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Publication : CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo.

First Author  Zhu JG Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  39 Pages  15650-5
PubMed ID  24019477 Mgi Jnum  J:223194
Mgi Id  MGI:5648182 Doi  10.1073/pnas.1315006110
Citation  Zhu JG, et al. (2013) CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo. Proc Natl Acad Sci U S A 110(39):15650-5
abstractText  Bioactivation of vitamin D consists of two sequential hydroxylation steps to produce 1alpha,25-dihydroxyvitamin D3. It is clear that the second or 1alpha-hydroxylation step is carried out by a single enzyme, 25-hydroxyvitamin D 1alpha-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 1alpha,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 1alpha,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.
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