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.

Sterol carrier protein-2: not just for cholesterol any more.

Abstract: Although sterol carrier protein-2 (SCP-2) mediates cholesterol esterification in L-cell fibroblasts and stimulates an accumulation of cholesterol in these cells, a potential role for SCP-2 in fatty acid uptake and trafficking has not been appreciated. Certainly, recent experiments have shown that SCP-2 binds fatty acids in vitro with an affinity similar to that observed for fatty acid binding proteins. Because of the ubiquitous tissue distribution of SCP-2, as opposed to the specific distribution of fatty acid binding proteins, as well as the need for fatty acid trafficking in all cells, I have recently proposed that SCP-2 is the universal fatty acid trafficking protein. This supposition is based on a number of observations made with L-cell fibroblasts expressing either the 13.2 kDa SCP-2 or the 15 kDa proSCP-2. In L-cells expressing the 13.2 kDa SCP-2, fluorescent fatty acid uptake was increased by 10–30% depending upon the probe used. In 15 kDa proSCP-2 expressing cells, fluorescent fatty acid uptake was increased 20–40% depending upon the probe used. However, only expression of the 15 kDa pro-SCP-2 increased the cytoplasmic diffusion of the fluorescent fatty acid. Expression of either protein increased the uptake of [3H]-oleic acid 1.9-fold compared to control, with targeting of [3H]-oleic acid for esterification into cholesteryl esters. The 13.2 kDa SCP-2 did target a significant amount of [3H]-oleic acid for esterification into the triacylglycerol pool. Expression of either protein markedly reduced total cellular phospholipid levels, however both proteins increased cholesteryl ester levels. Interestingly, expression of the 15 kDa proSCP-2 decreased ethanolamine plasmalogen levels with a concomitant increase in choline plasmalogen. Expression of both proteins increased PUFA content of the phospholipids, although this effect was greater in 15 kDa proSCP-2 expressing cells. Hence, expression of SCP-2 increased fatty acid uptake and targeted fatty acid to unique lipid pools, suggesting that SCP-2 may effectively serve as universal fatty acid binding and trafficking protein.

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites.

Abstract: Disposition kinetics of [3H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [3H]palmita...

Fatty acid metabolism in human breast cancer cells (MCF7) transfected with heart-type fatty acid binding protein.

Abstract: The human breast cancer cell line MCF7 does not express heart-type fatty acid binding protein (H-FABP), a marker protein for differentiated mammary gland. MCF7 cells transfected with the bovine H-FABP cDNA expressed the corresponding protein and were characterized by growth inhibition and lower tumorgenicity in nude mice [22]. By enzyme linked immunoassay we now determined the amount of bovine H-FABP in these cells as 638 ± 80 ng/mg protein and used the transfected cells to study the role of H-FABP in fatty acid metabolism. Compared to control cells the uptake of radioactively labelled palmitic acid and oleic acid into MCF7 cells after 30 or 60 min was increased by 67% in H-FABP expressing transfectants, demonstrating a stimulatory role for this FABP-type in fatty acid metabolism. However, preferential targeting of [14C]oleic acid into neutral or phospholipid classes was not observed by the criterion of high performance thin layer chromatography followed by autoradiography. A reason for the modest increase of fatty acid uptake in H-FABP transfected MCF7 cells may be the basal expression of epidermal-type FABP, which was detected for the first time in these cells. It appears that the small amount of E-FABP expressed in MCF7 cells fulfils the need of the cells for a cytosolic fatty acid carrier under culture conditions and that even high concentrations of another FABP do only slightly increase the uptake due to limitations of fatty acid transport through the plasma membrane or of metabolism.

Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

Abstract: Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.