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Cyp27b1 Vitamin D

Review

. 2014 Mar 20;21(3):319-29.

doi: 10.1016/j.chembiol.2013.12.016. Epub 2014 Feb 13.

Vitamin D metabolism, mechanism of action, and clinical applications

Affiliations

  • PMID: 24529992
  • PMCID: PMC3968073
  • DOI: 10.1016/j.chembiol.2013.12.016

Free PMC article

Review

Vitamin D metabolism, mechanism of action, and clinical applications

Daniel D Bikle . Chem Biol. .

Free PMC article

Abstract

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.

Figures

Figure 1
Figure 1. The Production and Metabolism of D2 and D3

D3 is produced in the skin from 7-DHC in a nonenzymatic process in which the B ring is broken by UVB radiation, and the pre-D3 formed isomerizes to D3 in a thermo-sensitive process. D3 is converted to 25OHD3 in the liver and elsewhere by a number of enzymes of which CYP2R1 is the most important. The regulation of this step is modest at best. The kidney and other tissues metabolize 25OHD to the active metabolite 1,25(OH)2D3 or the first step in the catabolic process 24,25(OH)2D3. The enzymes responsible, CYP27B1 and CYP24A1, respectively, are tightly controlled. Although the regulation differs in different tissues, in the kidney, CYP27B1 is stimulated by PTH and inhibited by FGF23 and high calcium (Ca) and phosphate (P). The regulation of CYP24A1 is just the opposite. 1,25(OH)2D3 also regulates its own production directly and by inhibiting PTH production, stimulating FGF23 production, and inducing CYP24A1.

Figure 2
Figure 2. Clinically Used Analogs of 1,25(OH)2

The structures of various vitamin D analogs currently in use clinically.

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Cyp27b1 Vitamin D

Source: https://pubmed.ncbi.nlm.nih.gov/24529992/

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