Binding of rat chylomicrons and their remnants to the hepatic low-density-lipoprotein receptor and its role in remnant removal.
Binding and uptake of rat chylomicrons of different metabolic stages by the hepatic low-density-lipoprotein (LDL) receptor were studied. Pure chylomicrons, characterized by apolipoprotein B-48 devoid of contaminating B-100, were labelled in their cholesteryl esters. Lymph chylomicrons and serum chylomicrons, enriched in apolipoprotein E and the C-apolipoproteins, bound poorly to rat hepatic membranes. In contrast, chylomicron remnants, containing the apolipoproteins B-48 and E, bound with high affinity. Specific binding of remnants was virtually completely competed for by LDL free of apolipoprotein E. In addition, in ligand blots both remnants and LDL associated with the same protein with an Mr characteristic of the LDL receptor. Uptake of remnants during a single pass through isolated perfused rat livers was decreased to about 50% by an excess of LDL. It is concluded that rat chylomicron remnants are a ligand of the hepatic LDL receptor. The much higher affinity as compared with LDL is mediated by apolipoprotein E but not B-48, and is inhibited by the C-apolipoproteins. This explains why serum chylomicrons are not taken up by the liver, whereas remnants are rapidly removed from the circulation. Results from experiments in vivo suggest that the LDL receptor makes an important contribution to the hepatic uptake of remnants and may be the principal binding site of the liver responsible for remnant removal.
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, West Germany.
E E
EE
Windler
J
J
Greeve
W H
WH
Daerr
H
H
Greten
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis; D002914:Chylomicrons / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007525:Isoelectric Focusing; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011973:Receptors, LDL / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis
D001053:Apolipoproteins; D002914:Chylomicrons; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol