| Interactions of a very long chain fatty acid with model membranes and serum albumin. Implications for the pathogenesis of adrenoleukodystrophy. | |
| | |
MedLine Citation:
|
PMID: 7657817 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Adrenoleukodystrophy (ALD) is an inherited disorder of fatty acid metabolism marked by accumulation of very long chain saturated fatty acids (VLCFA), especially the 26-carbon acid, hexacosanoic acid (HA), in membranes and tissues. We have studied interactions of 13C-enriched HA with model membranes (phospholipid bilayer vesicles) and bovine serum albumin (BSA) by 13C NMR spectroscopy to compare properties of HA with those of typical dietary fatty acids. In phospholipid bilayers the carboxyl group of HA is localized in the aqueous interface, with an apparent pKa (7.4) similar to other fatty acids; the acyl chain must then penetrate very deeply into the membrane. Desorption of HA from vesicles (t1+2 = 3 h) is orders of magnitude slower than shorter chain fatty acids. In mixtures of vesicles and BSA, HA partitions much more favorably to phospholipid bilayers than typical fatty acids. BSA binds a maximum of only 1 mole of HA at one binding site. Calorimetric experiments show strong perturbations of acyl chains of phospholipids by HA. We predict that disruptive effects of VLCFA on cell membrane structure and function may explain the neurological manifestations of ALD patients. These effects will be further amplified by slow desorption of VLCFA from membranes and by the ineffective binding to serum albumin. |
| | |
Authors:
|
J K Ho; H Moser; Y Kishimoto; J A Hamilton |
Related Documents
:
|
14695647 - Free amino acids mimic the anabolic but not the proliferative effect of albumin in ok p... 1512247 - Photoaffinity labeling of fatty acid-binding proteins involved in long chain fatty acid... 8092987 - Purification and characterization of the human epidermal fatty acid-binding protein: lo... 14529287 - Fatty acid-binding proteins inhibit hydration of epoxyeicosatrienoic acids by soluble e... 17604037 - Identification of novel n-4 series polyunsaturated fatty acids in a deep-sea clam, caly... 23489367 - Hepatic triacylglycerol synthesis and secretion: dgat2 as the link between glycaemia an... |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: The Journal of clinical investigation Volume: 96 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1995 Sep |
Date Detail:
|
Created Date: 1995-10-04 Completed Date: 1995-10-04 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1455-63 Citation Subset: AIM; IM |
Affiliation:
|
Department of Biophysics-CABR 302, Boston University School of Medicine, Massachusetts 02118, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenoleukodystrophy
/
etiology* Animals Cattle Fatty Acids, Nonesterified / blood, chemistry* Fatty Acids, Unsaturated / blood, chemistry* Humans Lipid Bilayers* Magnetic Resonance Spectroscopy Models, Structural Models, Theoretical Serum Albumin, Bovine / chemistry*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
HL-26335/HL/NHLBI NIH HHS; NS13559/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids, Nonesterified; 0/Fatty Acids, Unsaturated; 0/Lipid Bilayers; 0/Serum Albumin, Bovine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Expression of human lecithin-cholesterol acyltransferase in transgenic mice. Effect of human apolipo...
Next Document: Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts.