Figure 1.

Schematic of the synthesis of vitamin D (VitD) in the body. Cutaneous 7-dihydrocholesterol is converted into preVitD₃ following irradiation by ultraviolet light from the sun (2). Next, preVitD₃ forms cholecalciferol (VitD₃) by spontaneous isomerization. Subsequently, cholecalciferol is hydroxylated to 25-hydroxy-VitD (25(OH)D) or calcidiol, mainly in the liver, by the cytochrome P450 hydroxylase enzymes CYP27A1 and CYP2R1. Then, 25(OH)D is transported to the kidneys, where it is hydroxylated at the 1 alpha position by the 25-hydroxy-VitD-1 alpha hydroxylase (CYP27B1) to generate 1,25-dihydroxycholecalciferol [1,25 (OH)₂D] or calcitriol, which is the metabolically active compound (1, 2). Hydroxyvitamin D-24-hydroxylase (CYP24A1) is the enzyme responsible for the multi-step catabolism of both 25(OH)D and 1,25 (OH)₂D. The main product of 25(OH)D catabolism by CYP24A1 is 24,25-dihydroxycholecalciferol [24,25(OH)₂D], which is less active than calcitriol and presumably represents a metabolite destined for excretion. Importantly, VitD is not only converted from 25(OH)D to 1,25 (OH)₂D in the kidney but it is also activated locally by CYP27B1 in many tissues, including the brain, smooth muscle, breast, and prostate as well as cells of the immune system.