Interaction of ApoA-1 and ApoE-3 with triglyceride-phospholipid emulsions containing increasing cholesterol concentrations. Model of triglyceride-rich nascent and remnant lipoproteins.
The cholesterol content of triglyceride-rich lipoproteins increases during their catabolism in circulation. We therefore studied the binding of the exchangeable apoprotein apoA-1 and apoE-3 to triolein-rich emulsions with increasing cholesterol content. Five emulsion systems containing 83.1-88.8% (w/w) triolein, 9.3-10.1% egg yolk phosphatidylcholine, and 1.1-7.3% cholesterol were isolated from sonicated lipid mixtures by flotation. Negative stain EM of emulsions containing 1.1 and 7.3% cholesterol showed polydisperse populations of large spherical particles with diameters of 106 +/- 39 and 108 +/- 57 nm. These values are similar to particle diameters calculated from the lipid composition data. No lamellar structures were observed by EM, even after addition of apoA-1 at a molar ratio to lecithin of 10(-2). Apolipoproteins apoA-1 and apoE-3 bound to the particles in a saturable manner without altering particle morphology. We found a dissociation constant Kd = 7.4 x 10(-7) M and a binding capacity N = 3.9 x 10(-3) proteins/lecithin for apoA-1 with particles containing 1.1% cholesterol; the Kd and N values for apoE-3 were very similar. When the emulsion particles were saturated with cholesterol at 7.3%, the protein binding capacity N sharply decreased to 0.6 x 10(-3) (apoA-1) and 0.7 x 10(-3) proteins/lecithin (apoE-3), but the Kd values were virtually unchanged. No change in N occurred when the particle cholesterol content was increased from 1.1 to 3.7%, which spans the normal physiological range. These results suggest that increases in lipoprotein cholesterol content above 3.7% may be responsible for impaired apoprotein redistribution and altered metabolism of remnants such as beta-VLDL.
Derksen
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Department of Medicine, Boston University School of Medicine, Housman Medical Research Center, Massachusetts 02118.
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D016632:Apolipoprotein A-I; D053318:Apolipoprotein E3; D001054:Apolipoproteins A / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D004655:Emulsions; D006801:Humans; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000378:metabolism*; D013499:Surface Properties; D014304:Triolein / Q000378:metabolism*; D014465:Ultrasonics
D016632:Apolipoprotein A-I; D053318:Apolipoprotein E3; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D004655:Emulsions; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D014304:Triolein