Turnover of individual cholesterol esters in human liver and plasma.

There are several lines of evidence which suggest that the liver is a major source of plasma cholesterol esters. First, eviscerated rats cannot maintain a normal concentration of cholesterol esters in the plasma (1); second, when isotopically labeled mevalonic acid is administered to rats, the specific radioactivity of the hepatic cholesterol esters initially exceeds that of the plasma cholesterol esters (2); and third, the perfusion of livers from cholesterol-fed rats leads to an increased secretion of cholesterol esters from the liver into the perfusate (3). Despite this, the composition of cholesterol esters in the liver and plasma is dissimilar, both in the rat (2, 3) and in man (4, 5). This has raised the question of whether an additional source of plasma cholesterol esters exists outside the liver. A transesterification reaction between free cholesterol and the beta fatty acid of lecithin has been demonstrated in plasma and could account for a portion of the plasma cholesterol esters (6, 7). Simultaneous esterification of cholesterol in liver and plasma could lead to the formation of cholesterol esters of differing composition. Some of the factors that govern the formation and composition of cholesterol esters have been determined in the rat. The turnover of cholesterol esters in rat liver and plasma is heterogeneous. The fractional turnover rate of plasma cholesteryl oleate is greater than that of the other esters (2) and may be related to the high degree of specificity for cholesteryl oleate formation by liver enzymes (8). When rats are fed cholesterol with different fatty acids, cholesteryl oleate accumulates in the * liver irrespective of the fatty acid fed, yet cho-lesteryl arachidonate remains the predominant ester in the plasma and is the major cholesterol ester secreted by the liver in the fasting rat (9). The heterogeneity of plasma cholesterol ester turnover found in the rat does not apply in man. Goodman (10) has demonstrated a similarity in the fractional turnover rates of individual cholesterol esters within a given class of plasma lipo-proteins. This finding has been confirmed by Nestel, Couzens, and Hirsch (5), who have shown this to apply equally in men with low and high plasma cholesterol concentrations. This paper reports further studies in man in which the incorporation of radioactivity into the individual cholesterol esters of liver and plasma has been measured. We have compared the specific radioactivities of individual esters in liver and plasma in order to determine, first, whether …