Document Detail

Nonesterified fatty acids induce transmembrane monovalent cation flux: host-guest interactions as determinants of fatty acid-induced ion transport.
MedLine Citation:
PMID:  9649333     Owner:  NLM     Status:  MEDLINE    
Nonesterified fatty acids are key intermediates in cellular metabolism whose intracellular concentration is regulated by multiple anabolic, catabolic, and oxidative enzymatic cascades. Herein, we demonstrate that fatty acids induce transmembrane monovalent cation flux with an apparent rate constant kapp = 10(-)4 - 10(-)3 s-1. Fatty acid-induced cation efflux exploits the ionic association of the cation with the carboxylate anion of the fatty acid and the subsequent transmembrane flip-flop of the fatty acid-cation complex. Rates of fatty acid-induced transmembrane cation flux were dependent upon complex host-guest interactions between the fatty acid-cation complex and the phospholipid constituents which comprise the membrane bilayer including (1) the degree of unsaturation of the fatty acid guest and the regiospecificity and stereospecificity of its olefinic linkages; (2) the phospholipid subclass and individual molecular species which constitute the host membrane phospholipids; (3) impedance matching of host and guest hydrophobic characteristics; and (4) the cholesterol content of the membrane bilayer. Arrhenius analysis demonstrated that fatty acid-induced K+ efflux was facilitated largely by changes in the entropy of activation of ion translocation and not the energy of activation. Moreover, Arrhenius analysis demonstrated that the energy of activation of ion translocation was phospholipid subclass specific. For example, arachidonic acid-induced cation efflux in membranes comprised of 16:0-18:1 plasmenylcholine possessed an Ea = 5.3 +/- 0.4 kcal/mol, while that for 16:0-18:1 phosphatidylcholine was 7.2 +/- 0.5 kcal/mol. Electrophysiologic measurements of planar lipid membranes containing 10 mol % arachidonic acid as a substitutional impurity confirmed the ability of physiologically relevant amounts of fatty acid to induce ion translocation with a specific conductance of 2.6 +/- 0.3 microS/cm2. Collectively, these results demonstrate that fatty acids facilitate transmembrane cation flux by an ion carrier type mechanism and suggest that fatty acid-mediated ion transport contributes to the leakage current present in many cell types and thus potentially modulates cellular responsivity during signal transduction where the intracellular content of fatty acids changes dramatically.
Y Zeng; X Han; P Schlesinger; R W Gross
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  37     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-07-23     Completed Date:  1998-07-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9497-508     Citation Subset:  IM    
Division of Bioorganic Chemistry, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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MeSH Terms
Arachidonic Acid / metabolism
Biological Transport / drug effects
Cell Membrane Permeability / drug effects*
Chlorides / metabolism
Cholesterol / pharmacology
Fatty Acids, Nonesterified / pharmacology*
Lipid Bilayers / metabolism
Liposomes / metabolism
Membrane Potentials / drug effects
Models, Chemical
Patch-Clamp Techniques
Phosphatidylcholines / metabolism
Plasmalogens / metabolism
Potassium / metabolism*
Sodium / metabolism
Structure-Activity Relationship
Grant Support
1 PO1 HL 57278-02/HL/NHLBI NIH HHS; 2 R01 HL 41250-06A1/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Chlorides; 0/Fatty Acids, Nonesterified; 0/Lipid Bilayers; 0/Liposomes; 0/Phosphatidylcholines; 0/Plasmalogens; 0/choline plasmalogens; 506-32-1/Arachidonic Acid; 57-88-5/Cholesterol; 7440-09-7/Potassium; 7440-23-5/Sodium

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