APOPROTEIN-B STRUCTURE AND RECEPTOR RECOGNITION OF TRIGLYCERIDE-RICH LOW-DENSITY-LIPOPROTEIN (LDL) IS MODIFIED IN SMALL LDL BUT NOT IN TRIGLYCERIDE-RICH LDL OF NORMAL SIZE

We compared the effect of lipid composition and particle size of trigl yceride-rich low density lipoprotein (LDL) upon apoprotein B conformat ion and binding to the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL made triglyceride-rich by in vit ro incubation with triglyceride emulsion and the neutral lipid transfe r protein (R-LDL); and (c) LDL from normolipidemic individuals made ac utely hypertriglyceridemic by intravenous infusion of 10% Intralipid ( IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had nor mal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased bindin g to the LDL receptor on human skin fibroblasts in studies at 4-degree s-C and reduced degradation at 37-degrees-C. Apoprotein B conformation was assessed by circular dichroism and by analyzing the immunoreactiv ity of different monoclonal antibodies. HTG-LDL but not R-LDL or IV-LD L showed a change in the CD spectra and a consistent decrease in the i mmunoreactivity of monoclonal antibody 3F5 (2.5-fold) which recognizes an epitope adjacent to the receptor binding domain of apoprotein B. T hese findings suggest that in triglyceride-rich LDL, the relative cont ent of neutral lipid in the core of LDL in the absence of changes in t he size of the particle does not significantly affect apoprotein B con formation or its affinity for the LDL receptor.