Efflux and Plasma Transport of Biosynthetic Sterols

The pathway of cholesterol biosynthesis has many steps, producing several intermediates. Some of the intermediates, such as lanosterol, zymosterol and desmosterol, are delivered to the plasma membrane, and are available for efflux and entry into the pathway of reverse sterol transport. Our studies with CHO and other extrahepatic cells suggest that these intermediates constitute the majority of biosynthetic sterol released to HDL; however, we see very little release from liver-derived cell lines, which make mainly cholesterol. Interestingly, we find that one of the intermediates, desmosterol, is released from cells three times more efficiently than cholesterol to extracellular sterol acceptors. This release may be an important mechanism in extrahepatic cells to prevent the pathology that is associated with the build-up of intermediates in cells and in tissues. In this chapter, we review what is known about biosynthetic sterols and their transport within cells, and summarize our data on their release to extracellular acceptors.