For example, calcipotriol and 22-oxa calcitriol (OCT) are approved for the treatment of psoriasis paricalcitol, doxercalciferol, and falecalcitriol are approved for secondary hyperparathyroidism (nota bene: OCT and falecalcitriol are approved for use only in Japan).
For some circumstances, this has been achieved. These observations have spawned a major effort to develop vitamin D analogs that can separate the effects of the active metabolite 1,25-dihydroxyvitamin D (1,25(OH) 2D) on calcium and phosphate homeostasis from its effects on these other biologic processes and, in particular, to target just one such process. With the finding of the vitamin D receptor (VDR) in nearly every tissue and the more recent discovery of thousands of VDR binding sites throughout the genome controlling hundreds of genes, the interest in vitamin D and its impact on multiple biologic processes has accelerated tremendously as evidenced by the thousands of publications each year for the past several years. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application. Analogs of 1,25(OH) 2D are being developed to target specific diseases with minimal side effects. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. 1,25(OH) 2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs).
Both 25OHD and 1,25(OH) 2D are catabolized by CYP24A1. CYP2R1 is the most important 25-hydroxylase CYP27B1 is the key 1-hydroxylase.
Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH) 2D). Vitamin D 2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D 3 is made in the skin from 7-dehydrocholesterol under the influence of UV light.
0 kommentar(er)
