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chemicals
Table of Contents
(25R)-27(OH)L3, (25S)-27(OH)L3, 22(OH)L3, 24(OH)L3, 25(OH)L3 and 20,22(OH)₂L3 were prepared enzymatically from the L3 substrate and purified as described previously [21, 24]. 20S(OH)7-DHC and 20S(OH)L3 are synthesized by chemical methods [26]. The chemical synthesis and purification methods of 20S, 23S(OH)₂D₃, 20S, 25(OH)₂D₃ and 20S(OH)D₃ are detailed in [27]. L3, 1α,25(OH)₂D₃, 25(OH)D₃, 7-DHC, and 20S(OH)cholesterol were purchased from Toronto Research Chemicals (north York, Ontario, canada).
Generation of L3 hydroxy metabolites in vivo
We have previously reported that CYP11A1 can convert L3 to different metabolites in vitro [21]; these metabolites were also detected in human serum and epidermis, and also in cultured keratinocytes [15]. We also found that 20S(OH)L3 is another product of CYP11A1 acting on L3. We also demonstrated the enzymatic activity of CYP27A1 on L3, the most important metabolites of which are 25(OH)L3, (25R)-27(OH)L3 and (25S)-27(OH)L3 [24]. In this study, we further detected 25(OH)L3.
Discussion
Although the role of vitamin D₃ in maintaining body homeostasis has been widely recognized, the biological function of its photoderivative L3 is gradually being recognized.L3 can be efficiently metabolized by CYP27A1 into biologically active hydroxyphotosterols, including (25R)-27(OH)L3, (25S)-27(OH)L3 and 25(OH)L3. In addition, 7-dehydrocholesterol reductase (DHCR7) does not act on L3 and its hydroxy metabolites, but only on its stereoisomer 7-DHC. in this study, we build on previous research and find…
Artificial Intelligence Statement
The authors did not use artificial intelligence in the scientific writing process.
andrzej T. Slominski: Responsible for writing, review and editing, original draft writing, project supervision, resource coordination, grant application, data analysis, and concept development.
Tae-Kang Kim: Responsible for writing, review and editing, methodological design, experimental conduct and data management.
Zorica Janjetovic: Responsible for writing, review and editing, project supervision, methodological design, experimental implementation and data management.
Senthilkumar Ravichandran: Responsible for writing, review and editing, methodological design, experimental conduct and data management.
Yuwei Song: Responsible for writing…
Funding
This research was supported by NIH project R01AR071189. We also received support from the NIH (R01AR073004) project, VA merit award (I01BX004293) for ATS, and NIH (R01AG068395 and R01AG081228) for YS.in addition,funding was received from the National Institute of Environmental Health Sciences (NIH) Intramural research Program (Z01 ES102005 and Z01ES101585). NIH authors’ contributions are made as part of their official duties as federal employees and consistent with agency