Fatty Acid Binding Proteins: Considerable Progress—More Ground to Cover

Our description of the cytosolic binding activity and subsequent isolation and characterization of a specific intestinal fatty acid bindingproteus (FABP) have largely withstood the test of time and have generated new questions. One of my coauihors, Joan A. Manning, remains a memberof the research teem; her excellent contributions have played a major role in iii subsequent accomplishments. Although our early studies confirmed the hypothesis that prompted them, as welles the immediately ensuing prediction that FABP would also befound in other tissues exhibiting substantial fatty acid trans. port or metabolism, two important facts were not evident at the time. First, the FABP in four of the tissues we examined, namely, intestine, liver, myocardium, and adipose tissue, proved to be distinct hut dosely related proteins. Second, the abundance of FABP in the enterocyte reflects nearly equal expression of the liver and intestinal forms (L-FABP and l-FABP). The significance of this prominent expression of two distinct and independently reguheed FABPs in onecell remainsunknown. It has also become evident that the FABPs are members of a multigene family that includes the myelin P2 protein, the cytosolic retinol and retinoic acid binding proteins, mammary-derived growth inhibiton~,and gastrotrupin, a constituent of ileal cytosol.’ The paper’s relatively frequent citation probably reflects the fact that it, along with a nearly simultaneously published study by S. Mishkin, et aL,~pro~ vided the first evidence that, as in plasma, intracellular long-chain fatty acids are largely bound to specific soluble proteins. Our original hypothesis, that this interaction would participate in intracellular transport and metabolism of long-chain fatty acids, may prove to be correct, but no function of the FABP has been condusivelyestablished, despite the efforts ofa growing number of laboratoriesover nearly 20 years. Moreover, evidence that FABPexpression may increasd in response to increased tissuefatty acid flux rather than, as a precondition su~ests,along with other evidence, a possibly cytoprotective role.’ 3