Interaction of alpha-tocopherol with model human high-density lipoproteins

Citation
Jb. Massey et Hj. Pownall, Interaction of alpha-tocopherol with model human high-density lipoproteins, BIOPHYS J, 75(6), 1998, pp. 2923-2931
Citations number
50
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOPHYSICAL JOURNAL
ISSN journal
00063495 → ACNP
Volume
75
Issue
6
Year of publication
1998
Pages
2923 - 2931
Database
ISI
SICI code
0006-3495(199812)75:6<2923:IOAWMH>2.0.ZU;2-3
Abstract
The effects of alpha-tocopherol on the properties of model high-density lip oproteins (HDLs), composed of human apolipoprotein A-l and dimyristoylphosp hatidylcholine, were investigated by physicochemical methods. The intrinsic fluorescence of alpha-tocopherol and its effects on the polarization of fl uorescence of 1,6-diphenyl-1,3,5-hexatriene, which probes the hydrocarbon r egion of the lipids, and 4-heptadecyl-7-hydroxycoumarin, which is a probe o f lipid surfaces, suggest that alpha-tocopherol is located at the lipid-wat er interface. Relative to cholesterol, alpha-tocopherol in lipid surfaces i s virtually inert physicochemically. Incorporation of alpha-tocopherol into HDLs induces only a modest increase in particle size, no change in the tra nsition temperature, and little change in lipid polarity and lipid-lipid in teractions. Moreover, alpha-tocopherol has only a negligible effect on the kinetic parameters of the lipophilic enzyme lecithin:cholesterol acyltransf erase, which binds to phosphatidylcholine surfaces and forms cholesteryl es ters. However, alpha-tocopherol has a dramatic inhibitory effect on the rat e of association of apolipoprotein A-l with dimyristoylphosphatidylcholine, a process that occurs through the insertion of the protein into preformed defects in the lipid surface. It is proposed that alpha-tocopherol inhibits the rate of association of apolipoprotein A-I with dimyristoylphosphatidyl choline by inserting into defects within the lipid surface, thereby reducin g the size and/or number of sites for insertion of apolipoprotein A-l.