Bikle Daniel D
VA Medical Center, Department of Medicine and Dermatology, University of California, San Francisco, San Francisco, CA 94121, USA.
Chem Biol. 2014 Mar 20;21(3):319-29. doi: 10.1016/j.chembiol.2013.12.016. Epub 2014 Feb 13.
Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 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). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.
维生素D3是皮肤中的7-脱氢胆固醇在紫外线的作用下合成的。维生素D2（麦角钙化醇）来源于植物甾醇麦角固醇。维生素D首先代谢为25-羟基维生素D（25OHD），然后代谢为激素形式的1,25-二羟基维生素D（1,25(OH)2D）。CYP2R1是最重要的25-羟化酶；CYP27B1是关键的1-羟化酶。25OHD和1,25(OH)2D都由CYP24A1分解代谢。1,25(OH)2D是维生素D受体（VDR）的配体，VDR是一种转录因子，可与DNA中称为维生素D反应元件（VDREs）的位点结合。这些结合位点有成千上万个，以细胞特异性方式调节数百个基因。VDR调节的转录依赖于共调节因子，其分布也是细胞特异性的。正在开发1,25(OH)2D的类似物，以靶向特定疾病并使副作用最小化。本综述将探讨维生素D代谢、作用机制和临床应用的这些不同方面。
