HDL is the major carrier in reverse cholesterol transport (RCT). Low plasma HDL and cardiovascular disease are strongly associated. Management of dysregulated HDL metabolism and low HDL is a public health priority for which current therapies are inadequate. Thus, it is important to develop new therapies that enhance RCT. SOF, a protein from S pyogenes, clouds serum, an effect that is specific to HDL and involves liberation of lipid-free apolipoprotein A-I, formation of a cholesterol poor neo HDL, and transfer of cholesterol esters of ~100,000 HDL to a new cholesteryl ester-rich microemulsion (CERM). The CERM contains a ligand for the hepatic receptor, which allows it to be removed from the blood. The dynamics of this nonenzymatic reaction, from size exclusion chromatography, are shown here. The free energy of activation for this reaction equals the free energy of activation for the guanidinium chloride/HDL reaction, indicating that the rate limiting step is the removal of apo A-1 from HDL.
Katie Ward, ’08 Greenwood Village, CO
Major: Biochemistry and Molecular Biology
Sponsor: Craig Tepper