title: Liver fatty acid-binding protein binds monoacylglycerol in vitro and in mouse liver cytosol.
abstract: Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803-G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP(-/-) mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG.
authors: Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA.
authors: William S
authors: WS
authors: Lagakos
authors: Xudong
authors: X
authors: Guan
authors: Shiu-Ying
authors: SY
authors: Ho
authors: Luciana Rodriguez
authors: LR
authors: Sawicki
authors: Betina
authors: B
authors: Corsico
authors: Sarala
authors: S
authors: Kodukula
authors: Kaeko
authors: K
authors: Murota
authors: Ruth E
authors: RE
authors: Stark
authors: Judith
authors: J
authors: Storch
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050178:Monoglycerides / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D051381:Rats
chemical_list: C493320:Fabp1 protein, mouse; C493321:Fabp1 protein, rat; D050556:Fatty Acid-Binding Proteins; D050178:Monoglycerides
keywords: Fatty Acid-binding Protein; Fatty acid; Lipid Transport; Monoacylglycerol; NMR
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