Vitamin D (calciferol) metabolism

Vitamin D3 (VD3, cholecalciferol) is a steroid hormone that principally plays roles in regulating intestinal calcium absorption and in bone metabolism. It is obtained from the diet and produced in the skin by photolysis of 7-dehydrocholesterol and released into the bloodstream. Very few foods (eg. oily fish, mushrooms exposed to sunlight and cod liver oil) are natural sources of vitamin D. A small number of countries in the world artificially fortify a few foods with vitamin D. The metabolites of vitamin D are carried in the circulation bound to a plasma protein called vitamin D binding protein (GC) (for review see Delanghe et al. 2015, Chun 2012). Vitamin D undergoes two subsequent hydroxylations to form the active form of the vitamin, 1-alpha, 25-dihydroxyvitamin D (1,25(OH)2D). The first hydroxylation takes place in the liver followed by subsequent transport to the kidney where the second hydroxylation takes place. 1,25(OH)2D acts by binding to nuclear vitamin D receptors and it has been estimated that upwards of 2000 genes are directly or indirectly regulated which are involved in calcium homeostasis, immune responses, cellular growth, differentiation and apoptosis. Inactivation of 1,25(OH)2D occurs via C23/C24 oxidation catalysed by cytochrome CYP24A1 enzyme.

Summary from Reactome (R-HSA-196791), read 2026-09-23.