The influence of LP-X and other lipoproteins associated with hepatic dysfunction on the activity of lecithin:cholesterol acyltransferase.

A study was made of the in vitro effects of the abnormal serum lipoproteins associated with liver disease on the activity of the enzyme lecithin:cholesterol acyltransferase. At lipoprotein concentrations equivalent to those found in hepatic disease sera, the results indicate that: (1) LP-X levels greater than 2.5 mg/ml produced total inhibition of enzyme activity. (2) LP-X levels remained constant even up to 36 h incubation, despite active cholesterol esterification in the presence of LP-X concentrations less than 2.5 mg/ml. In addition, the specific activity of radiolabelled LP-X, and its electrophoretic properties remained unchanged after incubation showing that the molecule remained intact. (3) Low density lipoproteins other than LP-X stimulated the enzymes activity, but this effect was overcome by LP-X. (4) Additional concentrations of high density lipoproteins also produced enhancement of enzyme activity, but at higher levels inhibition was seen. LP-X prevented the enhancement of lecithin:cholesterol acyltransferase activity. (5) Small samples of pure LP-X, obtained with the minimum of physical manipulation, showed a complete absence of cholesterol ester and triacylglycerol from the molecule. The implications of these results are discussed, particularly in relation to other reports which have presented evidence that LP-X is a substrate for lecithin:cholesterol acyltransferase.