Interaction of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in the transport of cholesteryl ester into sphingomyelin liposomes.

When isolated lecithin:cholesterol acyltransferase was incubated with cholesterol-lecithin liposomes in the presence of apolipoprotein A-1, cholesteryl ester accumulated until a maximal ester/lecithin weight ratio of 0.03 was reached. This was independent of the amount of enzyme present or the proportion of cholesterol relative to lecithin. The inhibition of transferase associated with accumulation of cholesteryl ester was relieved by additional lecithin-cholesterol liposomes but not by addition of sphingomyelin liposomes containing the same proportion of substrate unesterified cholesterol. These results indicate that it is the accumulation of cholesteryl ester product which directly inhibits transferase activity. When isolated cholesteryl ester transfer protein from human plasma was included in the reaction mixture, cholesteryl ester was transported to sphingomyelin-cholesterol liposomes, with associated release of transferase from product inhibition. Cholesteryl ester incorporated directly into the liposomes or synthesized from free cholesterol via the transferase reaction was equally transferred to sphingomyelin acceptor liposomes, indicating that the cholesteryl ester in these particles formed a single miscible pool for transfer.