title: Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile.
abstract: Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human bile was mixed with model bile and the effect on the distribution of cholesterol and phospholipid between mixed micelles and phospholipid/cholesterol vesicles was studied by means of density gradient ultracentrifugation. The nucleation-promoting activity containing fraction induced a transfer of cholesterol and phospholipid from the micellar to the vesicular phase. This led to a decrease in the density of the vesicular fraction. We have also studied the effect of promoting activity on the nucleation time of an isolated vesicle fraction. A decrease of the nucleation time of 10.7 +/- 1.3 to 2.3 +/- 0.3 days was observed. In conclusion, a concanavalin A binding protein fraction from human bile stimulated cholesterol nucleation via a double effect; it increased the amount of vesicular cholesterol and phospholipid, and it also directly induced nucleation of cholesterol from the vesicles.
authors.affiliation: Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: A K
authors.initials: AK
authors.lastname: Groen
authors.forename: R
authors.initials: R
authors.lastname: Ottenhoff
authors.forename: P L
authors.initials: PL
authors.lastname: Jansen
authors.forename: J
authors.initials: J
authors.lastname: van Marle
authors.forename: G N
authors.initials: GN
authors.lastname: Tytgat
mesh_terms: D001646:Bile / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol; D002794:Choline / Q000032:analysis; D003208:Concanavalin A / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D006801:Humans; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000032:analysis; D012995:Solubility
chemical_list: D005230:Fatty Acids, Nonesterified; D010713:Phosphatidylcholines; D003208:Concanavalin A; D002784:Cholesterol; D002794:Choline