 4\u2010pyridoxolactone (4\u2010PLA). Both reactions occur under physiological conditions and significantly impact intracellular vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    vitamer profiles. Moreover, we show that elevated PL levels suppress AKR1C activities toward non\u2010B\n                    <jats:sub>6<\/jats:sub>\n                    substrates, indicating reciprocal cross\u2010talk between vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    metabolism and other AKR1C\u2010dependent metabolic processes. This study expands the current framework of mammalian vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    metabolism, highlighting AKR1Cs as metabolic hubs with broad regulatory implications.\n                  <\/jats:p>","DOI":"10.1111\/febs.70471","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:19:43Z","timestamp":1772965183000},"page":"4841-4859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A new branch of mammalian vitamin B\n                    <sub>6<\/sub>\n                    metabolism:\n                    <scp>AKR1C<\/scp>\n                    \u2010mediated conversion of pyridoxal to pyridoxine and 4\u2010pyridoxolactone"],"prefix":"10.1111","volume":"293","author":[{"given":"Nayu","family":"Kito","sequence":"first","affiliation":[{"name":"Department of Applied Biosciences, Graduate School of Bioagricultural Sciences Nagoya University  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Kitaura","sequence":"additional","affiliation":[{"name":"Department of Food and Nutritional Sciences, College of Bioscience and Biotechnology Chubu University  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoka","family":"Iino","sequence":"additional","affiliation":[{"name":"Schizophrenia Research Project, Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Toriumi","sequence":"additional","affiliation":[{"name":"Schizophrenia Research Project, Department of Clinical Medical Sciences, Tokyo Metropolitan Institute of Medical Science  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunah","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Applied Biosciences, Graduate School of 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