Isolation of a human biliary glycoprotein inhibitor of cholesterol crystallization

Gastroenterology. 1993 Feb;104(2):527-38. doi: 10.1016/0016-5085(93)90423-a.


Background: About 50% of populations in developed countries have bile supersaturated with cholesterol, which is a major risk factor for cholesterol gallstone formation. Despite the prevalence of supersaturated bile, only about 10% of these populations develop gallstones. The existence of a biliary protein that inhibits cholesterol crystallization was hypothesized to explain this discrepancy. This report outlines the purification and characterization of such a human biliary glycoprotein.

Methods: Chromatographic methods were used for separation and characterization. Additional steps included activity analysis by crystal growth assay, electrophoresis, and deglycosylation.

Results: The glycoprotein consists of a heterodimer, M(r) of 120 kilodalton, with subunits of M(r) of 63 kilodalton and 58 kilodalton. Each of the subunits is characterized by an isoelectric point of 6.6 and shows comparable inhibitory activity. Deglycosylation of the subunits show that they share a similar polypeptide backbone (M(r) of 35 kilodalton) based upon a highly similar amino acid profile. This suggests that differential subunit glycosylation alone may account for the apparent heterodimeric structure.

Conclusions: No other human biliary glycoprotein has been found thus far that shows cholesterol crystal growth-inhibiting activity. Thus, it may be of importance in preventing gallstone formation in healthy populations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / analysis
  • Bile / chemistry*
  • Cholelithiasis / etiology
  • Cholesterol / metabolism*
  • Chromatography, Affinity
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Crystallization
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Glycoproteins / analysis
  • Glycoproteins / isolation & purification*
  • Glycoproteins / pharmacology
  • Glycosylation
  • Humans


  • Amino Acids
  • Glycoproteins
  • Cholesterol