Human apolipoprotein A-IV is a newly described plasma glycoprotein of intestinal origin, with several distinct and unusual properties. Although its metabolic function is unknown at present, preliminary studies indicate that it may play an important role in the intestinal absorption of lipids and the intravascular interaction of trigly-ceride-rich particles and HDL. It is the purpose of this work to examine the structural characteristics and in vitro lipid binding properties of human apo A-IV to gain insight into its biologic behavior. The structure and conformation of apo A-IV will be examined by fluorescence and CD spectropscopy under a variety of experimental conditions. The lipid associating properties of apo A-IV will be studied in vitro using well characterized particles of a phospholipid-triglyceride emulsion (TRP) as model chylomicrons. Factors which influence the affinity of apo A-IV for these particles will be determined. The influence of other purified plasma apoproteins on the interaction of apo A-IV and TRP will be examined to investigate the mechanism by which apo A-IV is displaced from the surface of these particles. Finally, the factors influencing the affinity of apo A-IV for human HDL will be examined in vitro, with regard for the increased affinity of apo A-IV for the abnormal lipoproteins found in certain human diseases. The significance of these proposed studies is that they will develop new knowledge of the structural and biophysical properties of this poorly studied apoprotein. The long range goal of this investigation is the elucidation of the role of intestinal apoproteins in the modulation of lipoprotein metabolism, and in the process of artherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL030897-08
Application #
3341897
Study Section
Metabolism Study Section (MET)
Project Start
1990-08-01
Project End
1992-05-31
Budget Start
1990-08-01
Budget End
1991-05-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
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