Figure 1.

Vitamin D biosynthesis and action. Precursors of vitamin D are incorporated by foods, supplements, or synthesized by skin after UV-radiation and heat. These precursors are stocked in adipose tissue or carried to liver and kidneys for hydroxylation by the enzymes P450C25 and P450C1 hydroxylases, respectively. The metabolic active form of vitamin D (1,25(OH)₂D₃) is transported through the bloodstream by vitamin-D-binding protein (DBP). In target cells, 1,25(OH)₂D₃ follows two distinct pathways. Target cells that have nuclear vitamin D receptors (nVDR) will trigger a better understood pathway involving: activation of nVDR by 1,25(OH)₂D₃; connection with other transcription factors, such as retinoid X receptors (RXR); formation of a complex capable of recognizing response elements of vitamin D (VDRE); and induction or repression of specific genes. On the other hand, target cells that have membrane vitamin D receptors (mVDR) will trigger a less understood pathway, maybe involving the activation of mVDR by 1,25(OH)₂D₃ and the rapid opening of a G-protein-coupled membrane-bound calcium channel. These mechanisms modulate the synthesis of parathormone (PTH) and, together with the diminished PTH levels, act in the metabolism of skeletal and non-skeletal tissues. Adapted with permission from Nature Publishing Group: Nature Reviews Cancer [18] copyright 2003.