The active form of vitamin D
3, 1
α,25-dihydroxyvitamin D
3 [1
α,25(OH)
2D
3], 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)
2D
3, many 1
α,25(OH)
2D
3 analogs have been synthesized to separate calcemic properties from the antiproliferative cell-differentiating properties. 1
α,25(OH)
2D
3 and its precursor, 25-hydroxyvitamin D
3 [25(OH)D
3], are metabolized
via C-24 and C-23/26 oxidation pathways. Recently, a novel A-ring modification metabolic pathway of 1
α,25(OH)
2D
3, the C-3 epimerization pathway, was identified. In our laboratory, C-3 epimerized metabolites of major natural vitamin D
3 metabolites, 1
α,25(OH)
2D
3, 25(OH)D
3 and 24,25-dihydroxyvitamin D
3 [24,25(OH)
2D
3], and a synthetic analog, 22-oxacalcitriol [22-oxa-1
α,25(OH)
2D
3, 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 D
3 [25-ene-22-oxa-1
α(OH)D
3] and 25-dehydroxy-24-ene-22-oxa-1
α-hydroxyvitamin D
3 [24-ene-22-oxa-1
α(OH)D
3]. In this mini-review, the identification of C-3 epimers of vitamin D
3 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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