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The many forms of vitamin D in the blood

Comment on the following paper at PandemicSurvivor Jan 2012
Which includes the following quote from an earlier paper

Only after the clinical outcomes related to the levels of the eight compounds,
  • 3-epi-25(OH)D3,
  • 25(OH)D3,
  • 3-epi-25(OH)D2,
  • 25(OH)D2,
  • 3-epi-25(OH)D3 sulfate,
  • 25(OH)D3sulfate,
  • 3-epi-25(OH)D2sulfate, and
  • 25(OH)D2sulfate
are determined will we be able to accurately assess the health benefits of vitamin D.

Note: these are in addition to D4, D5, and D6 and other “UV photoproducts”
CLICK HERE to search VitamiDWiki for photoproducts - 56 hits as of Jan 2012

Wonder what the vitamin D blood tests will actually test in the future.
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1?,25(OH)2-3-Epi-Vitamin D3, a Natural Physiological Metabolite of Vitamin D3: Its Synthesis, Biological Activity and Crystal Structure with Its Receptor

Ferdinand Molnár1,2, Rita Sigüeiro3, Yoshiteru Sato1, Clarisse Araujo3, Inge Schuster4, Pierre Antony1, Jean Peluso5, Christian Muller5, Antonio Mouriño3, Dino Moras1, Natacha Rochel1*
1 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, Illkirch, France,
2 School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland,
3 Departamento de Quimica Organica, Universidad de Santiago de Compostela and Unidad Asociada al CSIC, Santiago de Compostela, Spain,
4 Institute of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria,
5 Faculty of Pharmacy, Institut Gilbert Laustriat, UMR 7175 CNRS, University of Strasbourg, Illkirch, France

Background: The 1?,25-dihydroxy-3-epi-vitamin-D3 (1?,25(OH)2-3-epi-D3), a natural metabolite of the seco-steroid vitamin D3, exerts its biological activity through binding to its cognate vitamin D nuclear receptor (VDR), a ligand dependent transcription regulator. In vivo action of 1?,25(OH)2-3-epi-D3 is tissue-specific and exhibits lowest calcemic effect compared to that induced by 1?,25(OH)2D3. To further unveil the structural mechanism and structure-activity relationships of 1?,25(OH)2-3-epi-D3 and its receptor complex, we characterized some of its in vitro biological properties and solved its crystal structure complexed with human VDR ligand-binding domain (LBD).

Methodology/Principal Findings: In the present study, we report the more effective synthesis with fewer steps that provides higher yield of the 3-epimer of the 1?,25(OH)2D3. We solved the crystal structure of its complex with the human VDR-LBD and found that this natural metabolite displays specific adaptation of the ligand-binding pocket, as the 3-epimer maintains the number of hydrogen bonds by an alternative water-mediated interaction to compensate the abolished interaction with Ser278. In addition, the biological activity of the 1?,25(OH)2-3-epi-D3 in primary human keratinocytes and biochemical properties are comparable to 1?,25(OH)2D3.

Conclusions/Significance: The physiological role of this pathway as the specific biological action of the 3-epimer remains unclear. However, its high metabolic stability together with its significant biologic activity makes this natural metabolite an interesting ligand for clinical applications. Our new findings contribute to a better understanding at molecular level how natural metabolites of 1?,25(OH)2D3 lead to significant activity in biological systems and we conclude that the C3-epimerization pathway produces an active metabolite with similar biochemical and biological properties to those of the 1?,25(OH)2D3.

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The many forms of vitamin D in the blood        
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