FATTY-ACID-BINDING PROTEIN ISOFORMS - STRUCTURE AND FUNCTION

Although structural aspects of cytosolic fatty acid binding proteins ( FABPs) in mammalian tissues are now well understood, significant advan ces regarding the physiological function(s) of these proteins have bee n slow in forthcoming. Part of the difficulty lies in the complexity o f the multigene FABP family with nearly twenty identified members. Fur thermore, isoelectric focusing and ion exchange chromatography operati onally resolve many of the mammalian native FABPs into putative isofor ms. However, a more classical biochemical definition of an isoform, i. e. proteins differing by a single amino acid, suggests that the operat ional definition is too broad. Because at least one putative heart H-F ABP isoform, the mammary derived growth inhibitor, was an artifact (Sp echt et al. (1996) J. Biol. Chem. 271: 1943-49), the ensuing skepticis m and confusion cast doubt on the existence of FABP isoforms in genera l. Yet. increasing data suggest that several FABPs, e.g. human intesti nal I-FABP, bovine and mouse heart H-FABP, rabbit myelin P2 protein an d bovine liver L-FABP may exist as true isoforms. In contrast, the rat liver L-FABP putative isoforms may actually be due either to bound li gand, post-translational S-thiolation and/or structural conformers. In any case, almost nothing is known regarding possible functions of eit her the true or putative isoforms in vitro or in vivo. The objective o f, this article is to critically evaluate which FABPs form biochemical ly defined or true isoforms versus FABPs that form additional forms, o perationally defined as isoforms. In addition, recent developments in the molecular basis for FABP true isoform formation, the processes lea ding to additional operationally defined putative isoforms and insight s into potential function(s) of this unusual aspect of FABP heterogene ity will be examined. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.