Interaction of alpha-tocopherol with model human high-density lipoproteins.
The effects of alpha-tocopherol on the properties of model high-density lipoproteins (HDLs), composed of human apolipoprotein A-I and dimyristoylphosphatidylcholine, were investigated by physicochemical methods. The intrinsic fluorescence of alpha-tocopherol and its effects on the polarization of fluorescence of 1,6-diphenyl-1,3,5-hexatriene, which probes the hydrocarbon region of the lipids, and 4-heptadecyl-7-hydroxycoumarin, which is a probe of lipid surfaces, suggest that alpha-tocopherol is located at the lipid-water interface. Relative to cholesterol, alpha-tocopherol in lipid surfaces is virtually inert physicochemically. Incorporation of alpha-tocopherol into HDLs induces only a modest increase in particle size, no change in the transition temperature, and little change in lipid polarity and lipid-lipid interactions. Moreover, alpha-tocopherol has only a negligible effect on the kinetic parameters of the lipophilic enzyme lecithin:cholesterol acyltransferase, which binds to phosphatidylcholine surfaces and forms cholesteryl esters. However, alpha-tocopherol has a dramatic inhibitory effect on the rate of association of apolipoprotein A-I 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 dimyristoylphosphatidylcholine by inserting into defects within the lipid surface, thereby reducing the size and/or number of sites for insertion of apolipoprotein A-I.
Massey
J B
JB
Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77030 USA. jmassey@bcm.tmc.edu
Pownall
H J
HJ
D015081:2-Naphthylamine / Q000031:analogs & derivatives; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D055592:Biophysical Phenomena; D001703:Biophysics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002850:Chromatography, Gel; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D008956:Models, Chemical; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D016632:Apolipoprotein A-I; D005456:Fluorescent Dyes; D008075:Lipoproteins, HDL; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D014810:Vitamin E; C038517:prodan; D015081:2-Naphthylamine; D002785:Sterol O-Acyltransferase; D004134:Dimyristoylphosphatidylcholine