Vitamin D metabolism and effects in humans. Vitamin D3 is synthesized in skin from 7-dehydrocholesterol in a reaction catalyzed by solar UVB and can be delivered with food. In the circulation, it is bound by vitamin D binding protein (VDBP) and can reach liver, where is metabolized by cytochrome P450 family 2 subfamily R member 1 and family 27 subfamily A member 1 (CYP2R1 and CYP27A1) to 25-hydroxyvitamin D3 (25(OH)D), which is converted by CYP24A1 to 1,25-dihydroxyvitamin D3 (1,25(OH)2D, a blue tear) in a reaction that occurs mainly in kidney microtubule. 1,25(OH)2D is a biologically active metabolite of vitamin D that may interact with its transmembrane membrane-associated rapid response steroid-binding (MARRS) receptor and affect signaling, nuclear proteins and other transmembrane receptors, including growth factors (non-genomic action). 1,25(OH)2D may associate with its nuclear receptor Vitamin D receptor (VDR), which induces its heterodimerization with retinoid X receptor (RXR) and binding other proteins, including sequestosome 1 (p62/SQSTM1) and steroid receptor coactivator 1 (SRC1), to bind vitamin D response elements in the promoters of hundreds of genes to regulate their expression (genomic action).