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J.Health Sci., 49(4), 260-266, 2003
-Minireview-
Novel Metabolic Pathways of Vitamin
D3 - Identification of C-3 Epimerization and C-25
Dehydration Pathways and Biological Activity of Novel
Metabolites
Maya Kamao and Toshio Okano*
Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe
658-8558, Japan
The active form of vitamin D3,
1alpha,25-dihydroxyvitamin D3
[1alpha,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
1alpha,25(OH)2D3, many
1alpha,25(OH)2D3 analogs have been synthesized to
separate calcemic properties from the antiproliferative cell-differentiating properties.
1alpha,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
1alpha,25(OH)2D3, the C-3 epimerization pathway, was identified.
In our laboratory, C-3 epimerized metabolites of major natural vitamin
D3 metabolites,
1alpha,25(OH)2D3,
25(OH)D3 and 24,25-dihydroxyvitamin
D3 [24,25(OH)2D3], and a synthetic analog, 22-oxacalcitriol
[22-oxa-1alpha,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-1alpha-hydroxyvitamin
D3
[25-ene-22-oxa-1alpha(OH)D3] and
25-dehydroxy-24-ene-22-oxa-1alpha-hydroxyvitamin
D3
[24-ene-22-oxa-1alpha(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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