Role of Bile Salts in Activity of Cholesterol Esterase

Abstract

Conclusions

The data on the different bile salts suggest that several aspects of the structure of the bile salt molecule are involved in their effects on cholesterol esterase activity. Firstly, taurocholic acid has a distinctly greater effect than either glycocholic or the unconjugated cholic acid (the latter in the esterifying system only). Secondly, conjugation with glycine inhibits the effect of cholic acid. Thirdly, free taurine and glycine have no influence on the effect of cholic acid, i.e. the effects of taurocholic and glycocholic acids are due to the intact molecules. Fourthly, in the series of unconjugated acids the degree of effect was greatest with cholic acid which has 3 hydroxyl groups in the molecule and the effect decreased with the decreasing number of hydroxyl groups until with dehydrocholic, which has no hydroxyl groups, there was no effect. The results clearly demonstrate that both the hydroxyl groups and the carboxyl group, free or conjugated, are involved in the effect of bile salts on cholesterol esterase activity.

From the previous work, reviewed above, the bile salt effect does not appear to be related to emulsifkation of the substrate or the stabilization of the enzyme. The present findings on the interrelationships of cholesterol and bile salt concentration suggest some type of combination between cholesterol and bile salt. The data on the esterincation system are especially significant. They indicate that 1 molecule of bile salt is associated with 1 molecule of cholesterol in the reaction with the fatty acid. It seems likely that the levels of activity observed were related to the concentration of a complex between cholesterol and bile salts rather than the concentration of either of the compounds, independently. In the hydrolytic system there was some effect of bile salt concentration above a 1:1 molar ratio with the cholesterol ester. However, the results are in accord with the hypothesis of complex formation between cholesterol or cholesterol ester and bile salt. If the mechanism of the bile salt effect is complex formation, the differences between the different bile salts could be due either to ease of complex formation or a specificity of cholesterol esterase related to the structure of the bile salt molecule.