Liver fatty acid-binding protein binds monoacylglycerol in vitro and in mouse liver cytosol

William S. Lagakos, Xudong Guan, Shiu Ying Ho, Luciana Rodriguez Sawicki, Betina Corsico, Sarala Kodukula, Kaeko Murota, Ruth E. Stark, Judith Storch

Research output: Contribution to journalArticle

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 NMRspectroscopy 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.

Original languageEnglish (US)
Pages (from-to)19805-19815
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number27
DOIs
StatePublished - Jul 5 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Lagakos, W. S., Guan, X., Ho, S. Y., Sawicki, L. R., Corsico, B., Kodukula, S., Murota, K., Stark, R. E., & Storch, J. (2013). Liver fatty acid-binding protein binds monoacylglycerol in vitro and in mouse liver cytosol. Journal of Biological Chemistry, 288(27), 19805-19815. https://doi.org/10.1074/jbc.M113.473579