CHOLESTEROL TRANSPORT FUNCTION OF PANCREATIC CHOLESTEROL ESTERASE - DIRECTED STEROL UPTAKE AND ESTERIFICATION IN ENTEROCYTES

We have recently hypothesized that neutral lipids can, in part, move a cross biological membranes via a mechanism involving enzymes anchored to membrane proteoglycans such as those found in the brush border of t he enterocyte [Bosner, M. S., Gulick, T., Riley, D. J. S., Spilburg, C . A., & Lange, L. G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7438-744 2]. Present results now show a subsequent, essential protein-mediated sorting of neutral lipids for further intracellular metabolism. Thus, in the absence of enzyme, 0.002 pmol of cellular ester appeared after 2 h, and its level increased only 3.5-fold after 12 h. However, in the presence of cholesterol esterase, the level of cholesterol ester incr eased 39-fold in the same time period, indicating that the enzyme-medi ated uptake accounts for 10-fold greater ester synthesis than that fro m basal absorption. Kinetic analysis reveals that both enzyme-mediated and background absorption depend on taurocholate concentration and ar e second-order reactions more likely dependent on collision than diffu sion. Other lipid-recognizing proteins such as pancreatic triglyceride lipase and the intestinal fatty acid binding protein are not stimulat ory to intracellular cholesterol processing. Taken together, these dat a suggest that pancreatic cholesterol esterase and possibly other prot eoglycan-binding extracellular enzymes of neutral lipid metabolism may facilitate movement of neutral lipids into the plasma membrane and di rect them into functional intracellular sites.