Kinetics and mechanism of free cholesterol exchange between human serum high- and low-density lipoproteins.
The mechanism of cholesterol and phosphatidylcholine (PC) exchange between human serum lipoproteins has been investigated by following the transfer of radiolabeled cholesterol and PC between high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Initially, [14C]cholesterol was present in the donor lipoprotein particle which was either HDL2, HDL3, or LDL. After incubation in saline solution for various times, the HDL and LDL were separated by precipitation of the LDL with Mn2+-heparin reagent. More than 90% of the [14C]cholesterol in donor HDL3 is transferred to LDL in a first-order process whose half-time is 2.9 min at 37 degrees C. This indicates that transfer of cholesterol molecules from the cholesterol ester/triglyceride core of HDL to the phospholipid/apoprotein monolayer at the surface of the particle is not rate limiting for exchange. The half-time for dipalmitoyl-PC exchange from HDL3 to LDL is 5 +/- h, indicating that the flux of PC is much lower than that of cholesterol. The half-times for [14C]cholesterol exchange from HDL2 and LDL at 37 degrees C are 4 and 45 min, respectively. The interfacial fluxes at 37 degrees C from the various lipoproteins are 4, 15, and 10 cholesterol molecules/(10 nm2 h), respectively, for LDL, HDL2, and HDL3. The rate of labeled cholesterol transfer from HDL3 is not affected when the concentration of LDL acceptor is increased 40-fold. The activation energies of cholesterol transfer between 4 and 37 degrees C for HDL3, HDL2, and LDL are 70 +/- 3, 75 +/- 3, and 78 +/- 3 KJ/mol, respectively. The general characteristics of the process of exchange of cholesterol between lipoproteins resemble those for exchange between small unilamellar vesicles. The results are only consistent with a mechanism of exchange in which cholesterol molecules diffuse through the aqueous phase; the experimental activation energy is associated with desorption of lipid from the donor lipoprotein into the aqueous phase.
D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008081:Liposomes; D010713:Phosphatidylcholines / Q000378:metabolism; D013816:Thermodynamics
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol