Combined interaction of phospholipase C and apolipoprotein A-I with small unilamellar vesicles in the context of gallstone disease /
Combined interaction of phospholipase C and apolipoprotein A-I with small unilamellar
vesicles in the context of gallstone disease
Manasa V. Gudheti
Advisor: Steven P. Wrenn, Ph.D.
Gallstone disease is the most common gastrointestinal disease that afflicts 10-15%
of the US population with an annual cost of over $10.5 billion. Though the aetiolgy of
the disease is well understood, more research is warranted regarding the pathogenesis.
Knowledge about the gallstone pathway will aid in the measures for prophylactic
Gallstones form due to the precipitation of cholesterol from cholesterolsupersaturated
bile. Small unilamellar vesicles (SUVs) are the predominant transporters
of cholesterol in bile. Precipitation of cholesterol monohydrate crystals from aggregated
and/or fused SUVs in cholesterol-supersaturated bile followed by crystal accretion and
growth leads to gallstone formation. The rate at which cholesterol nucleates from the
vesicles, which is influenced by a host of biliary factors, plays a pivotal role in
determining the lithogenicity of bile. The kinetic factors are divided into pro-nucleating
and anti-nucleating factors that enhance and inhibit nucleation respectively. The balance
between the two factors is largely responsible for the incidence of gallstones.
This research focuses on understanding the concerted influence of phospholipase
C (PLC), a pro-nucleating enzyme, and apolipoprotein (apo A-I), an anti-nucleating
protein, on small unilamellar vesicles. We find that apo A-I exerts its anti-nucleating
protection via two mechanisms, anti-aggregation and complex formation. The mode of
protection is dependent on the vesicle composition, and PLC and apo A-I concentrations.
It has been previously speculated that apo A-I/lipid complexes exist in bile and
this research effort provides proof and confirms prior allusions. The similarities in
physical chemistry between gallstone disease and atherosclerosis enable this research to
be applied in the study of coronary heart disease.
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Keywords:chemical engineering gastrointestinal system gallstones
Date of Publication: