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

Tomasz Rog, Ilpo Vattulainen, Maurice Jansen, Elina Ikonen, Mikko Karttunen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

"Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes 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. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2996296]"
Original languageEnglish
JournalJournal of Chemical Physics
Volume2008
Issue number129
Pages (from-to)154508
Number of pages10
ISSN0021-9606
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 114 Physical sciences

Cite this

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title = "Comparison of cholesterol and its direct precursors along the biosynthetic pathway: effects of cholesterol, desmosterol and 7-dehydrocholesterol on saturated and unsaturated lipid bilayers",
abstract = "{"}Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes 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. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2996296]{"}",
keywords = "114 Physical sciences",
author = "Tomasz Rog and Ilpo Vattulainen and Maurice Jansen and Elina Ikonen and Mikko Karttunen",
year = "2008",
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journal = "Journal of Chemical Physics",
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TY - JOUR

T1 - Comparison of cholesterol and its direct precursors along the biosynthetic pathway

T2 - effects of cholesterol, desmosterol and 7-dehydrocholesterol on saturated and unsaturated lipid bilayers

AU - Rog, Tomasz

AU - Vattulainen, Ilpo

AU - Jansen, Maurice

AU - Ikonen, Elina

AU - Karttunen, Mikko

PY - 2008

Y1 - 2008

N2 - "Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes 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. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2996296]"

AB - "Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes 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. (C) 2008 American Institute of Physics. [DOI: 10.1063/1.2996296]"

KW - 114 Physical sciences

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DO - 10.1063/1.2996296

M3 - Article

VL - 2008

SP - 154508

JO - Journal of Chemical Physics

JF - Journal of Chemical Physics

SN - 0021-9606

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