标题：Novel Metabolic Pathways of Vitamin D3 — Identification of C-3 Epimerization and C-25 Dehydration Pathways and Biological Activity of Novel Metabolites
摘要：The active form of vitamin D3, 1 α ,25-dihydroxyvitamin D3 [1 α ,25(OH)2D3], functions to maintain calcium and phosphorus homeostasis and plays an important role in cell proliferation and differentiation. Since the discovery of non-classical functions of 1 α ,25(OH)2D3, many 1 α ,25(OH)2D3 analogs have been synthesized to separate calcemic properties from the antiproliferative cell-differentiating properties. 1 α ,25(OH)2D3 and its precursor, 25-hydroxyvitamin D3 [25(OH)D3], are metabolized via C-24 and C-23/26 oxidation pathways. Recently, a novel A-ring modification metabolic pathway of 1 α ,25(OH)2D3, the C-3 epimerization pathway, was identified. In our laboratory, C-3 epimerized metabolites of major natural vitamin D3 metabolites, 1 α ,25(OH)2D3, 25(OH)D3 and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], and a synthetic analog, 22-oxacalcitriol [22-oxa-1 α ,25(OH)2D3, OCT], were identified. In addition, other novel metabolites of OCT were assigned to two kinds of C-25 dehydrates, 25-dehydroxy-25-ene-22-oxa-1 α -hydroxyvitamin D3 [25-ene-22-oxa-1 α (OH)D3] and 25-dehydroxy-24-ene-22-oxa-1 α -hydroxyvitamin D3 [24-ene-22-oxa-1 α (OH)D3]. In this mini-review, the identification of C-3 epimers of vitamin D3 compounds and C-25 dehydrates of OCT using 1H-NMR and LC-MS techniques is described. Furthermore, the cell-specific generation and biological activity of these novel metabolites are reviewed.
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