Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Abstract

, [1,25(OH) 2 D 3 ] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH) 2 D 3 action involves the direct binding of the 1,25(OH) 2 D 3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH) 2 D 3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH) 2 D 3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

Cancer in North Cyprus: 1. Current Status, An Overview

“…Net effects include strong suppression of cancer cell proliferation and differentiation (30). More recent evidence suggests, however, that vitamin D can also exert fast, non-genomic actions (31,32). …”

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“…[3][4][5] Vitamin D 3 , when converted in the kidney to calcitriol, acts as a potent steroid hormone on various organs, such as the intestine, bone, kidney, and parathyroid, primarily to promote homeostasis of blood calcium levels. 6,7 As a result of adverse events related to the deleterious effects of hypercalcemia, calcitriol analogs, such as paricalcitol, have been developed to circumvent this problem. 8,9 A number of clinical trials have demonstrated the efficacy of paricalcitol in decreasing proteinuria [10][11][12] and excessive parathyroid hormone (PTH) due to secondary hyperparathyroidism (SHPT) associated with chronic kidney disease [13][14][15] or following kidney transplant.…”

The relationship between ultraviolet, vitamin d and blood glucose, in vivo study

“…The mechanism of vitamin D is photosynthesized in the skin by the action of solar UVB radiation was 7-dehydrocholesterol convert to Vitamin D3 [7]. The humans need continuous glucose level in their blood, which allows the brain to work even with minimum function.…”