FATP

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Several different proteins have been shown to facilitate transport of long-chain fatty acids have been characterised in different species at the protein and/or gene levels (Tab.1). These include the long-chain fatty acid transporter protein family, with six different FATP, designated FATP1 to 6, identified in humans (Hirsch et al. 1998), the fatty acid translocase (FAT) (Abumrad et al. 1993), and the membrane-associated plasmalemmal fatty acid-binding protein (FABPpm) (Stremmel et al. 1985). Co-expression of genes coding for FATP, FAT and FABPpm in rat heart and muscle cells (Van Nieuwenhoven et al. 1999), and human skeletal muscle (Bonen et al. 1999) suggests that the uptake processes may involve the co-operation of a number of proteins. Fatty acids are converted to their respective acyl-CoA esters by different fatty acyl-CoA synthetases. The imported long-chain fatty acids are esterified by long-chain acyl-CoA synthetase (LACS) located at the outer leaflet of the plasma membrane in adipocytes (Gargiulo et al. 1999), the outer mitochondrial membrane of skeletal muscle and microsomes in the liver, whereas the short- and medium-chain fatty acids are activated within the mitochondrial matrix (Trevisan et al. 1995). Following their uptake, the fatty acids and derivatives translocate through the aqueous cytoplasm to the mitochondria, possibly with the aid of cytoplasmic fatty acid-binding proteins (FABPc) (Glatz et al. 1998). FABPs belong to the conserved multigene family of the intracellular lipid binding proteins (iLBPs). These proteins are ubiquitously expressed in vertebrate tissues, with distinct expression patterns for the individual FABPs. Various functions have been proposed for these proteins, including the promotion of cellular uptake and transport of fatty acids, the targeting of fatty acids to specific metabolic pathways, and the participation in the regulation of gene expression and cell growth. Transgenic cell lines, animals, and knockout mice have helped to define essential cellular functions of individual FABP-types or of combinations of several different FABPs. The deletion of particular FABP genes, however, has not led to gross phenotypical changes, most likely because of compensatory overexpression of other members of the iLBP gene family, or even of unrelated fatty acid transport proteins. In recent years, a numerical nomenclature for the various FABP genes has been introduced (Haunerland and Spener, 2004; Hertzel and Bernlohr, 2000), but the various FABPs are still named after the tissues in which they have been discovered, or are prominently expressed (Tab.2). It should be recognized, however, that such a classification is somewhat misleading, since no FABP is specific for a given tissue, and most tissues express various FABP-types.
L-FABP, for example, is strongly expressed in the liver, and was thought to be the only FABP expressed in this tissue, at least in adult animals (recent studies have reported the presence of E-FABP, I-FABP, and A-FABP in liver as well [13,14]). But L-FABP is also found, albeit in far smaller concentrations, in the intestine, kidney, lung, and pancreas. In contrast, I-FABP and I-BABP are confined to the digestive tract and not expressed prominently in other tissues (Chmurzynska 2006). H-FABP and E-FABP are the most ubiquitously expressed iLBPs; the former is most prominent in cardiac and skeletal muscle, but also present in kidney, lung, mammary tissue, placenta, testis, stomach, ovary, and the brain. The latter protein is widely expressed in skin, lung, heart and skeletal muscle, kidney, testis, and adipose tissue, as well as in the brain and the retina. In addition to H- and E-FABP, the nervous system contains two other FABPs, B-FABP that is present in brain and retina, and the M-FABP that seems to be specific for the Schwann cells forming the myelin sheath. A-FABP was originally thought to be confined to adipocytes, but has been detected in macrophages as well.

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