Apolipoprotein E structure and substrate and receptor-binding activities of triglyceride-rich human plasma lipoproteins in normo- and hypertriglyceridemia.
Cysteine-arginine interchanges along the primary sequence of human plasma apolipoprotein E (apoE) play an important role in determining its biological functions due to a high mutation frequency of cytosine in CGX triplet that codes 33 of 34 apolipoprotein arginine residues. The contribution of apoE secondary structure to apolipoprotein-lipid interaction is described. The significance of apolipoprotein in triglyceride synthesis, lipoprotein lipolysis, and receptor-mediated clearance of lipolytic remnants of triglyceride-rich lipoproteins is discussed as well. The metabolic flow of lipoproteins in normo- and hypertriglyceridemia can be described by separate compartments that contribute to lipoprotein interaction with at least six different receptors: 1) low density lipoprotein (LDL) receptor; 2) LDL receptor-related protein (LRP); 3) apoB(48) macrophage receptor for hypertriglyceridemic very low density lipoproteins (VLDL); 4) scavenger receptors; 5) VLDL receptor; 6) lipolysis-stimulated receptor. The contribution of the exposure of apoE molecules on the surface of triglyceride-rich particles sensitive both to lipolysis and plasma triglyceride content to the interaction with LDL receptor and LRP is emphasized.
National Research Center for Preventive Medicine, Moscow 101953, Russia. dergunov@img.ras.ru
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D001057:Apolipoproteins E / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D018110:Receptors, Lipoprotein / Q000097:blood / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D001057:Apolipoproteins E; D008074:Lipoproteins; D018110:Receptors, Lipoprotein; D014280:Triglycerides