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• W2148934222 abstract "Recently, we demonstrated that some A-ring-modified vitamin D₃ analogs had unique biological activity. Of these analogs, 2α-propoxy-1α,25(OH)₂D₃ (C3O1) and 2α-(3-hydroxypropoxy)-1α,25(OH)₂D₃ (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the <i>K</i>_m and <i>k</i>_cat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1α,25(OH)₂D₃. Thus, the catalytic efficiency, <i>k</i>_cat/<i>K</i>_m, of human CYP24A1 for O2C3 is only 2% of 1α,25(OH)₂D₃. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis." @default.
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• W2148934222 date "2005-03-11" @default.
• W2148934222 modified "2023-10-16" @default.
• W2148934222 title "METABOLISM OF 2α-PROPOXY-1α,25-DIHYDROXYVITAMIN D₃AND 2α-(3-HYDROXYPROPOXY)-1α,25-DIHYDROXYVITAMIN D₃BY HUMAN CYP27A1 AND CYP24A1" @default.
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• W2148934222 doi "https://doi.org/10.1124/dmd.104.003038" @default.
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