Bio- Chemical and Molecular Mechanisms of Vitamin D

biotechnology

1,25-Dihydroxyvitamin D3 (1,25D) is a vitamin D hormone metabolite that activates the vitamin D receptor to have biological effects (VDR). In the presence of 1,25D, the retinoid X receptor (RXR) and vitamin D receptor (VDR) create a heterodimer that binds to vitamin D responsive elements in the area of genes directly regulated by 1,25D. To promote the classic vitamin D activities including intestinal calcium and phosphate absorption and bone and calcium homeostasis, ligand-activated VDR-RXR recruits’ coactivator or corepressor complexes to control transcription of genes encoding the relevant protein genes. Thus, vitamin D action in a particular cell is dependent on the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. RANKL, SPP1 (osteopontin), and BGP control bone mineral remodeling; TRPV6, CaBP9k, and claudin 2 increase intestinal calcium absorption; TRPV5, klotho, and Npt2c regulate renal calcium and phosphate reabsorption. In keratinocytes, VDR seems to act without 1,25D ligand to regulate mammalian hair cycle by regulating genes such as CASP14, S100A8, SOSTDC1, and others that influence Wnt signaling. Other low-affinity non-vitamin D VDR ligands, such lithocholic acid, docosahexaenoic acid, and curcumin, have also been identified. Chronic diseases of aging including as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer may be slowed down by a combination of alternate VDR ligands and 1,25D/VDR gene expression regulation.

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