Metabolism of Free and Esterified Cholesterol and Apolipoproteins of Plasma Low and High Density Lipoproteins

We studied the patterns of equilibration of free and esterified cholesterol between lipoprotein fractions of plasma separated by heparin-Mn2+ and of their disappearance from plasma and appearance in liver and bile. Free or esterified [4-14C]cholesterol in low density lipoproteins (LDL) and [7(n)-3H]cholesterol in high density lipoproteins (HDL2 or HDL3) were incubated together with plasma or injected simultaneously into squirrel monkeys. The isotope was alternated for successive experiments. Free cholesterol was equilibrated completely between lipoprotein classes within 30-45 min, but esterified cholesterol was not completely equilibrated within 2 h. Within 10 min after the injection of lipoproteins that had labeled free cholesterol, the bile contained labeled free cholesterol and within 20 min labeled bile acids. Both biliary cholesterol and bile acids initially were enriched 5-10-fold with the isotope that was originally contained in plasma HDL. Hepatic cholesterol was less enriched than bile cholesterol with the isotope of HDL. There was much less incorporation of radioactivity into biliary cholesterol and bile acids after the injection of [7(n)-3H]cholesteryl esters in HDL2 or HDL3 and [4-14C]cholesterol esters in LDL than after labeled free cholesterol, and there was little preference for cholesterol from one lipoprotein class. Although cholesteryl esters were equilibrated slowly between lipoprotein classes, their overall rate of removal from plasma was identical to that for the apolipoproteins of 125I-labeled LDL and 125I-labeled HDL during the first 2 h after injection. Labeled free cholesterol initially disappeared from the plasma compartment several times more rapidly than the esterified form or the lipoprotein apolipoprotein. Thus, cholesteryl esters probably interact with cells as part of intact lipoproteins, since they are not exchanged with cellular cholesterol like plasma free cholesterol.