The human fatty acid-binding protein family: Evolutionary divergences and functions

Hydrophobic ligands, such as fatty acids (FAs) and their acyl-CoA derivatives (FA-CoA), serve many biological functions within the cell. They serve as metabolic energy sources, substrates for membranes and signalling molecules for metabolic regulation [1,2]. The insoluble properties of FAs make for the requirement for chaperones to bind and transfer them throughout various cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum, lipid droplets and nucleus. A family of highly expressed intracellular lipid-binding proteins (iLBPs)--the fatty acid-binding proteins (FABPs)--serves to bind these free ligands with high affinity. FABPs are ubiquitously expressed throughout tissues that are highly active in FA metabolism and comprise several isoforms. To date, nine FABP protein-coding genes have been identified in the human genome. These include liver(L-FABP), intestine- (I-FABP), heart- (H-FABP), adipocyte- (A-FABP), epidermal- (E-FABP), ileal-(Il-FABP), brain- (B-FABP), myelin- (M-FABP) and testis-FABP (T-FABP). These different isoforms were first named for the organ in which they were first identified or mostly predominate, but their expression profiles are not exclusive to that specific organ. For example, L-FABP is not only expressed in the liver, but also in the intestine, pancreas, kidney, lung and stomach. In addition to the nine known FABPs that have been widely studied, a newer member of the family, FABP12, has recently been discovered. The gene has been identified, but published reports on the protein encoded by this gene are not yet available. Therefore, in this reviews only the identification of the gene will be addressed.Although members of the FABP family share moderate sequence homologies of 20-70 per cent, their tertiary structures are virtually superimposable [3-5]. Sequences of human FABPs are aligned in Figure 1. These ~15-kilodalton proteins comprise ten anti-parallel β-barrel (βA-βJ) structures containing a solvent-accessi