The Formation of Cholesterol Esters with Rat Liver Enzymes

Abstract

The composition of liver cholesterol esters is the net resultant of several metabolic processes, including the uptake of chylomicron cholesterol esters originating in the intestinal tract (l), hydrolysis (2) and synthesis of cholesterol esters in the liver, and transport from the liver of cholesterol esters incorporated into plasma lipoproteins (3). Recent studies in viva have shown substantial hydrolysis within the liver of cholesterol esters derived from circulating chylomicrons (I). Additional investigations with rat liver homogenates have shown that the bulk of hydrolytic enzyme activity is present in the soluble fraction of the liver homogenate (2). The different fatty acid esters were hydrolyzed at different rates with the relatire rates of hydrolysis being cholesteryl oleate = linoleate > palmitate > stearate. No cofactors were required. In addition to this hydrolytic activity, studies extending back more than two decades have shown the presence of cholesterol-esterifying activity in rat liver preparations (4-9). Very little information is, however, available about the details of this esterification, except for the evidence of Mukherjee, Kunitake, and Alfin-Slater (8) that esterification proceeds by way of a reaction between cholesterol and a fatty acyl coenzyme A ester. The present study reports on experiments dealing with the formation of long chain fatty acid esters of cholesterol with rat liver preparations. A preliminary report of some of these findings has been published (10).