N-Acylethanolamines are fatty acid derivatives that are amide-linked to an ethanolamine moiety. They have been shown to have potent biological activities in the plant and animal kingdoms, but much of what is known about them pertains to their regulation of animal physiology and behavior.
|Fig. 1. Molecular structure of three NAEs. *Specific N-acylethanolamine types are identified by numerical designation of their acyl chain with number of carbons: number of double bonds.
N-Acylethanolamines, or NAEs,* are fatty acid derivatives that are amide-linked to an ethanolamine moiety (Fig. 1). They differ in their acyl chain length and number of double bonds, and they are present at trace concentrations in organisms throughout the eukaryotic domain. These lipids have been shown to have potent biological activities in the plant and animal kingdoms, but much of what is known about them pertains to their regulation of animal physiology and behavior.
Several NAE types act in the endocannabinoid signaling system of vertebrates by serving as endogenous ligands to the cannabinoid receptors (CB1 and CB2). Additional studies have shown that the complement of NAEs present in animal tissues, including those that are inactive as CB receptors, act either as entourage lipids or directly on targets other than CB receptors, such as vanilloid receptor ion channels and peroxisome proliferator activated receptor transcription factors (1). Regardless of NAE type, the bioactivity in mammalian systems appears to be terminated mostly through hydrolysis via fatty acid amide hydrolase, or FAAH (2).
The prevalence of NAEs in plant systems, particularly in seeds, has been recognized for many years. More recently it has become apparent that these NAEs are metabolized by a pathway analogous to that found in animal species. Furthermore, certain NAE types are known to have potent biological activities in plant cells at micromolar concentrations, prompting speculation that an NAE lipid mediator pathway may influence growth processes and stress responses in plants (3).
Several years ago, a functional homologue of rat FAAH was identified in Arabidopsis and other plant species (4). Biochemical and molecular characterization of this enzyme from plants confirmed that it hydrolyzes NAEs, which supports the hypothesis that NAE lipid mediators and their metabolism by FAAH facilitate plant growth regulation (5), interaction with phytohormone signaling (6) and responses of plants to pathogens (7).
While NAEs may not necessarily act in plants as ligands for G-protein coupled receptors like some do in animal systems, the evolutionary conservation of the occurrence of these lipid mediators and their metabolic machinery is striking (4). Furthermore, it is the arachidonic acid-containing NAE (anandamide), or NAE20:4 (Fig. 1), that functions as the endogenous NAE ligand for the CB receptors in neuronal and peripheral signaling, whereas the CB receptor inactive NAEs in animals seem to act through other means and overlap with the most abundant NAEs in eukaryotes in general (1). In other words, NAE metabolism itself may be more central (ancient) in eukaryotic biology, and the evolution of the endocannabinoid signaling system in vertebrates may have capitalized on this pathway and paralleled the development of arachidonic acid-based signaling and the expansion of sensory perception.