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Desmosterol May Replace Cholesterol in Lipid Membranes

Daniel Huster ^* , Holger A. Scheidt ^*, Klaus Arnold , Andreas Herrmann  and Peter Müller 

^* Junior Research Group "Solid-State NMR Studies of Membrane-Associated Proteins", Biotechnological-Biomedical Center, University of Leipzig, Germany; Institute of Medical Physics and Biophysics, University of Leipzig, Germany; and Humboldt-University Berlin, Institute of Biology/Biophysics, Berlin, Germany

Correspondence: Address reprint requests to Peter Müller, Tel.: 49-30-2093-8830; Fax: 49-30-2093-8585; E-mail: peter.mueller.3{at}rz.hu-berlin.de.

Recently, knockout mice entirely lacking cholesterol have been described as showing only a mild phenotype. For these animals, synthesis of cholesterol was interrupted at the level of its immediate precursor, desmosterol. Since cholesterol is a major and essential constituent of mammalian cellular membranes, we asked whether cholesterol with its specific impact on membrane properties might be replaced by desmosterol. By employing various approaches of NMR, fluorescence, and EPR spectroscopy, we found that the properties of phospholipid membranes like lipid packing in the presence of cholesterol or desmosterol are very similar. However, for lanosterol, a more distant precursor of cholesterol synthesis, we found significant differences in comparison with cholesterol and desmosterol. Our results show that, from the point of view of membrane biophysics, cholesterol and desmosterol behave identically and, therefore, replacement of cholesterol by desmosterol may not impact organism homeostasis.

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