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 across biological membranes via a mechanism involving enzymes anchored to membrane proteoglycans such as those found in the brush border of the 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, 7438-7442]. 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 increased 39-fold in the same time period, indicating that the enzyme-mediated uptake accounts for 10-fold greater ester synthesis than that from basal absorption. Kinetic analysis reveals that both enzyme-mediated and background absorption depend on taurocholate concentration and are second-order reactions more likely dependent on collision than diffusion. Other lipid-recognizing proteins such as pancreatic triglyceride lipase and the intestinal fatty acid binding protein are not stimulatory to intracellular cholesterol processing. Taken together, these data suggest that pancreatic cholesterol esterase and possibly other proteoglycan-binding extracellular enzymes of neutral lipid metabolism may facilitate movement of neutral lipids into the plasma membrane and direct them into functional intracellular sites.
Lopez-Candales
A
A
CV Therapeutics, California 94043.
Bosner
M S
MS
Spilburg
C A
CA
Lange
L G
LG
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D004951:Esterification; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D010179:Pancreas / Q000201:enzymology*; D002787:Sterol Esterase / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D013261:Sterols; D002784:Cholesterol; D002787:Sterol Esterase