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

Although the vitamin D endocrine system has been well defined and the enzyme responsible for converting 25-hydroxyvitamin D to the final hormone, 1α,25-dihydroxyvitamin D₃, is well understood, the enzyme responsible for the conversion of vitamin D to the blood form, 25-hydroxyvitamin D, has not been clearly identified. A case has been made for vitamin D 25-hydroxylase CYP2R1 as the responsible enzyme, but proof is lacking. We have produced a null mutant mouse lacking CYP2R1. With this model, we have shown that CYP2R1 is the major but not exclusive 25-hydroxylase and that there remains another significant enzyme responsible for this step in vitamin D activation that has yet to be identified.