Identification of N-acylethanolamines in Dictyostelium discoideum and confirmation of their hydrolysis by fatty acid amide hydrolase

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DOIResolve DOI: http://doi.org/10.1194/jlr.M032219
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TypeArticle
Journal titleJournal of Lipid Research
ISSN0022-2275
Volume54
Issue2
Pages457466; # of pages: 10
Subjectethanolamine; fatty acid amidase; fatty acid amidase inhibitor; n acylethanolamine; recombinant enzyme; unclassified drug; article; controlled study; Dictyostelium discoideum; enzyme activity; enzyme inhibition; hydrolysis; in vitro study; in vivo study; lipid analysis; nonhuman; nucleotide sequence; phylogenetic tree; priority journal; signal transduction; Amidohydrolases; Animals; Computational Biology; Dictyostelium; Enzyme Inhibitors; Ethanolamines; Humans; Hydrolysis; Kinetics; Mice; Phylogeny
AbstractN-acylethanolamines (NAEs) are endogenous lipid-based signaling molecules best known for their role in the endocannabinoid system in mammals, but they are also known to play roles in signaling pathways in plants. The regulation of NAEs in vivo is partly accomplished by the enzyme fatty acid amide hydrolase (FAAH), which hydrolyses NAEs to ethanolamine and their corresponding fatty acid. Inhibition of FAAH has been shown to increase the levels of NAEs in vivo and to produce desirable phenotypes. This has led to the development of pharmaceutical-based therapies for a variety of conditions targeting FAAH. Recently, our group identified a functional FAAH homolog in Dictyostelium discoideum, leading to our hypothesis that D. discoideum also possesses NAEs. In this study, we provide a further characterization of FAAH and identify NAEs in D. discoideum for the first time. We also demonstrate the ability to modulate their levels in vivo through the use of a semispecific FAAH inhibitor and confirm that these NAEs are FAAH substrates through in vitro studies. We believe the demonstration of the in vivo modulation of NAE levels suggests that D. discoideum could be a good simple model organism in which to study NAE-mediated signaling. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Human Health Therapeutics (HHT-TSH)
Peer reviewedYes
NPARC number21269675
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Record identifier42653b13-2984-41c9-9a0a-28f087626843
Record created2013-12-13
Record modified2016-05-09
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