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Biosynthesis of Cholesterol, Steroids, and Isoprenoids:- Cholesteryl Esters Enter Cells by Receptor-Mediated Endocytosis

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  p824-825

2026-06-20

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Biosynthesis of Cholesterol, Steroids, and Isoprenoids:- Cholesteryl Esters Enter Cells by Receptor-Mediated Endocytosis

Each LDL particle in the bloodstream contains apoB 100, which is recognized by specific surface receptor proteins, LDL receptors, on cells that need to take up cholesterol. The binding of LDL to an LDL receptor initiates endocytosis, which conveys the LDL and its receptor into the cell within an endosome (Fig. 21–42). The endosome eventually fuses with a lysosome, which contains enzymes that hydrolyze the cholesteryl esters, releasing cholesterol and fatty acid into the cytosol. The apoB-100 of LDL is also degraded to amino acids that are released to the cytosol, but the LDL receptor es capes degradation and is returned to the cell surface, to function again in LDL uptake. ApoB-100 is also present in VLDL, but its receptor-binding domain is not avail able for binding to the LDL receptor; conversion of VLDL to LDL exposes the receptor-binding domain of apoB-100. This pathway for the transport of cholesterol in blood and its receptor-mediated endocytosis by target tissues was elucidated by Michael Brown and Joseph Goldstein.

Cholesterol that enters cells by this path may be incorporated into membranes or reesterified by ACAT (Fig. 21–38) for storage within cytosolic lipid droplets. Accumulation of excess intracellular cholesterol is pre vented by reducing the rate of cholesterol synthesis when sufficient cholesterol is available from LDL in the blood. The LDL receptor also binds to apoE and plays a significant role in the hepatic uptake of chylomicrons and VLDL remnants. However, if LDL receptors are un available (as, for example, in a mouse strain that lacks the gene for the LDL receptor), VLDL remnants and chylomicrons are still taken up by the liver even though LDL is not. This indicates the presence of a back-up system for receptor-mediated endocytosis of VLDL remnants and chylomicrons. One back-up receptor is lipoprotein receptor-related protein (LRP), which binds to apoE as well as to a number of other ligands.