Cited by 27Lipid Membrane Structure and BehaviorLipid metabolism and biosynthesisCaveolin-1 and cellular processes

Fast Diffusion of Very Long Chain Saturated Fatty Acids across a Bilayer Membrane and Their Rapid Extraction by Cyclodextrins

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Pillai, Biju K., Jasuja, Ravi, Simard, Jeffrey R., Hamilton, James A.·2009·Journal of Biological Chemistry

Abstract

Abnormalities in the transport of saturated very long chain fatty acids (VLCFA; >C18:0) contribute to their toxic levels in peroxisomal disorders of fatty acid metabolism, such as adrenoleukodystrophy and adrenomyeloneuropathy. We previously showed that VLCFA desorb much slower than normal dietary fatty acids from both albumin and protein-free lipid bilayers. The important step of transbilayer movement (flip-flop) was not measured directly as a consequence of this very slow desorption from donors, and the extremely low aqueous solubility of VLCFA precludes addition of unbound VLCFA to lipid membranes. We have overcome these limitations using methyl-beta-cyclodextrin to solubilize VLCFA for rapid delivery to "acceptor" phosphatidylcholine vesicles (small and large unilamellar) and to cells. VLCFA binding was monitored in real time with the fluorescent probe fluorescein-labeled phosphatidylethanolamine in the outer membrane leaflet, and entrapped pyranine was used to detect flip-flop across the membrane. The upper limit of the rate of flip-flop across the membrane was independent of temperature and media viscosity and was similar for model raft and non-raft membranes as well as living cells. We further showed that cyclodextrins can extract VLCFA rapidly (within seconds) from vesicles and cells, which have implications for the mechanism and potential alternative approaches to treat adrenoleukodystrophy. Because VLCFA diffuse through the lipid bilayer, proteins may not be required for their transport across the peroxisomal membrane.

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Crossref · 10.1074/jbc.m109.043737

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Authors
Pillai, B. K., Jasuja, R., Simard, J. R., & Hamilton, J. A.
Affiliations
Boston University (US)
Corresponding author
Hamilton, James A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-11
Volume
284
Issue
48
Pages
33296-33304
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2124886000
Cited by
27
References
63
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 2
FWCI
0.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (HL26335)
  • National Heart, Lung, and Blood Institute (2P01 HL-26335-21, P01HL026335)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
very long chain fatty acids, saturated fatty acids, methyl-β-cyclodextrin, fatty acid extraction, phosphatidylcholine vesicles, phosphatidylethanolamine, adrenoleukodystrophy, adrenomyeloneuropathy, peroxisomal disorders, fatty acid uptake, lipid rafts, fatty acid solubility
MeSH terms
Adrenoleukodystrophy, Biological Transport, Cell Line, Cell Membrane, Diffusion, Eicosanoic Acids, Fatty Acids, Fluorescent Dyes, Humans, Lipid Bilayers, Phosphatidylcholines, Spectrometry, Fluorescence, beta-Cyclodextrins

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