This project is directed towards the general problem of intracellular movement of lipids. The focus is on understanding the regulation of fatty acid movement and metabolism in cardiac tissue, and to determine how this regulation is altered in conditions known to affect cardiac performance. The specific emphasis is on the potential role of fatty acid binding protein (FABP) in influencing fatty acid metabolism in the heart.
The specific aims are: 1) To-study the nature and specificity of the ligand binding sites on rat heart FABP. Binding assays, NMR, and chemical modification will be employed to correlate changes in binding with structural changes. 2) To determine if FABP functions in intracellular binding and transport of fatty acid, acyl CoA and acylcarnitine. In vitro systems containing organelles with enzymes utilizing those substances will be developed. 3) To determine if heart or liver FABP interacts with specific sites on model membrane systems or biological membranes. Iodinated FABP will be used to test for binding to isolated cellular membranes or synthetic vesicle preparations. 4) To determine if changes in amount or distribution of rat heart FABP are due to transcriptional or post- transcriptional control. 5) To use cultured neonatal cells or cell suspensions from adult myocytes for studies on factors regulating FABP turnover. It is hoped that by understanding how rat heart FABP functions in the normal regulation of cardiac lipid metabolism, the possibility that alterations in normal function may be a causative factor in certain disease states can be examined.
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