Fast Diffusion of Very Long Chain Saturated Fatty Acids across a Bilayer Membrane and Their Rapid Extraction by Cyclodextrins
Open accessAbstract
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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C26:0 has similar hydrophobicity and dissociation rate from membranes as cholesterol.
“the VLCFA C26:0 has similar hydrophobicity and dissociation rate from membranes as cholesterol51,52”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [52]
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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)
- PMC
- PMC2785172
- 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
- hybrid
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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