Plasma lipoprotein clearance

Stable Identifier
R-HSA-8964043
Type
Pathway
Species
Homo sapiens
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Circulating chylomicrons acquire molecules of apolipoproteins C and E and through interaction with endothelial lipases lose a large fraction of their triacylglycerol. These changes convert them to chylomicron remnants which bind to LDL receptors, primarily on the surfaces of liver cells, clearing them from the circulation (Redgrave 2004).
Most very-low-density lipoproteins (VLDL) are converted to low-density lipoproteins (LDL) (VLDL remodeling pathway). A small fraction are taken up by VLDL receptors on extrahepatic cells, as annotated here. Clearance of LDL from the blood involves binding to LDL receptors associated with coated pits at the cell surface, forming complexes that are internalized and passed via clathrin-coated vesicles to endosomes, where they dissociate. The LDL particles move into lysosomes and are degraded while the LDL receptors are returned to the cell surface. This process occurs in most cell types but is especially prominent in hepatocytes. It plays a major role in returning cholesterol from peripheral tissues to the liver (Hobbs et al. 1990).
Clearance of circulating HDL particles involves particle binding to cell-surface SR-BI receptors, particle disassembly with rlease of pre-beta HDL (Silver & Tall 2001), and uptake of the latter mediated by cell-surface CUBN:AMN complex (Kozyraki et al. 1999).
VLDLR internalization plays a clinically significant role in determining the efficiency of lipoprotein clearance from the blood (Poirier et al. 2008).

Literature References
PubMed ID Title Journal Year
2088165 The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein

Hobbs, HH, Brown, MS, Goldstein, JL

Annu Rev Genet 1990
18039658 The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2

Poirier, S, Mayer, G, Benjannet, S, Bergeron, E, Marcinkiewicz, J, Nassoury, N, Mayer, H, Nimpf, J, Prat, A, Seidah, NG

J. Biol. Chem. 2008
10371504 The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein

Kozyraki, R, Fyfe, JC, Kristiansen, M, Gerdes, C, Jacobsen, C, Cui, S, Christensen, EI, Aminoff, M, de la Chapelle, A, Krahe, R, Verroust, PJ, Moestrup, SK

Nat Med 1999
11561168 The cellular biology of scavenger receptor class B type I

Silver, DL, Tall, AR

Curr Opin Lipidol 2001
14748717 Chylomicron metabolism

Redgrave, TG

Biochem. Soc. Trans. 2004
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