The significance of apolipoprotein E structure to the metabolism of plasma triglyceride-rich lipoproteins.
In this paper we analyse the structural organization of human apolipoprotein E (apoE) at the surface of triglyceride (TG)-rich lipoproteins, in relation to the metabolic pathway of these particles. ApoE acts as a receptor-binding ligand at the surface of chylomicrons and VLDL (very low density lipoproteins). The degree of exposure of apoE at the surface of lipoproteins and its affinity for the receptor both determine the uptake and catabolism of these lipoproteins. ApoE and/or apoB100, the major apolipoprotein constituent of LDL, contribute to the interaction of lipoproteins with five different cellular receptors: 1) the low density lipoprotein (LDL) receptor; 2) the LDL receptor-related protein (LRP); 3) the macrophage receptor for hypertriglyceridemic VLDL; 4) the scavenger receptor; 5) the VLDL receptor. The degree of exposure of apoE at the surface of normo- and hyperlipidemic VLDL can modulate their uptake by the LDL receptor. Normolipidemic VLDL are poorly recognized by the LDL receptor whereas hypertriglyceridemic VLDL are cleared more efficiently through this pathway. On the other hand, the extent of apoE self-association, which is dependent upon the degree of hydrolysis of the TG-rich particles, can control their interaction with the LDL-receptor related protein. The lateral organization of apoE at the surface of TG-rich particles, its interaction with other apoproteins and its extent of self-association might therefore be important factors in the clearance of these lipoproteins. Finally, structural defects of apoE might result in an impaired interaction of apoE-containing lipoproteins with these receptors and lead to the development of atherogenic dyslipidemias.
Dergunov
A D
AD
Biochemistry Department, National Research, Centre for Preventive Medicine, Moscow, Russia.
Rosseneu
M
M
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry* / Q000378:metabolism; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D002914:Chylomicrons; D008024:Ligands; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor