ビタミンD_3の新しい代謝経路に関する研究 : 3位水酸基異性体および25位脱水体代謝物の同定とその生物活性

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It is well established that the active form of vitamin D_3, 1α, 25-dihydroxyvitamin D_3[1a, 25(OH)_2D_3], is metabolized through C-24 and C-23/26 oxidation pathways. Recently, we identified novel 1α, 25(OH)_2D_3 metabolite, 3-epi-1α, 25(OH)_2D_3, in which C-3 hydroxyl group is epimerized from the β to the α position. It was also demonstrated that the natural vitamin D3 metabolites, 25-hydiroxyvitamin D_3 [25 (OH)D_3], 24R, 25-dihydroxyvitamin D_3 [24,25(OH)_2D_3] and a synthetic analog, 22-oxacalcitriol [22-oxa-1α, 25(OH)_2D_3, OCT] are metabolized via the C-3 epimerization pathway. 3-epi-1α, 25(OH)_2D_3, is further metabolized to C-24 hydroxide, 3-epi-1α, 24, 25(OH)_3, D_3. In addition, 3-epi-25 (OH)D_3, is metabolized to both C-1α hydroxide, 3-epi-1α, 25(OH)_2D_3, and C-24 hydroxide, 3-epi-24, 25(OH)_2D_3, like-wise 25(OH)D_3. The other novel metabolites of OCT were identified as two kinds of C-25 dehydrates, 25-dehydroxy-25-ene-22-oxa-1α-hydroxyvitamin D_3[25-ene-22-oxa-1α(OH)D_3] and 25-dehydroxy-24-ene-22-oxa-1α-hydroxyvitamin D_3 [24-ene-22-oxa-1α(OH)D_3]. The differences existed in the production rate of C-3 epimers and C-25 dehydrates with different cell types. The biological activity ofthese metabolites is lower than that of their substrate compounds.
2004-02-25