Plasma protein-facilitated coupled exchange of phosphatidylcholine and cholesteryl ester in the absence of cholesterol esterification.

A protein(s) which catalyzes the exchange of phosphatidylcholine and cholesteryl ester between plasma lipoproteins has been purified 10,000-fold from lipoprotein-free human plasma. The apparent molecular weight of the protein of the active fraction, designated lipid transfer complex (LTC), is approximately 61,000; when electrophoresed in 6 M urea, 0.1% sodium dodecyl sulfate on a 3-20% polyacrylamide gradient, the protein appears as a doublet of molecular weights 58,000 and 63,000. The active material is a glycoprotein which binds to concanavalin A. Human LTC is a lipid-protein complex with phospholipid, cholesterol, cholesteryl ester, and glyceride comprising 7% of the total mass. A similar glycoprotein (or glycoproteins) exists in rat plasma, although the fold-purification thus far achieved is low: about 500-fold. Moreover, the rat preparation enhances exchange of phosphatidylcholine, but does not appreciably enhance exchange of cholesteryl ester. Partially purified LTC (less than or equal to 3500-fold) exists in a complex with lecithin: cholesterol acyltransferase. Active lecithin: cholesterol acyltransferase is not, however, required for exchange of phosphatidylcholine or cholesteryl ester facilitated by human LTC. The rates of exchange of phosphatidylcholine and cholesteryl ester facilitated by human LTC are equal. Coupled lipid exchange occurs at all stages of LTC purification, at values of pH between 5 and 10, and at ionic strengths as great as 0.9. Moreover, phosphatidylcholine and cholesteryl ester are exchanged with 1:1 stoichiometry in the presence of thiol group reagents such as 5,5'-dithiobis-(2-nitrobenzoic acid). Both lipid exchange activities are relatively resistant to elevated temperatures. Coupled exchange of phospholipid and neutral lipid is not dictated by the nature of the lipoprotein donor and acceptor substrates: bovine liver phospholipid exchange protein catalyzes exchange of phosphatidylcholine but not cholesteryl ester between low and high density lipoproteins under conditions identical with those in which human LTC facilitates exchange of both lipids.