The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health

Figure 1

Synthesis of vitamin D precursors and metabolites. Photosynthesis in the skin, dietary intake, and supplements are the sources of vitamin D. Melanin and sunblock preparations, which protect the skin from sunlight damage, reduce the UVB penetration resulting in decreased cutaneous photoconversion of 7-dehydrocholesterol to vitamin D [6]. Older persons have a decreased capacity to produce cutaneous previtamin D₃ [2]. CYP2R1 is the major enzyme responsible for hydroxylation of vitamin D in the liver into 25(OH)D. 25(OH)D is then hydroxylated by the enzyme CYP27B1 in the kidney to become hormonal 1,25(OH)₂D. CYP27B1 is also expressed by nonrenal tissues [1, 4–6]. 1,25(OH)₂D, the biologically active form of vitamin D, acts on target cells including cells of the parathyroid glands, osteoblasts, dendritic cells, T cells, and keratinocytes. Small amounts of 1,25(OH)₂D can also be produced locally in the skin by cutaneous keratinocytes, but only insignificantly contributing to the blood levels of 1,25(OH)₂D. Usually 25(OH)D and 1,25(OH)₂D are metabolized by CYP24A1 into water soluble inactive forms which are secreted in bile [7, 8].