CHOLESTEROL CRYSTALLIZATION-PROMOTING ACTIVITY OF AMINOPEPTIDASE-N ISOLATED FROM THE VESICULAR CARRIER OF BILIARY LIPIDS

Different hydrophobic glycoproteins are associated to native biliary v esicles, which are the major carrier of biliary cholesterol. Some of t hese proteins promote cholesterol crystallization, a key step in chole sterol gallstone formation. This study was specifically conducted to i dentify the 130 kDa biliary vesicle-associated glycoprotein and to det ermine 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 anti bodies raised against aminopeptidase-N allowed us to determine its con centration in human hepatic bile, which varied from 17.3 to 57.6 mug/m l. Aminopeptidase-N showed a concentration-dependent cholesterol cryst allization activity when it was added to supersaturated model bile at a concentration range usually found in native bile. Because of this pr omoting effect on in vitro cholesterol crystal formation, we suggest t hat biliary aminopeptidase-N may play a critical role in the pathogene sis of cholesterol gallstone disease.