Molecular Recognition and Structure-Activity Relations in Vitamin D-Binding Protein and Vitamin D Receptor

Abstract

1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], a dihydroxylated metabolite of vitamin D3, is a secosteroid with diverse biological actions (1,2). Vitamin D3 is synthesized in skin by the interaction of ultraviolet (UV) light from the sun with 7-dehydrocholesterol, a constituent of the epidermis. The product of this photolytic reaction is predominantly a ring-opened compound called previtamin D3, which then isomerizes slowly by the body temperature to vitamin D3. After the cutaneous synthesis, vitamin D3 diffuses into the blood stream and is sequentially oxidized by specific P450-containing hydroxylases in the liver to form 25-hydroxyvitamin D3 [25(OH)D3], and in the kidney to form lα,25(OH)2 D3, the active form of vitamin D hormone. After the biosynthesis, lα,25(OH)2 D3 trans-locates into numerous target organs like intestine, bone, skin, pituitary, kidney, ovary, etc., where its various biologic functions manifest (see below) (Fig. 1). In addition to vitamin D3 (synthesized in the skin), another chemical form of vitamin D3 (called vitamin D2, which is obtained primarily from diet and vitamin D supplements) and all of its metabolites exist in nature. Vitamin D2 is metabolized to 25-hydroxyvitamin D2 and 1α,25-dihydroxyvitamin D2, similar to vitamin D3 (1).