Document Detail


Perturbations of membrane structure by cholesterol and cholesterol derivatives are determined by sterol orientation.
MedLine Citation:
PMID:  19334779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholesterol is essential for proper function and regulation of eukaryotic membranes, and significant amounts of metabolic energy are dedicated to controlling cellular cholesterol levels. Oxidation products of cholesterol, the oxysterols, are enzymatically produced molecules that play a major role in mediating cholesterol homeostasis through mechanisms which have not yet been fully elucidated. Certain oxysterols are known to have direct effects on membrane permeability and structure, effects that are strikingly different from that of cholesterol. We use molecular dynamics simulations of these oxysterols in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers to explain the structural origins for the differing effects of cholesterol and 25-hydroxycholesterol on bilayer properties. In particular, we demonstrate that the source for these differing perturbations is the much wider range of molecular orientations accessible to 25-hydroxycholesterol when compared to cholesterol. This study shows that direct membrane perturbation by side-chain oxysterols is significant and suggests that these membrane perturbations may play a role in the oxysterol regulation of cholesterol homeostasis.
Authors:
Brett N Olsen; Paul H Schlesinger; Nathan A Baker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  131     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-06-29     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4854-65     Citation Subset:  IM    
Affiliation:
Molecular Cell Biology Graduate Program, Center for Computational Biology, Washington University in St. Louis, 700 South Euclid Avenue, Campus Box 8036, St. Louis, Missouri 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Cholesterol / analogs & derivatives*,  chemistry*,  metabolism
Compressive Strength
Computer Simulation
Elasticity
Hydrogen Bonding
Hydroxycholesterols / chemistry,  metabolism
Lipid Bilayers / chemistry*,  metabolism
Models, Biological
Models, Molecular
Molecular Structure
Oxidation-Reduction
Phosphatidylcholines / chemistry*,  metabolism
Grant Support
ID/Acronym/Agency:
T32 GM007067/GM/NIGMS NIH HHS; T32 GM007067/GM/NIGMS NIH HHS; T32 GM007067-34/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxycholesterols; 0/Lipid Bilayers; 0/Phosphatidylcholines; 57-88-5/Cholesterol; 767JTD2N31/25-hydroxycholesterol; TE895536Y5/1-palmitoyl-2-oleoylphosphatidylcholine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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