Isolation and characterization of a cholesterol crystallization promoter from human bile

Masato Abel, Paul Kawczak, Hannu Nuutinen, Alan Langnas, Joar Svanvik, R. Thomas Holzbach

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Background: Recent studies on the pathogenesis of cholesterol gallstone disease have focused on the potential importance of an imbalance between biliary proteins having either inhibitory or promoting activities on nucleation and/or growth of cholesterol crystals as the initial stage in stone formation. The current study describes the purification and partial characterization of a 42-kilodalton biliary glycoprotein that shows concentration-dependent cholesterol crystallization-promoting activity. Methods: Chromatographie methods were used for separation and purification. Characterization steps included electrophoresis, deglycosylation, amino acid and carbohydrate analysis, and activity analysis by crystal growth assay. Results: The 42-kilodalton purified glycoprotein is an extensively glycosylated (37%) monomer with an acidic isoelectric point (pl < 4.1) that is probably based on the sialic acid content of the carbohydrate moiety. Enzymatic N-deglycosylation removes the carbohydrate moiety and inactivates the promoting activity. Furthermore, enzymatic proteolysis results in both its complete structural degradation and functional inactivation. Although the glycoprotein was isolated from normal human gallbladder biles, its presence in gallstone-associated samples is clearly shown. Conclusions: This report outlines biochemical features of a human biliary glycoprotein that may be of major pathophysiological significance in gallstone disease.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalGastroenterology
Volume104
Issue number2
DOIs
StatePublished - Feb 1993

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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