J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 42, 1273-1281, August 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Cholesterol crystallization in model biles: effects of bile salt and phospholipid species composition

Antonio Moschettaa,b, Gerard P. vanBerge-Henegouwena, Piero Portincasab, Giuseppe Palascianob, and Karel J. van Erpecuma
a Gastrointestinal Research Unit, Departments of Gastroenterology and Surgery, University Medical Center, 3508 GA Utrecht, The Netherlands
b Internal Medicine, Department of Internal and Public Medicine, University Hospital of Bari, Bari, Italy

Correspondence to: Karel J. van Erpecum, To whom correspondence should be addressed., k.j.vanerpecum{at}azu.nl (E-mail)

Cholesterol in human bile is solubilized in micelles by (relatively hydrophobic) bile salts and phosphatidylcholine (unsaturated acyl chains at sn-2 position). Hydrophilic tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all decrease cholesterol crystal-containing zones in the equilibrium ternary phase diagram (van Erpecum, K. J., and M. C. Carey. 1997. Biochim. Biophys. Acta. 1345: 269;–282) and thus could be valuable in gallstone prevention. We have now compared crystallization in cholesterol-supersaturated model systems (3.6 g/dl, 37°C) composed of various bile salts as well as egg yolk phosphatidylcholine (unsaturated acyl chains at sn-2 position), dipalmitoyl phosphatidylcholine, or sphingomyelin throughout the phase diagram. At low phospholipid contents [left two-phase (micelle plus crystal-containing) zone], tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all enhanced crystallization. At pathophysiologically relevant intermediate phospholipid contents [central three-phase (micelle plus vesicle plus crystal-containing) zone], tauroursodeoxycholate inhibited, but dipalmitoyl phosphatidylcholine and sphingomyelin enhanced, crystallization. Also, during 10 days of incubation, there was a strong decrease in vesicular cholesterol contents and vesicular cholesterol-to-phospholipid ratios (~1 on day 10), coinciding with a strong increase in crystal mass. At high phospholipid contents [right two-phase (micelle plus vesicle-containing) zone], vesicles were always unsaturated and crystallization did not occur.

Strategies aiming to increase amounts of hydrophilic bile salts may be preferable to increasing saturated phospholipids in bile, because the latter may enhance crystallization. — Moschetta, A., G. P. vanBerge-Henegouwen, P. Portincasa, G. Palasciano, and K. J. van Erpecum. Cholesterol crystallization in model biles: effects of bile salt and phospholipid species composition. J. Lipid Res. 2001. 42: 1273;–1281.

Supplementary key words: crystals, dialysis, intermixed micellar/vesicular bile salt concentration, micelles, phosphatidylcholine, sphingomyelin, taurocholate, taurodeoxycholate, tauroursodeoxycholate, ultrafiltration, vesicles


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