| Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. | |
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MedLine Citation:
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PMID: 10471774 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling. |
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Authors:
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P Schönfeld; H Struy |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: FEBS letters Volume: 457 ISSN: 0014-5793 ISO Abbreviation: FEBS Lett. Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-10-14 Completed Date: 1999-10-14 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0155157 Medline TA: FEBS Lett Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 179-83 Citation Subset: IM |
Affiliation:
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Institute of Biochemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany. pschoen@medizin.uni-magdeburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Markers Biological Transport Electron Spin Resonance Spectroscopy Humans Intracellular Membranes / drug effects, metabolism Membrane Proteins / chemistry, drug effects* Mitochondria, Liver / drug effects*, metabolism Phospholipids / metabolism Phytanic Acid / pharmacology* Protein Conformation / drug effects Refsum Disease / diagnosis, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Membrane Proteins; 0/Phospholipids; 14721-66-5/Phytanic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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