title: CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo.
abstract: Bioactivation of vitamin D consists of two sequential hydroxylation steps to produce 1α,25-dihydroxyvitamin D3. It is clear that the second or 1α-hydroxylation step is carried out by a single enzyme, 25-hydroxyvitamin D 1α-hydroxylase CYP27B1. However, it is not certain what enzyme or enzymes are responsible for the initial 25-hydroxylation. An excellent case has been made for vitamin D 25-hydroxylase CYP2R1, but this hypothesis has not yet been tested. We have now produced Cyp2r1 (-/-) mice. These mice had greater than 50% reduction in serum 25-hydroxyvitamin D3. Curiously, the 1α,25-dihydroxyvitamin D3 level in the serum remained unchanged. These mice presented no health issues. A double knockout of Cyp2r1 and Cyp27a1 maintained a similar circulating level of 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. Our results support the idea that the CYP2R1 is the major enzyme responsible for 25-hydroxylation of vitamin D, but clearly a second, as-yet unknown, enzyme is another contributor to this important step in vitamin D activation.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, WI 53706.
authors.forename: Jinge G
authors.initials: JG
authors.lastname: Zhu
authors.forename: Justin T
authors.initials: JT
authors.lastname: Ochalek
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Glenville
authors.initials: G
authors.lastname: Jones
authors.forename: Hector F
authors.initials: HF
authors.lastname: Deluca
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D053493:Cholestanetriol 26-Monooxygenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004838:Epiphyses / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D016678:Genome / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010758:Phosphorus / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D060888:Real-Time Polymerase Chain Reaction; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood
chemical_list: D012333:RNA, Messenger; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D010758:Phosphorus; C104450:25-hydroxyvitamin D; D008156:Luciferases; C569548:Cyp2r1 protein, mouse; D053493:Cholestanetriol 26-Monooxygenase; C506832:Cyp27a1 protein, mouse; D002118:Calcium
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