Incorporation of cholesterol into apolipoprotein A-I-dimyristoylphosphatidylcholine recombinants.
Apolipoprotein A-I (apoA-I) spontaneously associates with dimyristoylphosphatidylcholine (DMPC) liposomes to form discoidal high-density lipoprotein (HDL) recombinants. The uptake of cholesterol by this model HDL was studied by incubation with Celite-dispersed cholesterol. Separation of the resulting complexes by gradient centrifugation and gel filtration showed a heterogeneous distribution of particle size and composition as a consequence of the disruption and rearrangement of the recombinants. Quantitation of the amount of cholesterol taken up gave values between about 28 and 40 mol% cholesterol for the fractions within the protein peaks; the fractions with the lowest DMPC/apoA-I ratios had the lowest cholesterol contents. In another set of experiments, the association of apoA-I with DMPC-cholesterol liposomes was shown to result in complexes with characteristics similar to those obtained by the cholesterol-uptake experiments. Low concentrations of cholesterol in the liposomes enhanced the rate of lipid-protein association, but larger amounts decreased the yield of complexes by making the process thermodynamically and kinetically unfavorable. The enthalpy of recombinant formation increased with decreasing lipid/protein ratio and increasing cholesterol content, and became endothermic at about 23 mol% cholesterol. The effect of cholesterol on the thermal properties of HDL recombinants suggests that cholesterol is partially excluded from the boundary region adjacent to apoA-I. It is concluded that discoidal HDL recombinants, as a model for 'nascent' HDL, can acquire substantial amounts of cholesterol, which may be of great physiological importance for the reverse cholesterol transport and prevention of atherosclerosis.
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001665:Binding Sites; D002151:Calorimetry; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine; D004347:Drug Interactions; D006801:Humans; D008081:Liposomes; D046911:Macromolecular Substances; D008956:Models, Chemical
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D008081:Liposomes; D046911:Macromolecular Substances; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine