Activity of cholesterol in human gallbladder bile in relation to nucleation of cholesterol monohydrate crystals

To examine the hypothesis that the chemical activity of cholesterol molecules reflects the amount of cholesterol phasing out from bile associating with cholesterol monohydrate crystal nucleation, the cholesterol activities in human gallbladder biles from cholesterol gallstone patients, either untreated or treated with ursodeoxycholic acid, and from gallstone-free patients were determined in relation to the nucleation time and vesicular lipid composition. The cholesterol activity (nmol/disc/h) determined by the polyethylene disc uptake method was higher in the untreated gallstone group than the gallstone-free group (P less than 0.05) and the ursodeoxycholic acid treated group (P less than 0.01). The cholesterol activity correlated negatively with the nucleation time (P less than 0.01) and positively with both the vesicular cholesterol concentration (P less than 0.05) and the cholesterol/phospholipid ratio in vesicles (P less than 0.05). After the separation of vesicles from micelles by gel filtration, the cholesterol activity in the vesicular phase was found to be similar to that in the micellar phase. Interestingly, both the activities of cholesterol in the vesicular and micellar phases were significantly higher in the untreated gallstone group than in the gallstone-free group (P less than 0.05). These results suggest that cholesterol activity represents the amount of thermodynamically unstable cholesterol in bile.