Serum Cholesterol Esterification in Human Liver Disease: Role of Lecithin-Cholesterol Acyltransferase and Cholesterol Ester Hydrolase

Abstract

Serum cholesterol esters in man are largely formed intravascularly by lecithin-cholesterol acyltransferase (LCAT), a circulating enzyme of hepatic origin. Esterification of serum cholesterol in vitro is normally equatable with LCAT activity, but in patients with liver disease it has been suggested that the damaged liver releases cholesterol ester hydrolase into the circulation, so that serum net cholesterol-esterifying activity reflects a balance between LCAT and hydrolase activities rather than LCAT alone. To assess the validity of this hypothesis, we simultaneously assayed net cholesterol-esterifying activity and LCAT in sera from 25 patients with parenchymal liver disease, the former by a colorimetric method and the latter by a 14 C-isotopic assay. There was close agreement between the two esterification rates ( r = 0.89, P P r ≅ 0.7, P 14 C cholesterol linoleate into autologous serum substrate. Electrophoretic and radiochromatographic analysis of substrate sera suggested that most of the 14 C-ester was incorporated into lipoproteins, and validity of the assay was confirmed by its ability to detect known cholesterol ester hydrolase activity in dog serum and hog pancreatic extract. Serum hydrolytic activity was sought in 13 of the patients, but none was detected even in those with severe hepatic disease. These studies, therefore, revealed neither direct nor indirect evidence of circulating cholesterol ester hydrolase in patients with parenchymal liver disease, although its rare occurrence has not been completely excluded. Low LCAT activity can entirely account for the impaired in vitro cholesterol esterification of hepatic disease and probably contributes to the cholesterol ester derangements seen in vivo.