Chemical Synthesis of Side-Chain-Hydroxylated Vitamin D3 Derivatives and Their Metabolism by CYP27B1 |
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| Authors: | Ryota Sakamoto Akiko Nagata Haruki Ohshita Yuka Mizumoto Miho Iwaki Dr Kaori Yasuda Prof Toshiyuki Sakaki Dr Kazuo Nagasawa |
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| Affiliation: | 1. Department of Biotechnology and Life Science, Graduate School of Technology, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, 184-8588 Tokyo, Japan;2. Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398 Japan |
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| Abstract: | 1α,25-Dihydroxyvitamin D3 (abbreviated here as 1,25D3) is a hormonally active form of vitamin D3 (D3), and is produced from D3 by CYP27 A1-mediated hydroxylation at C25, followed by CYP27B1-mediated hydroxylation at C1. Further hydroxylation of 25D3 and 1,25D3 occurs at C23, C24 and C26 to generate corresponding metabolites, except for 1,25R,26D3. Since the capability of CYP27B1 to hydroxylate C1 of side-chain-hydroxylated metabolites other than 23S,25D3 and 24R,25D3 has not been examined, we have here explored the role of CYP27B1 in the C1 hydroxylation of a series of side-chain-hydroxylated D3 derivatives. We found that CYP27B1 hydroxylates the R diastereomers of 24,25D3 and 25,26D3 more effectively than the S diastereomers, but shows almost no activity towards either diastereomer of 23,25D3. This is the first report to show that CYP27B1 metabolizes 25,26D3 to the corresponding 1α-hydroxylated derivative, 1,25,26D3. It will be interesting to examine the physiological relevance of this finding. |
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| Keywords: | CYP27B1 vitamin D3 metabolites 23 25-dihydroxyvitamin D3 24 25-dihydroxyvitamin D3 25 26-dihydroxyvitamin D3 |
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