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

JG Zhu, JT Ochalek, M Kaufmann… - Proceedings of the …, 2013 - National Acad Sciences
JG Zhu, JT Ochalek, M Kaufmann, G Jones, HF DeLuca
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences