Metabolism of apolipoprotein E in plasma high density lipoproteins from normal and cholesterol-fed rats

High density lipoproteins of rat blood plasma were labeled in vitro with radioiodinated apolipoprotein E and biologically with [3H]cholesteryl esters. These two components, present in high density lipoproteins separated from serum of normal or cholesterol-fed rats by molecular sieve chromatography, were removed slowly from perfused livers and the labeled apolipoprotein E was also removed slowly from the blood of intact rats. However, when labeled serum was subjected to ultracentrifugation at a density of 1.21 g/ml before the floating apolipoprotein E-labeled high density lipoproteins were separated by chromatography, the labeled protein was rapidly removed from the blood of intact rats by uptake into the liver. About one-half of the labeled apolipoprotein E associated with high density lipoproteins was dissociated during ultracentrifugation, but most of it reassociated with the these lipoproteins when the floating lipoproteins were remixed with the sedimented serum proteins. The apolipoprotein E in such reassociated high density lipoproteins was removed from the blood of intact rats at the slow rate observed when the high density lipoproteins were separated chromatographically from whole serum. About 90% of the labeled apolipoprotein E in uncentrifuged or centrifuged high density lipoproteins was shown by affinity chromatography to be associated with particles containing apolipoprotein A-I. Rapid hepatic uptake of apolipoprotein E in centrifuged high density lipoproteins may result from an altered conformation of the apolipoprotein E on the particle surface.