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. |