KINETICS AND INHIBITION OF LIPID EXCHANGE CATALYZED BY PLASMA CHOLESTERYL ESTER TRANSFER PROTEIN (LIPID TRANSFER PROTEIN)

The cholesteryl ester transfer protein-catalyzed cholesteryl ester tra nsfer is inhibited by two compounds identified by a large-scale screen ing of cholesterol backbone-containing molecules. Kinetic analysis sho ws that U-95,594, an amino steroid, inhibits competitively the cholest eryl ester transfer protein-catalyzed transfer of both cholesteryl est ers and triglycerides, as well from high-density lipoproteins as from synthetic microemulsions. In contrast, U-617, an organomercurial deriv ative of cholesterol, inhibits competitively the transfer of cholester yl ester from either donor but is without any effect on triglyceride t ransfer. In addition to the rapid, competitive inhibition of cholester yl ester transfer, U-617 also slowly and reversibly reacts with choles teryl ester transfer protein to produce an additional 10-fold decrease in cholesteryl ester transfer activity but, again, without effect on triglyceride transfer.