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Review
. 2010 Jun;39(2):243-53, table of contents.
doi: 10.1016/j.ecl.2010.02.002.

Vitamin D: metabolism

Sylvia Christakos  1 , Dare V Ajibade, Puneet Dhawan, Adam J Fechner, Leila J Mady
Affiliations
Review

Vitamin D: metabolism

Sylvia Christakos et al. Endocrinol Metab Clin North Am. 2010 Jun.

Abstract

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1alpha(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases.

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Figures

Figure 1
Figure 1
The metabolic pathway for vitamin D
Fig. 2
Fig. 2
Regulation of vitamin D hydroxylases by FGF23-Klotho. 1,25(OH)2D3 binds to VDR. The ligand-bound VDR forms a heterodimer with nuclear retinoid X receptor (RXR) resulting in increased the expression of FGF23 in osteocytes. Secreted FGF23 activates FGFR bound by klotho in renal tubular cells. FGF signaling suppresses expression of 1α(OH)ase and induces 24(OH)ase thereby inhibiting synthesis and promoting catabolism of 1,25(OH)2D3. Thus, the FGF23-Klotho results in decreased levels of 1,25(OH)2D3. Adapted from Kuro-o M (2008) Endocrine FGFs and Klothos: emerging concepts. Trends Endocrinol Metab 19:239–245
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Republished in

  • Vitamin D: metabolism.
    Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Christakos S, et al. Rheum Dis Clin North Am. 2012 Feb;38(1):1-11, vii. doi: 10.1016/j.rdc.2012.03.003. Rheum Dis Clin North Am. 2012. PMID: 22525839

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