Fatty acid-binding protein

About: Fatty acid-binding protein is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 81530 citations. The topic is also known as: FABP.

The binding of cholesterol and bile salts to recombinant rat liver fatty acid-binding protein

Abstract: The physiological role of liver fatty acid-binding protein (L-FABP) has yet to be clarified. An important feature of this member of the family of intracellular lipid-binding proteins is the wide range of compounds that have been identified as potential physiological ligands. By using recombinant L-FABP, the binding of cholesterol, bile salts and their derivatives has been investigated under conditions that allow a direct comparison of the binding affinities of these ligands for fatty acids. The results demonstrate an inability of L-FABP to bind cholesterol, although the anionic derivative, cholesteryl sulphate, will bind under similar assay conditions. Of the bile salts examined, lithocholate and taurolithocholate sulphate showed the greatest binding to L-FABP. It is proposed that an important function of L-FABP is to bind certain physiological amphipathic anions, thus preventing the "free' concentrations of these compounds from exceeding their critical micelle concentration, which could result in cell damage.

Liver fatty acid-binding protein as a sensitive serum marker of acute hepatocellular damage in liver transplant recipients.

Abstract: Serum tests of acute hepatocellular injury are commonly used to investigate the presence and monitor the progress of liver disease (1)(2). The release of cytoplasmic proteins from damaged hepatocytes into the vascular system follows tissue necrosis caused by, e.g., acetaminophen intoxication, ischemia and reperfusion injury, or rejection after liver transplantation. Although the hepatocytes are in direct contact with the vasculature and no interstitial barrier is between the two, smaller proteins appear earlier in the circulation than do larger ones (1) and would therefore increase earlier in serum above their upper reference value after an acute hepatocellular injury. α-Glutathione S -transferase (α-GST; 26 kDa) is a more sensitive and specific marker of hepatocellular damage (3)(4) than either alanine transaminase (ALT; 96 kDa) or aspartate transaminase. α-GST is present in liver, kidney, and intestine; is released rapidly from damaged hepatocytes; and has a relatively short in vivo plasma half-life (3)(4). The use of α-GST for the detection of hepatocellular injury secondary to acute rejection after liver transplantation improved the biochemical monitoring of patients and decreased mortality and morbidity (3). In search of even smaller and more specific cytoplasmic proteins for the detection of liver injury, we have studied the liver-type fatty acid-binding protein (L-FABP). FABPs are a family of 15-kDa proteins that are involved in the intracellular transport of long-chain fatty acids (5). To date, nine different FABPs have been identified and named according to the tissues in which they were first identified (5). L-FABP occurs mainly in the liver but, in small quantities, also in kidney and small intestine. In the hepatic lobule, L-FABP is expressed in hepatocytes in a declining portal-to-central gradient (5)(6). Extensive studies …

Cellular differentiation and I-FABP protein expression modulate fatty acid uptake and diffusion

Abstract: The effect of cellular differentiation on fatty acid uptake and intracellular diffusion was examined in transfected pluripotent mouse embryonic stem (ES) cells stably expressing intestinal fatty ac...

Historic overview of studies on fatty acid-binding proteins

Abstract: Fatty acid-binding proteins (FABPs) were first identified in the cytosol of rat intestinal mucosa during studies on the regulation of intestinal fatty acid uptake. The subsequent finding of FABP activity in the cytosol of many other tissues initially was believed to reflect a single protein. However, the FABPs are now recognized as products of an ancient gene family comprised of at least 9 structurally related, soluble intracellular members, a number of which exhibit high-affinity binding of long-chain fatty acids. Despite recent insights into regulation and tissue-specific expression suggesting FABPs to subserve diverse roles, their precise biological functions remain to be elucidated.

Cellular binding proteins for fatty acids and retinoids: similar or specialized functions?

Abstract: The cellular fatty acid-binding proteins (FABP) and cellular retinoid (retinol, retinoic acid)-binding proteins (CRtBP) are structurally and functionally-defined groups within an evolutionarily conserved gene family. CRtBP are expressed in both fully differentiated and developing tissues in a manner that supports a relationship to the action of retinoic acid in morphogenesis and cellular differentiation. The FABP are, by contrast, expressed only in fully differentiated tissues in a manner compatible with a major function in the metabolism of long-chain fatty acids (LCFA) for energy production or storage. The precise function(s) of FABP and CRtBP remain imperfectly understood, while subspecialization of function(s) within the two groups is suggested by the complex diversity in both of structurally distinct members that display striking tissue and temporal specificity of expression in addition to ligand specificity. Notwithstanding this considerable apparent functional diversity among the FABP and CRtBP, available evidence supports a dual set of generic functions for both protein groups in a) promoting cellular flux of poorly water-soluble ligands and their subsequent metabolic utilization or transformation, and b) sequestration of ligands in a manner that limits their association with alternative binding sites within the cell, of which members of the steroid hormone nuclear receptor superfamily (HNR) are a potentially important category. Theoretical as well as experimental models probing diffusional fluxes of LCFAin vitro and in living cells have provided support for a function for FABP in intracellular LCFA transport. Protein-bound ligand also appears to provide the substrate for metabolic transformation of retinoids bound to CRtBP, but convincing evidence is lacking for an analogous mechanism in the direct facilitation of fatty acid utilization by FABP. An emerging relationship between FABP and CRtBP function centers on their binding of, and induction by, ligands which activate or transform specific HNR-the retinoic acid receptors and the peroxisome proliferator activated receptor in the case of CRtBP and FABP, respectively. Evidence consistent with both a ‘promotive’ role (provision of ligands for HNR) and a ‘protective’ role (limiting availability of free ligand for HNR association) has been advanced for CRtBP. Available data supports a ‘protective’ function for cellular retinoic acid-binding proteins (CRABP) and liver FABP (L-FABP) and points to the existence of ligand-defined, lipid-binding-protein-HNR relationships in which CRABP serve to attenuate the induction of gene expression by retinoic acid, and in which L-FABP may modulate a cellular adaptive multigene response to increased LCFA flux or compromised LCFA utilization. Furthermore, the emerging role of LCFA in the regulation of gene expression combined with the complex interplay between heterologous HNR-ligand associations and gene cross-regulation implies an important potential interaction between FABP, CRtBP, and their respective ligands in gene regulation.