Emulsification of Cholesterol in Bile Salt Micelles:relevance For Cholesterol Absorption

Abstract

A high level of cholesterol in the blood is associated with predisposition for cardiac diseases and is one of the major human health problems[1]. Some cholesterol is synthesized in the liver and a significant amount is also absorbed from dietary cholesterol at the small intestinal brush border membranes. Dietary cholesterol is first emulsified in mixed micelles of bile salts (BS) and fatty acids (FA) and the currently accepted mechanism suggests that absorption involves the interaction between the mixed micelles and the apical membrane of brush border cells where passive mechanisms play a significant role[2]. However, the detailed mechanism and the dependence on the dietary mixture of lipids are far from being completely understood. In most studies, mixtures of BS and FA have been used and the distribution of cholesterol between different phases and/or the in vitro cholesterol intake has been measured[3]. The complexity of the systems studied precludes the interpretation of the effect of each component in the process. Here we present the study of the solubilization of a cholesterol analogue, Deydroergosterol, in micelles of glycocholic acid and glycochenodeoxycholic acid (most abundant BS in the upper intestine[3]) followed by fluorescence. We develop a kinetic model to describe the rate of sterol emulsification and its maximum solubility in the BS micelles. The study was also performed with cholesterol labeled with C13 in carbon 4 in the sterol ring and followed by C13 NMR Spectroscopy. From preliminary results we can identify and quantify the emulsified cholesterol in the BSM at a chemical shift of 41.6 ppm that is well separated from the C13 NMR resonances of BS[4]. From the data obtained we obtain the cholesterol saturation index and the kinetic profile for the solubilization of cholesterol in the BS micelles.