ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.The Journal of investigative dermatology · 2024Review
- Review
- Article
- Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System.Nutrients · 2022Review
- Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy.International journal of molecular sciences · 2022Review
- CYP11A1‑derived vitamin D hydroxyderivatives as candidates for therapy of basal and squamous cell carcinomas.International journal of oncology · 2022Article
- Chemical synthesis, biological activities and action on nuclear receptors of 20S(OH)DBioorganic chemistry · 2022Article
- Vitamin D: A Potential Star for Treating Chronic Pancreatitis.Frontiers in pharmacology · 2022Review
- Simultaneous measurement of 13 circulating vitamin D3 and D2 mono and dihydroxy metabolites using liquid chromatography mass spectrometry.Clinical chemistry and laboratory medicine · 2021Article
- Vitamin D and lumisterol derivatives can act on liver X receptors (LXRs).Scientific reports · 2021Article
- Detection of 7-Dehydrocholesterol and Vitamin D3 Derivatives in Honey.Molecules (Basel, Switzerland) · 2020Article
- Photoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives.Cell biochemistry and biophysics · 2020Review
- The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers.Advances in experimental medicine and biology · 2020Review
- The serum vitamin D metabolome: What we know and what is still to discover.The Journal of steroid biochemistry and molecular biology · 2019Review
- Human cytochrome P450 enzymes 5-51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition - toxic effects and benefits.Drug metabolism reviews · 2018Review
- Properties of purified CYP2R1 in a reconstituted membrane environment and its 25-hydroxylation of 20-hydroxyvitamin D3.The Journal of steroid biochemistry and molecular biology · 2018Article
- On the role of classical and novel forms of vitamin D in melanoma progression and management.The Journal of steroid biochemistry and molecular biology · 2018Review
- Investigation of 20S-hydroxyvitamin DScientific reports · 2018Article
- Endogenously produced nonclassical vitamin D hydroxy-metabolites act as "biased" agonists on VDR and inverse agonists on RORα and RORγ.The Journal of steroid biochemistry and molecular biology · 2017Review
- Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management.Laboratory investigation; a journal of technical methods and pathology · 2017Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
CYP11A1 can hydroxylate vitamin D3 at carbons 17, 20, 22, and 23, producing a range of secosteroids which are biologically active with respect to their ability to inhibit proliferation and stimulate differentiation of various cell types, including cancer cells. As 1α-hydroxylation of the primary metabolite of CYP11A1 action, 20S-hydroxyvitamin D3 [20(OH)D3], greatly influences its properties, we examined the ability of both human and mouse CYP27B1 to 1α-hydroxylate six secosteroids generated by CYP11A1. Based on their kcat/Km values, all CYP11A1-derived metabolites are poor substrates for CYP27B1 from both species compared with 25-hydroxyvitamin D3. No hydroxylation of metabolites with a 17α-hydroxyl group was observed. 17α,20-Dihydroxyvitamin D3 acted as an inhibitor on human CYP27B1 but not the mouse enzyme. We also tested CYP27B1 activity on 20,24-, 20,25-, and 20,26-dihydroxyvitamin D3, which are products of CYP24A1 or CYP27A1 activity on 20(OH)D3. All three compounds were metabolized with higher catalytic efficiency (kcat/Km) by both mouse and human CYP27B1 than 25-hydroxyvitamin D3. CYP27B1 action on these new dihydroxy derivatives was confirmed to be 1α-hydroxylation by mass spectrometry and nuclear magnetic resonance analyses. Both 1,20,25- and 1,20,26- trihydroxyvitamin D3 were tested for their ability to inhibit melanoma (SKMEL-188) colony formation, and were significantly more active than 20(OH)D3. This study shows that CYP11A1-derived secosteroids are 1α-hydroxylated by both human and mouse CYP27B1 with low catalytic efficiency, and that the presence of a 17α-hydroxyl group completely blocks 1α-hydroxylation. In contrast, the secondary metabolites produced by subsequent hydroxylation of 20(OH)D3 at C24, C25, or C26 are very good substrates for CYP27B1.
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