1999/01/01 by Robert W. Mahley, Zhong-Sheng Ji · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · Chemistry · #Diabetes, Cardiovascular Risks, and Lipoproteins #Lipid metabolism and disorders #Lipid metabolism and biosynthesis #Chylomicron #Apolipoprotein E #Catabolism #Apolipoprotein B #Chemistry #Lipoprotein lipase #Cell biology #Receptor #Perisinusoidal space #LDL receptor #Lipoprotein #Internal medicine #Endocrinology #Biochemistry #Biology #Hepatocyte #Very low-density lipoprotein #Cholesterol #Metabolism #In vitro #Enzyme #Medicine
paper · doi:10.1016/s0022-2275(20)33334-4
openalex publication_date 1999/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The plasma clearance of intestinally derived remnant lipoproteins by the liver is a process that likely involves three steps. Our model suggests that the initial rapid clearance by the liver begins with sequestration of the remnants within the space of Disse, where apolipoprotein E secreted by hepatocytes enhances remnant binding and uptake. Heparan sulfate proteoglycans (HSPG), which are also abundant in the space of Disse, mediate this enhanced binding. Next, the remnants undergo further processing in the space of Disse by hepatic and lipoprotein lipases, which may also serve as ligands mediating remnant uptake. The final step, endocytosis by hepatocytes, appears to be mediated, at least in part, by the low density lipoprotein (LDL) receptor and by the LDL receptor-related protein (LRP). Cell-surface HSPG play a critical role in remnant uptake, not only in the important initial sequestration or capture step in the space of Disse, but also as an essential or integral component of the HSPG-LRP pathway. In addition, HSPG appear to function alone as a receptor and display unique handling properties for specific isoforms of apolipoprotein E.