The plasma lipoproteins (LPs) transport lipids between various extravascular compartments where they are utilized or stored. The high density LPs (HDL), very low density LPs (VLDL), and chylomicrons are modified in plasma by two enzymes. The free cholesterol of HDL is converted to its esterified form by lecithin:cholesterol acyltransferase (LCAT), an enzyme that also has phospholipase A2 activity; both processes are activated by apoA-I. Lipoprotein lipase (LPL) hydrolyzes the triglycerides of VLDL and chylomicrons, a reaction that is timulated by apoC-II. These enzymes are important in determining the distribution of steryl or fatty acyl groups among individual lipids and the distribution of these lipids among the plasma LPs. A molecular description of the activities and specificities of both enzymes is a key component of a thorough understanding of lipid metabolism since these activities determine the product structure, which affects their distribution inplasma. We propose a) to resolve the specificities of these enzymes into components that are dependent either upon the covalent structure of the individual substrate molecules or upon macroscopic properties such as fluidity or size, b) to measure the free energy of association (Delta Ga) of LCAT and LPL with phospholipids in the presence and absence of their apoprotein activators, and c) to determine the relationship between Delta Ga and the structure of the substrate and product LPs. These studies will be conducted with ether analogs of lipids, and a variety of hydrolyzable fluorescent or radioactive lipids. This investigation involves lipid synthesis, fluorescence and radioactive assays of LPL and LCAT activity, lipoprotein reassembly, and equilibrium binding techniques. The initial studies will utilize single bilayer vesicles and then progress to well-characterized model and native LPs. Since lifestyles determine, in part, the fatty acid composition of lipids, and the quantity and structure of the LPs that contain them, our studies should aid in our understanding of the factors that affect plasma LP turnover and lipid metabolism in general.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Rosales, C; Davidson, W S; Gillard, B K et al. (2016) Speciated High-Density Lipoprotein Biogenesis and Functionality. Curr Atheroscler Rep 18:25
Rodriguez, Perla J; Gillard, Baiba K; Barosh, Rachel et al. (2016) Neo High-Density Lipoprotein Produced by the Streptococcal Serum Opacity Factor Activity against Human High-Density Lipoproteins Is Hepatically Removed via Dual Mechanisms. Biochemistry 55:5845-5853
Pownall, Henry J; Gotto Jr, Antonio M (2016) New Insights into the High-Density Lipoprotein Dilemma. Trends Endocrinol Metab 27:44-53
Pownall, Henry J; Schwartz, Anne V; Bray, George A et al. (2016) Changes in regional body composition over 8 years in a randomized lifestyle trial: The look AHEAD study. Obesity (Silver Spring) 24:1899-905
Rosales, Corina; Patel, Niket; Gillard, Baiba K et al. (2015) Apolipoprotein AI deficiency inhibits serum opacity factor activity against plasma high density lipoprotein via a stabilization mechanism. Biochemistry 54:2295-302
Pownall, Henry J; Bray, George A; Wagenknecht, Lynne E et al. (2015) Changes in body composition over 8 years in a randomized trial of a lifestyle intervention: the look AHEAD study. Obesity (Silver Spring) 23:565-72
Pownall, Henry J; Gillard, Baiba K; Gotto Jr, Antonio M (2013) Setting the course for apoAII: a port in sight? Clin Lipidol 8:551-560
Vasudevan, Madhuri; Tchoua, Urbain; Gillard, Baiba K et al. (2013) Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome. J Clin Lipidol 7:661-70
Gillard, Baiba K; Raya, Joe L; Ruiz-Esponda, Raul et al. (2013) Impaired lipoprotein processing in HIV patients on antiretroviral therapy: aberrant high-density lipoprotein lipids, stability, and function. Arterioscler Thromb Vasc Biol 33:1714-21
Wooten, Joshua S; Nambi, Preethi; Gillard, Baiba K et al. (2013) Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients. Med Sci Sports Exerc 45:1043-50

Showing the most recent 10 out of 96 publications