Simplified version of vitamin D metabolism. Vitamin D, produced mainly from ultraviolet B (UVB) action on the skin, but also available from the diet, binds vitamin D binding protein (DBP) and is transported to the liver where different mitochondrial cytochrome P450 enzymes (CYP) hydroxylate it to form 25(OH)D. This is transported by DBP predominantly to the kidneys, where CYP enzymes hydroxylate it to the active form, 1,25(OH)₂D₃. However, immune cells also have the CYP enzymes required to activate 1,25(OH)₂D₃. Being lipophilic, 1,25(OH)₂D₃ is able to traverse the cell membrane and act within the cell by binding to vitamin D receptors (VDR) in the nucleus. VDR are ligand-activated transcription factors that interact with vitamin D response elements (VDRE) on vitamin D-regulated genes either as homodimers or heterodimers with the retinoid X receptors (RXR). Vitamin D is also regulated by CYP enzymes which inactivate calcitriol into water-soluble derivatives. Vitamin D binding to the VDR enhances CYP24A1 and down-regulates CYP27B1, which is an important negative feedback mechanism regulating vitamin D levels. For more detail refer to [7].