Liver fatty Acid-Binding Protein

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Tissue distribution and function of LFABP. Liver fatty acid-binding protein (LFABP) belongs to the mammalian family of structurally related small cytosolic lipid binding proteins. LFABP is expressed in high concentrations in hepatocytes and co-expressed with intestinal fatty acid binding protein (IFABP), ileal lipid binding protein (ILBP), and cellular retinol binding protein II (CRBP II) in the small intestine, suggesting a functional specificity for different family members [1]. Fatty acid binding proteins (FABPs) are presumably involved in the uptake and targeting of long-chain fatty acids (LCFA) and in some cases other hydrophobic ligands, to intracellular organelles and metabolic pathways although their physiological functions are as yet unclear.

Specific properties of LFABP. LFABP has particular characteristics within the FABP family which further support its unique functionality. This protein contains at least two fatty acid (FA) binding sites [2], while the other members have a single binding site for long-chain FA (LCFA) [3]; it binds a wide range of endogenous hydrophobic ligands besides LCFAs, among them acyl-CoAs [4] and lysophosphatidylcholine [5]. Besides these unique binding specificities, LFABP is distinguished from other family members by its diffusion-mediated mechanism of fatty acid transport under physiological ionic strength [6], which contrasts with the protein–membrane collisional process typical of IFABP as well as most of the other members of the FABP family of proteins [7].

LFABP structure. FABPs share a common tertiary structure consisting of ten antiparallel β-strands that form a β-barrel, which is capped by two short α-helixes arranged as a helix-turn-helix segment. It has been proposed that this helical region is part of a “dynamic portal” that regulates fatty acid entry and exit from the internal cavity [8]. In solution one ligand is found to adopt a well-defined U shape which positions its long hydrophobic chain and ionized carboxylate deep within the cavity, whereas the other ligand has a more variable extended structure with its carboxylate group close to the surface.


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