MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN - SPECIFICITY OF LIPID-BINDING AND TRANSPORT

Microsomal triglyceride transfer protein (MTP) is a lipid transfer pro tein that is required for the assembly and secretion of very low densi ty lipoproteins by the liver and chylomicrons by the intestine. To fur ther elucidate the nature of the lipid molecule binding and transport site on MTP, we have studied the relative rates at which MTP transport s different lipid species. Assay conditions were chosen in which there were minimal changes in the physical properties of the substrate memb ranes so that transfer rates would reflect MTP-lipid interactions at a membrane surface. Lipid transport rates decreased in order of triglyc eride > cholesteryl ester > diglyceride > cholesterol > phosphatidylch oline. Changes in the hydrophobic nature of a lipid molecule by the ad dition of a fatty acid, modulated the ability of MTP to transport it. Addition of one acyl chain from diglyceride to triglyceride, lysophosp hatidylcholine to phosphatidylcholine, or cholesterol to cholesteryl e ster increased the rate of MTP-mediated transport 10-fold. In contrast , the lipid transport rate was insensitive to the changes in the struc ture or charge of the polar head group on phospholipid substrates. Zwi tterionic, net negative, or net positive charged phospholipid molecule s were all transported at a comparable rate. The ability of MTP to tra nsport lipids is strongly correlated to the binding of these lipids to MTP. Thus, MTP has a specific preference for binding and transporting nonpolar lipid compared with phospholipids, and within a class of lip id molecules, a decrease in polarity increases its tendency to be tran sported.