Document Detail


Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease.
MedLine Citation:
PMID:  11724659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alter membrane composition and structure, thereby affecting membrane function(s). The anti-metabolite hypothesis suggests that an accumulation of phytanic acid in membranes may interfere with vitamin E function. These two hypotheses were investigated by studying the effects of modulating phytanic acid and alpha-tocopherol concentrations on the fatty acid composition and certain physical parameters of cultured retinal cells. Results showed that (a) the phospholipid fraction of retinal cells readily incorporated phytanic acid, (b) the incorporation of phytanic acid increased membrane fluidity, (c) there was no competition for uptake between phytanic acid and alpha-tocopherol, and (d) the incorporation of phytanic acid did not increase the susceptibility of membranes to lipid peroxidation in vitro. These results obtained with cultured retinal cells suggest that the molecular distortion hypothesis, but not the anti-metabolite hypothesis, could explain the pathogenesis of adult Refsum disease. In vitro tissue culture models can, however, only approximate to the much more complex situation that occurs in vivo.
Authors:
S P Young; A W Johnson; D P Muller
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  101     ISSN:  0143-5221     ISO Abbreviation:  Clin. Sci.     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2001-11-28     Completed Date:  2002-01-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  697-705     Citation Subset:  IM    
Affiliation:
Biochemistry, Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cell Line
Cell Membrane / drug effects
Culture Techniques
Dose-Response Relationship, Drug
Humans
Lipid Peroxidation / drug effects
Membrane Fluidity / drug effects
Membrane Lipids / metabolism*
Models, Biological
Phospholipids / metabolism
Phytanic Acid / pharmacology*
Rats
Refsum Disease / metabolism*
Retina / cytology,  drug effects*,  metabolism
Retinal Neoplasms / metabolism
Retinoblastoma / metabolism
Tumor Cells, Cultured
alpha-Tocopherol / pharmacology*
Chemical
Reg. No./Substance:
0/Membrane Lipids; 0/Phospholipids; 14721-66-5/Phytanic Acid; 59-02-9/alpha-Tocopherol

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


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