TY - JOUR
T1 - Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones
AU - Harvey, P. Robert C.
AU - Somjen, Giora
AU - Lichtenberg, Marc S.
AU - Petrunka, Connie
AU - Gilat, Tuvia
AU - Strasberg, Steven M.
N1 - Funding Information:
The authors would like to thank Mrs. JoAnn Gold for her secretarial assistance and Mr. Doug Holmyard for his preparation of the results of the electron photomicrography. This study was supported by the Physicians’ Services Incorporated and the Medical Research Council of Canada. P.R.C.H. is a Career Scientist for the Ontario Ministry of Health, Health Personnel Development Program.
PY - 1987/9/25
Y1 - 1987/9/25
N2 - Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days ± 0.7) as from patients with stones (2.4 days ± 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.
AB - Bile was obtained from patients with and without cholesterol gallstones at surgery. Biliary vesicles were separated from micelles by gel filtration. The cholesterol/phospholipid ratio in vesicles was much higher than in micelles. Cholesterol crystals nucleated from vesicular fractions, but nucleation from the micellar fractions was slow or did not occur at all. Cholesterol nucleated from vesicles obtained from bile of control patients as rapidly (2.4 days ± 0.7) as from patients with stones (2.4 days ± 0.9) and there was no difference in the vesicular cholesterol/phospholipid ratio. The effect of alteration of the bile salt environment was studied by changing the concentration of sodium cholate in the eluting buffer. At low concentrations (5 mM) only vesicles were eluted from the column. These vesicles had a relatively low cholesterol/phospholipid ratio and cholesterol nucleated slowly from these vesicles. At higher concentrations the proportion of micelles increased. The proportion of vesicles decreased progressively but their cholesterol/phospholipid ratio increased and the nucleation time fell. These studies demonstrate that cholesterol nucleates from vesicles in the absence of micelles, that control vesicles are not protected by tightly bound antinucleating substances and that exposure of vesicles to micelles strips relatively more phospholipid than cholesterol from the vesicular fraction, resulting in vesicles with higher cholesterol/phospholipid ratios and shorter nucleation times.
KW - (Human)
KW - Bile
KW - Cholesterol nucleation
KW - Gallstone
KW - Phospholipid vesicle
UR - http://www.scopus.com/inward/record.url?scp=0023633064&partnerID=8YFLogxK
U2 - 10.1016/0005-2760(87)90019-1
DO - 10.1016/0005-2760(87)90019-1
M3 - Article
C2 - 3651484
AN - SCOPUS:0023633064
SN - 0005-2760
VL - 921
SP - 198
EP - 204
JO - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
JF - Biochimica et Biophysica Acta - Lipids and Lipid Metabolism
IS - 2
ER -