Vitamin D Metabolism, Mechanism of Action, and Clinical Applications

Vitamin D Metabolism, Mechanism of Action, and Clinical Applications

2014 March 20; 21(3): 319–329. | Daniel D. Bikle
The article provides a comprehensive overview of vitamin D metabolism, mechanism of action, and clinical applications. Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol under UV light, while vitamin D2 is derived from ergosterol in plants and fungi. The metabolism of vitamin D involves three main steps: 25-hydroxylation by CYP2R1, 1α-hydroxylation by CYP27B1, and 24-hydroxylation by CYP24A1. These enzymes are crucial for the activation and regulation of vitamin D. The active form, 1,25-dihydroxyvitamin D (1,25(OH)2D), binds to the vitamin D receptor (VDR) to regulate gene expression through genomic and nongenomic actions. The VDR forms a complex with retinoid X receptor (RXR) to bind to vitamin D response elements (VDREs) in the genome, influencing hundreds of genes. Vitamin D analogs, such as calcipotriol and 22-oxa calcitriol, have been developed to target specific diseases with minimal side effects. Clinical applications of vitamin D include the prevention and treatment of rickets, osteoporosis, psoriasis, hyperparathyroidism, and the potential benefits in cancer, cardiovascular disease, and immune function. However, more randomized clinical trials are needed to confirm the efficacy of these treatments.The article provides a comprehensive overview of vitamin D metabolism, mechanism of action, and clinical applications. Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol under UV light, while vitamin D2 is derived from ergosterol in plants and fungi. The metabolism of vitamin D involves three main steps: 25-hydroxylation by CYP2R1, 1α-hydroxylation by CYP27B1, and 24-hydroxylation by CYP24A1. These enzymes are crucial for the activation and regulation of vitamin D. The active form, 1,25-dihydroxyvitamin D (1,25(OH)2D), binds to the vitamin D receptor (VDR) to regulate gene expression through genomic and nongenomic actions. The VDR forms a complex with retinoid X receptor (RXR) to bind to vitamin D response elements (VDREs) in the genome, influencing hundreds of genes. Vitamin D analogs, such as calcipotriol and 22-oxa calcitriol, have been developed to target specific diseases with minimal side effects. Clinical applications of vitamin D include the prevention and treatment of rickets, osteoporosis, psoriasis, hyperparathyroidism, and the potential benefits in cancer, cardiovascular disease, and immune function. However, more randomized clinical trials are needed to confirm the efficacy of these treatments.
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[slides and audio] Vitamin D metabolism%2C mechanism of action%2C and clinical applications.