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Unique 24-Hydroxylated Metabolites Represent a Significant Pathway of Metabolism of Vitamin D₂ in Humans: 24-Hydroxyvitamin D₂ and 1,24-Dihydroxyvitamin D₂ Detectable in Human Serum¹

University Department of Medicine, Manchester Royal Infirmary, (E.B.M., M.D., P.E.S.), Manchester; and the Department of Clinical Biochemistry, St. Bartholomew’s and the Royal London School of Medicine and Dentistry (H.L.J.M., N.J.S.), London, United Kingdom; the Department of Biochemistry, Queen’s University (G.J., V.B.), Kingston, Ontario, Canada; and Bone Care International (C.W.B., J.C.K.), Madison, Wisconsin 53713

Address all correspondence and requests for reprints to: Prof. E. B. Mawer, Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom M13 9WL.

We have produced evidence for a new metabolic pathway for vitamin D₂ in humans involving the production of 24-hydroxyvitamin D₂ (24OHD₂) and 1,24-dihydroxyvitamin D₂ [1,24-(OH)₂D₂]. These metabolites were produced after either a single large dose (10⁶ IU) of vitamin D₂ or repeated daily doses between 10³ and 5 x 10⁴ IU. We developed assay systems for the metabolites in human serum and showed that in some chronically treated patients, the concentration of 1,24-(OH)₂D₂ equalled that of 1,25-(OH)₂D₂ at about 100 pmol/L. The metabolites were identified by high performance liquid chromatography with diode array spectrophotometry for 24OHD₂ and by high resolution gas chromatography-mass spectrometry for 1,24-(OH)₂D₂. We show that 1,24-(OH)₂D₂ synthesis can be stimulated by PTH, indicating a renal origin for this metabolite and postulate that it is formed from 24OHD₂, which may be synthesized in liver. We conclude from this study that vitamin D₂ gives rise to two biologically active products, 1,24-(OH)₂D₂ and 1,25-(OH)₂D₂, and that 1,24-(OH)₂D₂ could be an attractive naturally occurring analog of 1,25-(OH)₂D₃ for clinical use.

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