Comparison of cholesterol and its direct precursors along the biosynthetic pathway : effects of cholesterol, desmosterol and 7-dehydrocholesterol on saturated and unsaturated lipid bilayers

T. Róg, I. Vattulainen, Maurice Jansen, E. Ikonen, M.E.J. Karttunen

    Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

    44 Citaten (Scopus)

    Samenvatting

    Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellularmembranes has remained rather elusive. This is exemplified by the fact that the membrane properties of cholesterol are distinctly different from those of many other sterols. Here we elucidate this issue through atomic-scale simulations of desmosterol and 7-dehydrocholesterol (7DHC), which are immediate precursors of cholesterol in its two distinct biosynthetic pathways. While desmosterol and 7DHC differ from cholesterol only by one additional double bond, we find that their influence on saturated lipid bilayers is substantially different from cholesterol. The capability to form ordered regions in a saturated (dipalmitoyl-phosphatidylcholine) membrane is given by cholesterol>7DHC>desmosterol, indicating the important role of cholesterol in saturated lipid environments. For comparison, in an unsaturated (dioleoyl-phosphatidylcholine) bilayer, the membrane properties of all sterols were found to be essentially identical. Our studies indicate that the different membrane ordering properties of sterols can be characterized by a single experimentally accessible parameter, the sterol tilt. The smaller the tilt, the more ordered are the lipids around a given sterol. The molecular level mechanisms responsible for tilt modulation are found to be related to changes in local packing around the additional double bonds.
    Originele taal-2Engels
    Artikelnummer154508
    Aantal pagina's10
    TijdschriftJournal of Chemical Physics
    Volume129
    Nummer van het tijdschrift15
    DOI's
    StatusGepubliceerd - 2008

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