The hydrolysis of long-chain fatty acid esters of cholesterol with rat liver enzymes.

The liver plays a central role in the metabolism of cholesterol absorbed from the gastrointestinal tract. Most of this cholesterol is transported as esterified cholesterol in chylomicrons (2, 3)) by way of intestinal lymph. Recent experiments in this laboratory have demonstrated that soon after the intravenous injection into rats of chylomicrons containing labeled cholesterol esters, almost 90% of the labeled cholesterol was found in the liver, as esterified cholesterol (4). Slow hydrolysis of the esterified cholesterol then occurred within the liver, followed by gradual redistribution of the labeled cholesterol to other tissues. These findings indicate that liver hydrolysis of chylomicron cholesterol ester is an important component of the metabolism of cholesterol. In addition, the liver participates in the metabolism of esterified cholesterol in other ways. Evidence exists that the liver may be the primary source of plasma cholesterol esters (5), and that the individual fatty acid esters of cholesterol are differently metabolized within the liver (6). Very little information exists concerning the hydrolysis of longchain fatty acid esters of cholesterol by liver enzymes. Nieft and Deuel (7) demonstrated net hydrolysis of cholesteryl palmitate, with the use of a saline extract of rat liver homogenates and a 21..hour incubation. Subsequent investigators, however, have employed short-chain esters, particularly cholesteryl acetate, to study liver cholesterol esterase activity (8,9). It is shown below that this is not a satisfactory substrate for the study of the hydrolysis of long-chain fatty acid esters of cholesterol. The present study reports the hydrolysis of long-chain fatty acid esters of cholesterol with enzymes present in the microsomal and soluble fractions of rat liver.