The distribution of the biliary-anionic polypeptide fraction between cholesterol carriers in bile and its effect on nucleation.

The small (7 kD) biliary phospholipid and calcium binding polypeptide (anionic polypeptide fraction/calcium binding protein) has been found in higher concentrations in the bile of patients with pigment stones than in controls. In different model systems it was variously found to promote or retard cholesteral crystalization. In the present study we investigated its distribution between cholesterol carriers in bile and its effect on cholesterol crystalization in native and model biles. On gel chromatography anionic polypeptide fraction/calcium binding protein was found predominantly in three areas: in the vesicular fraction, in the non-vesicular lipid fraction and in another fraction unassociated with biliary lipids. It was much more concentrated in the vesicular than in the non-vesicular fraction, the mean anionic polypeptide fraction/phospholipid molar ratio being 219 +/- 181 vs. 30.4 +/- 16, respectively. Anionic polypeptide fraction/calcium binding protein was added at three dose levels, 0.14, 0.28, 0.42 mg/ml (representing approximately 18%-55% of the physiologic biliary concentration), to 19 human and five model biles. This did not produce any significant changes in the nucleation time. The addition of anionic polypeptide fraction/calcium binding protein at a dose level of 0.42 mg/ml to 13 different human biles did not induce changes in the distribution of cholesterol among its carriers. The present experiments do not support a role for anionic polypeptide fraction/calcium binding protein in the process of cholesterol nucleation in bile. Qualitative changes in the protein molecule, as demonstrated in other human secretions, cannot be excluded.