title: Effects of synthetic alkamides on Arabidopsis fatty acid amide hydrolase activity and plant development.
abstract: Alkamides and N-acylethanolamines (NAEs) are bioactive, amide-linked lipids that influence plant development. Alkamides are restricted to several families of higher plants and some fungi, whereas NAEs are widespread signaling molecules in both plants and animals. Fatty acid amide hydrolase (FAAH) has been described as a key contributor to NAE hydrolysis; however, no enzyme has been associated with alkamide degradation in plants. Herein reported is synthesis of 12 compounds structurally similar to a naturally occurring alkamide (N-isobutyl-(2E,6Z,8E)decatrienamide or affinin) with different acyl compositions more similar to plant NAEs and various amino alkyl head groups. These "hybrid" synthetic alkamides were tested for activity toward recombinant Arabidopsis FAAH and for their effects on plant development (i.e., cotyledon expansion and primary root length). A substantial increase in FAAH activity was discovered toward NAEs in vitro in the presence of some of these synthetic alkamides, such as N-ethyllauroylamide (4). This "enhancement" effect was found to be due, at least in part, to relief from product inhibition of FAAH by ethanolamine, and not due to an alteration in the oligomerization state of the FAAH enzyme. For several of these alkamides, an inhibition of seedling growth was observed with greater results in FAAH knockouts and less in FAAH over-expressing plants, suggesting that these alkamides could be hydrolyzed by FAAH in planta. The tight regulation of NAE levels in vivo appears to be important for proper seedling establishment, and as such, some of these synthetic alkamides may be useful pharmacological tools to manipulate the effects of NAEs in situ.
authors.affiliation: Center for Plant Lipid Research, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA.
authors.forename: Lionel
authors.initials: L
authors.lastname: Faure
authors.affiliation: Department of Chemistry, University of North Texas, Denton, TX 76203, USA.
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Cavazos
authors.affiliation: The Samuel Roberts Noble Foundation, Plant Biology Division, Ardmore, OK 73401, USA.
authors.forename: Bibi Rafeiza
authors.initials: BR
authors.lastname: Khan
authors.affiliation: Department of Chemistry, University of North Texas, Denton, TX 76203, USA. Electronic address: Robby.Petros@unt.edu.
authors.forename: Robby A
authors.initials: RA
authors.lastname: Petros
authors.affiliation: Center for Plant Lipid Research, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA; Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri - Kansas City, Kansas City, MO, USA; Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Kansas City, MO, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.affiliation: Center for Plant Lipid Research, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA; The Samuel Roberts Noble Foundation, Plant Biology Division, Ardmore, OK 73401, USA.
authors.forename: Elison B
authors.initials: EB
authors.lastname: Blancaflor
authors.affiliation: Center for Plant Lipid Research, Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA. Electronic address: chapman@unt.edu.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Chapman
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D017360:Arabidopsis / Q000201:enzymology / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism*; D015394:Molecular Structure; D063245:Plant Development; D053284:Polyunsaturated Alkamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D036226:Seedlings / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D004983:Ethanolamines; D006867:Hydrolases; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C022203:N-acylethanolamines; C489347:N-isobutyl-2E-decenamide
keywords: Affinin; Alkamide; Arabidopsis thaliana; Fatty acid amide hydrolase; Lipids; N-Acylethanolamine