title: Cholesterol crystallization-promoting activity of aminopeptidase-N isolated from the vesicular carrier of biliary lipids.
abstract: Different hydrophobic glycoproteins are associated to native biliary vesicles, which are the major carrier of biliary cholesterol. Some of these proteins promote cholesterol crystallization, a key step in cholesterol gallstone formation. This study was specifically conducted to identify the 130 kDa biliary vesicle-associated glycoprotein and to determine its in vitro effect on the cholesterol crystal formation time. The 130 kDa vesicular glycoprotein was identified as aminopeptidase-N by amino acid sequencing and specific enzymatic assay. Polyclonal antibodies raised against aminopeptidase-N allowed us to determine its concentration in human hepatic bile, which varied from 17.3 to 57.6 micrograms/ml. Aminopeptidase-N showed a concentration-dependent cholesterol crystallization activity when it was added to supersaturated model bile at a concentration range usually found in native bile. Because of this promoting effect on in vitro cholesterol crystal formation, we suggest that biliary aminopeptidase-N may play a critical role in the pathogenesis of cholesterol gallstone disease.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Núñez
authors.forename: L
authors.initials: L
authors.lastname: Amigo
authors.forename: A
authors.initials: A
authors.lastname: Rigotti
authors.forename: L
authors.initials: L
authors.lastname: Puglielli
authors.forename: G
authors.initials: G
authors.lastname: Mingrone
authors.forename: A V
authors.initials: AV
authors.lastname: Greco
authors.forename: F
authors.initials: F
authors.lastname: Nervi
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000201:enzymology*; D018826:CD13 Antigens; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D006023:Glycoproteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008055:Lipids / Q000032:analysis*; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D013552:Swine
chemical_list: D006023:Glycoproteins; D008055:Lipids; D002784:Cholesterol; D000626:Aminopeptidases; D018826:CD13 Antigens