Although kinetic analysis has contributed many advances to the field of plasma lipoprotein metabolism, it has been applied at the level of whole animal or whole human physiology almost exclusively. With the advent of modern biochemical and cell culture techniques it has become feasible to employ kinetic modeling methods in the study of intracellular and organellar processes. This project is designed to test current theories concerning hepatic assembly and secretion of very low density lipoproteins (VLDL) and, where necessary, to propose and test modifications of these theories. We will employ estrogenized chick hepatocytes in short-term monolayer culture and a newly developed (hepatocyte-derived) cell-free system as our experimental model systems; kinetic data from both published and planned experiments using glycerolipid, cholesterol, apoprotein and oligosaccharide tracers will permit detailed quantitative tests of current paradigms. This testing will be done by expressing a proposed theory as a kinetic model and comparing its predictions to our experimental data using the SAAM and CONSAM computer programs. Finally, intracellular metabolite fluxes and compartmental contents will be calculated based on the tracer data and associated mass measurements.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035487-03
Application #
3349412
Study Section
Metabolism Study Section (MET)
Project Start
1985-12-01
Project End
1988-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218