Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1

The Journal of Steroid Biochemistry and Molecular Biology
Elaine W TieuRobert C Tuckey

Abstract

CYP11A1 hydroxylates vitamin D3 producing 20S-hydroxyvitamin D3 [20(OH)D3] and 20S,23-dihydroxyvitamin D3 [20,23(OH)2D3] as the major and most characterized metabolites. Both display immuno-regulatory and anti-cancer properties while being non-calcemic. A previous study indicated 20(OH)D3 can be metabolized by rat CYP24A1 to products including 20S,24-dihydroxyvitamin D3 [20,24(OH)2D3] and 20S,25-dihydroxyvitamin D3, with both producing greater inhibition of melanoma colony formation than 20(OH)D3. The aim of this study was to characterize the ability of rat and human CYP24A1 to metabolize 20(OH)D3 and 20,23(OH)2D3. Both isoforms metabolized 20(OH)D3 to the same dihydroxyvitamin D species with no secondary metabolites being observed. Hydroxylation at C24 produced both enantiomers of 20,24(OH)2D3. For rat CYP24A1 the preferred initial site of hydroxylation was at C24 whereas the human enzyme preferred C25. 20,23(OH)2D3 was initially metabolized to 20S,23,24-trihydroxyvitamin D3 and 20S,23,25-trihydroxyvitamin D3 by rat and human CYP24A1 as determined by NMR, with both isoforms showing a preference for initial hydroxylation at C25. CYP24A1 was able to further oxidize these metabolites in a series of reactions which included the cl...Continue Reading

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Jun 5, 2014·The FEBS Journal·Elaine W TieuRobert C Tuckey
Aug 21, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Chloe Y S ChengRobert C Tuckey

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Citations

Mar 13, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Chloe Y S ChengRobert C Tuckey
Feb 22, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Andrzej T SlominskiCraig A Elmets
May 23, 2020·Cell Biochemistry and Biophysics·Andrzej T SlominskiRobert C Tuckey
May 21, 2021·Clinical Chemistry and Laboratory Medicine : CCLM·Carl JenkinsonDavid J Handelsman

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