An Evaluation of the Biologic Activity and Vitamin D Receptor Binding Affinity of the Photoisomers of Vitamin D₃, Previtamin D₃ and Their Hydroxylated Derivatives

Abstract

During exposure to sunlight, the UVB portion of the solar spectrum (295-315 nm) photolyzes 7-dehydrocholesterol (7-DHC) in epidermis to previtamin D₃. Previtamin D₃ then thermoisomerizes to vitamin D₃ (1). Vitamin D₃ is hydroxylated in the liver at C-25 to form 25-hydroxyvitamin D₃ [25(OH)D₃], followed by hydroxylation at the C-lin kidneys to form 1,25dihydroxyvitamin D₃ [1,25(OH)₂D₃], the active form of vitamin D. However, further exposure to sunlight can photoisomerize previtamin D3 and vitamin D₃ to a variety of photoproducts, including 5,6-trans-vitamin D₃, tachysterol, and lumisterol (2,3). Since they are produced locally in the skin, their concentration could be very high. Among these photoproducts, tachysterol and 5,6-trans-vitamin D₃ have a pseudo-1-a-hydroxyl structure due to the 180 degree rotation of the 3-hydroxyl group during the isomerization (Figure 1).