Figure 1.

Calcitriol activation pathways and biological functions in target tissues. In human, vitamin D₃ is the predominant form of vitamin D, which is synthesized from 7- dehydrocholesterol upon sunlight exposure. Vitamin D may also be obtained from dietary sources or supplements as either vitamin D₂ or D₃. Vitamin D₃ binds to vitamin D-binding protein (DBP) in the bloodstream and then taken up within hours following synthesis or dietary uptake to be activated by liver and kidney. In the liver it is first converted by mitochondrial cytochrome P450 (CYP) enzyme CYP27A1, microsomal CYP2J3 and CYP2R1 to 25-hydroxyvitamin D. This molecule is further converted by the renal enzyme 1-a hydroxylase (CYP27B1) to 1,25 dihydroxycholecalciferol (calcitriol), which is the active form of vitamin D. Finally, calcitriol binds to intracellular vitamin D receptor (VDR) in most cells in the body by functioning both as a paracrine and an autocrine agent.