Binding, uptake, and metabolism of chylomicron remnants by hepatocytes from control and chronic ethanol-fed rats.
Chylomicron remnants, but not lymph chylomicrons, showed a receptor-dependent high affinity saturable binding to normal rat hepatocytes. The Scatchard analysis of the specific binding data showed a high affinity binding site for the remnants with a dissociation constant of 0.61 nM, assuming a molecular weight of 50 X 10(6) for chylomicron remnants. Based on the heparin-releasable bound radioactivity, approximately 80% of the bound remnants seemed to be internalized. The binding process was markedly inhibited by pronase as well as by protein synthesis inhibitors. Competitive binding studies revealed that the order of competition for the binding of labeled remnants by homologous unlabeled lipoproteins was remnants greater than chylomicrons greater than very low density lipoproteins greater than high density lipoproteins. Human low density lipoproteins showed virtually no competition. Studies on the catabolism of triacylglycerol moiety of the remnants showed that 15.2% of the 14C label in the triacylglycerol moiety of the remnants was catabolized by the hepatocytes to 14CO2 due to specific interaction. This amounted to 93% of the total 14CO2 evolution. This was in sharp contrast to the catabolism of the triacylglycerol moiety of very low density lipoproteins from human and rat, where most of the 14CO2 evolution was due to pathways associated with nonspecific binding. Chronic ethanol feeding caused a 29% (p less than 0.02) decrease in the dissociation constant of the high affinity binding site of the liver cell for the remnants, whereas the extent of internalization was decreased by 19% (p less than 0.01) as compared to the pair-fed control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002914:Chylomicrons / Q000378:metabolism*; D005235:Fatty Liver, Alcoholic / Q000209:etiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002914:Chylomicrons; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL