Zheng, Hui2013-11-072013-11-0720052005Source: Masters Abstracts International, Volume: 44-04, page: 1844.http://hdl.handle.net/10393/27101http://dx.doi.org/10.20381/ruor-11917The liver is the site for both apolipoprotein A-I (apoA-I) synthesis and ATP-binding cassette transporter A1 (ABCA1) expression. To investigate the function of hepatic lipidation of apoA-I by cholesterol and phospholipid, and delineate the role of hepatic ABCA1 in these lipidation pathways, I have expressed human apoA-I by adenovector-mediated gene transfer into primary mouse hepatocytes. Kinetic studies demonstrate that newly synthesized apoA-I acquires both cholesterol and phospholipid during secretion and at the cell surface. Approximately 80% of the phospholipidation, and only 40--60% of the cholesterol lipidation of apoA-I is ABCA1-dependent. Hepatic apoA-I cholesterol lipidation depends on the active transfer from intracellular compartments to the cell surface. Under ABCA1 deficiency, both apoA-I and cholesterol associated with apoA-I in high-density lipoprotein (HDL) fraction decrease, but the nature of the lipoprotein particles is not affected. Furthermore, this study demonstrates the different regulation and/or controls are required for apoA-I cholesterol lipidation and phospholipidation.125 p.enChemistry, Biochemistry.Thesis