Eight cytochrome P450s catalyze vitamin D metabolism

Vitamin D-3 plays a central role in calcium and phosphate homeostasis and is essential for the proper development and maintenance of bone. To exert its biological activities, vitamin D-3 has to receive enzymatic transformation to the active form, 1,25-dihydroxyvitamin D-3. The first step is the 25-hydroxylation reaction in the liver that produces 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. The 25-hydroxylation reaction is the prerequisite step for the subsequent 1alpha-hydroxylation and 24-hydroxylation reactions in the kidney. The 1alpha-hydroxylation reaction produces the active form of vitamin D-3, whereas 24-hydroxylation reaction leads to inactivation. Both reactions are strictly controlled by parathyroid hormone, 1,25-dihydroxyvitamin D-3, and calcium in a reciprocal manner in the kidney. At present, six cytochrome P450s (CYP2C11, 27A1, 2D25, 2R1, 3A4, and 2J3) are found to exhibit vitamin D 25-hydroxylation activities, and CYP27B1 and CYP24 are proved to be 1alpha-hydroxylase and 24-hydroxylase, respectively. The main focus of this review is to summarize the properties of individual P450 in light of their catalytic activities to understand their physiological significance.