Cholesterol monomer activity and its role in understanding cholesterol saturation and crystallization

Cholesterol in bile has been linked to the incidence of gallstone disease through the concept of supersaturation as measured by the cholesterol saturation index. The latter is a linear function of cholesterol concentration and is based on the assumption that all cholesterol in bile is solubilized and transported in bile salt-lecithin mixed micelles and in bile salt simple micelles. In light of the discovery of the cholesterol-lecithin vesicles as significant cholesterol carriers, there is a need to reevaluate this old concept. This study examined the feasibility of the silicone polymer uptake method for the direct determination of the cholesterol thermodynamic activity in model bile systems. In cases of unsaturation and near saturation, a linear relationship was observed between the cholesterol concentration in the silicone polymer at equilibrium and the cholesterol saturation index (the cholesterol concentration in the aqueous micellar solution at equilibrium/cholesterol monohydrate solubility in the same medium) for taurocholate and taurochenodeoxycholate systems either containing or not containing lecithin. In taurocholate-lecithin solutions supersaturated with cholesterol, the linear relationship continued to hold up to the point where vesicles started to form. Vesicle formation initiated a negative deviation from linearity. At constant lecithin concentration, the cholesterol thermodynamic activity at which vesicle formation began was a function of the taurocholate/lecithin ratio; the larger the taurocholate/lecithin ratio, the higher the cholesterol thermodynamic activity for the onset of vesicle formation.(ABSTRACT TRUNCATED AT 250 WORDS)