Fatty acid binding proteins (FABPs) comprise a family of abundant, low molecular weight cytosolic proteins found in heart, liver, intestine and other organs. It has been assumed that FABPs function in the intracellular transport of long chain fatty acids and their metabolites. Heart FABPs would be expected to have a particularly important function because fatty acids are a major fuel source for cardiac muscle and because accumulation of amphipathic molecules, such as fatty acids, is believed to cause membrane damage following ischemic injury. The overall goal of this proposal is to understand the role of FABP in human heart. Human heart FABP, which has recently been purified in this laboratory, will be characterized and the complete amino acid sequence determined. FABP from human skeletal muscle will also be purified and its structural relationship to human heart FABP elucidated. Functional studies on both human heart and skeletal muscle FABP will be performed by determining the fatty acid binding characteristics toward five physiologically abundant long chain fatty acids. Binding studies will also be performed on covalently modified proteins to gain insights into the structural features of the fatty acid binding site. Antibodies directed against rat heart FABP have been produced and will be used in an enzyme linked immunosorbant assay to measure FABP levels in normal and ischemic rat heart as well as to determine if FABP levels display a diurnal variation. These studies will be complemented by the use of a cDNA probe for rat heart FABP that will be used to measure FABP mRNA levels in normal and ischemic rat hearts. Antibodies to human heart FABP have also been prepared and have been used to develop an enzyme linked immunosorbant assay for this protein. This assay will be used to measure FABP in serum of patients admitted to the Boston City Hospital Coronary Care Unit to determine if serum levels of FABP can be a useful index of myocardial damage.
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