PathwayStep1241 PathwayStep1242 PathwayStep1243 PathwayStep1247 PathwayStep1246 PathwayStep1245 PathwayStep1244 PathwayStep1248 CETP-mediated lipid exchange: LDL gains cholesterol ester apolipoprotein(a) + LDL => Lp(a) LDL + LDLR => LDL:LDLR complex Internalization of LDL:LDLR complex (LDLRAP1-dependent) Internalization of LDL:LDLR complex (LDLRAP1-independent) Movement of LDL:LDLR complex to early endosome LDLR:LDL complex => LDLR + LDL Recycling of LDLR to plasma membrane LDL endocytosis Authored: D'Eustachio, P, 2007-04-30 14:17:00 Edited: D'Eustachio, P, 2006-02-20 18:35:05 GENE ONTOLOGYGO:0006898 LDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipids. LDL complexes contain single molecules of apoB-100, but their content of lipids is variable (Chapman et al. 1988; Mateu et al. 1972; Tardieu et al. 1976). High levels of LDL in the blood are strongly correlated with increased risk of atherosclerosis, and recent studies have raised the possibility that this risk is further increased in individuals whose blood LDL population is enriched in high-density (low lipid content) LDL complexes (Rizzo and Berneis 2006). The LDL complex annotated here is given a lipid composition that is the average of those measured in the studies by Chapman, Mateu, Tardieu and their colleagues.<p>Annotation of LDL biology in Reactome to date is largely centered on the process of LDL endocytosis. As outlined in the figure below, extracellular low density lipoprotein (LDL) complexes bind to LDL receptors associated with coated pits at the cell surface (a), forming complexes that are internalized and passed via clathrin-coated vesicles (b) to endosomes (c), where they dissociate. The LDL particles move into lysosomes (d) and are degraded while the LDL receptors are returned to the cell surface (e). 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.<p>Familial hypercholesterolemia due to mutations affecting the LDL receptor (or, rarely, the apolipoprotein B-100 (apoB-100) component of LDL or the LDLRAP1 accessory protein involved in receptor uptake into clathrin-coated vesicles) is one of the commonest human genetic diseases, affecting approximately one person in 500 in many populations worldwide (Hobbs et al. 1990; Jeon and Blacklow 2005). LDL-mediated lipid transport Pubmed15952897 Pubmed16371404 Pubmed184289 Pubmed2088165 Pubmed3392462 Pubmed4342194 Reactome Database ID Release 43171052 Reactome, http://www.reactome.org ReactomeREACT_6934