Derived from cholesterol, vitamin D is biosynthesized from its prohormone cholecalciferol (D3), the product of solar ultraviolet irradiation of 7-dehydrocholesterol in the skin. In 1966, it was first recognized that vitamin D must undergo activation via two oxidative metabolic steps. The first oxidation to 25-hydroxycholecalciferol (25(OH)D3: calcifediol; Calderol) occurs in the endoplasmic reticulum of the liver and is catalyzed by vitamin D 25-hydroxylase. This activation step is not regulated by plasma calcium concentrations. The major circulating form (10-80 μg/mL) is 25(OH)D3, which also is the primary storage form of vitamin D.
