N-Acylethanolamine
An N-acylethanolamine (NAE) is a type of fatty acid amide formed when one of several types of acyl group is linked to the nitrogen atom of ethanolamine. These amides conceptually can be formed from a fatty acid and ethanolamine with the release of a molecule of water, but the known biological synthesis uses a specific phospholipase D to cleave the phospholipid unit from N-acylphosphatidylethanolamines.[1] Another route relies on the transesterification of acyl groups from phosphatidylcholine by an N-acyltransferase (NAT) activity.[citation needed] The suffixes -amine and -amide in these names each refer to the single nitrogen atom of ethanolamine that links the compound together: it is termed "amine" in ethanolamine because it is considered as a free terminal nitrogen in that subunit, while it is termed "amide" when it is considered in association with the adjacent carbonyl group of the acyl subunit. Names for these compounds may be encountered with either "amide" or "amine" varying by author.[2]
Examples of N-acylethanolamines include:[3]
- Anandamide (N-arachidonoylethanolamine; NAE) or arachidonoylethanolamine (AEA: C22H37NO2; 20:4, ω-6) is the amide of arachidonic acid (C20H32O2; 20:4, ω-6) and ethanolamine (MEA: C2H7NO). It is the ligand of both cannabinoid receptors and vanilloid receptor that attenuates pain sensation.[4][5][6][7]
- N-Palmitoylethanolamine (PEA: C18H37NO2; 16:0) is the amide of palmitic acid (C16H32O2; 16:0) and ethanolamine. It is a ligand at CB2-like receptors.[8] It has anti-inflammatory activity and also attenuates pain sensation.[7][9][10] in mammals. NAE 16:0 has also been identified in plants including corn, and seeds of cotton, okra, tomato, castor bean, soya bean and peanuts,[11] but its physiological functions remain unknown,[12]
- N-Oleoylethanolamine (OEA: C20H39NO2; 18:1,ω-9) is the amide of oleic acid (C18H34O2; 18:1) and ethanolamine. It has anorexic effects and enables fat breakdown by stimulating PPAR-alpha.[13] In plants NAE 18:1 is present abundantly in dry seeds and levels decline during seed imbibition,[11][14] but its physiological functions are yet to be elucidated. In humans, plasma OEA levels are also found positively correlated with positive mood and emotions.[15]
- N-Stearoylethanolamine (C20H41NO2; 18:0) is the amide of stearic acid (C18H36O2) and ethanolamine. It has pro-apoptotic activity. It operates independently of the known cannabinoid and vanilloid receptors targeted by anandamide.[13] It is an inhibitor of the sphingolipid signaling pathway, via specific ceramidase inhibition (ceramidase converts ceramide to sphingosine) and blocks the effects of TNF- and arachidonic acid on intracellular Ca2+ concentration.[16][17][18]
- N-Docosahexaenoylethanolamine (C24H37NO2; 22:6,ω-10), "synaptamide", is the amide of docosahexaenoic acid (DHA: C22H32O2; 22:6,ω-3) and ethanolamine. It has anti-proliferative effects on prostate cancer cell lines and promotes synaptogenesis, neurogenesis and neuritogenesis,[19][20] and as an endogenous metabolite of DHA, it promotes brain development and function.[21]
- N-Docosatetraenoylethanolamine (DEA: C24H41NO2; 22:4,ω-6) act on the CB1 receptor,[8] and possible CB2.[16]
- N-homo-gamma-linolenoylethanolamine, or Anandamide (20:3,n-6) (HGLEA: C22H39NO2; 20:3,ω-6).[22]
These bioactive lipid amides are generated by the membrane enzyme NAPE-PLD, and natural bile acids regulate this essential process,[23].
All are members of the endocannabinoidome, a complex lipid signaling system composed of a plethora of more than 100 of fatty acid-derived mediators and their receptors, its anabolic and catabolic enzymes of more than 50 proteins, which also are deeply involved in the control of energy metabolism and its pathological deviations.[24]
Beyond vertebrates, NAEs are also found to have signaling roles in more primitive organisms, implicated as metabolic signals that coordinate nutrient status and lifespan determination in Caenorhabditis elegans, and detected in organisms as diverse as yeast (Saccharomyces cerevisiae), fresh water fish (Esox lucius and Cyprinus carpio), bivalve mollusc (Mytilus galloprovincialis), protists (Tetrahymena thermophila) and slime mold (Dictyostelium discoideum), organisms that appear to regulate their endogenous NAE levels via similar enzymatic machinery as mammalian vertebrates, show a widespread occurrence of NAEs, from single-celled organisms to humans, and a highly conserved role for this group of lipids in cell signaling.[25]
Mood
As the euphoric feeling described after running, called the "runners high" is, at least in part, due to increased circulating endocannabinoids (eCBs), and these lipid signaling molecules are involved in reward, appetite, mood, memory and neuroprotection, an analysis of endocannabinoid concentrations and moods after singing, dancing, exercise and reading in healthy volunteers, showed that singing increased plasma levels of anandamide (AEA) by 42%, palmitoylethanolamine (PEA) by 53% and oleoylethanolamine (OEA) by 34%, and improved positive mood and emotions. Dancing did not affect eCB levels, but decreased negative mood and emotions. Cycling increased OEA levels by 26%, and reading increased OEA levels by 28%. All the ethanolamines were positively correlated with heart rate. As so, the plasma OEA levels were positively correlated with positive mood and emotions, and AEA levels were seen positively correlated with satiation.[15]
Metabolic production of NAEs
Diets in mammals, containing 20:4,n−6 and 22:6,n−3, are found to increase several biologically active NAEs in brain homogenates as metabolic products, like 20:4,n−6 NAE (4-fold), 20:5,n−3 NAE (5-fold), and 22:5,n−3 and 22:6,n−3 NAE (9- to 10-fold). The increase in all of the metabolic NAEs is regarded biologically important, because NAEs having fatty acids with at least 20 carbons and three double bonds bind to CB1 receptors,[26] and endogenously released NAE 20:4 and 2-arachidonylglycerol (2AG: C23H38O4; 20:4,n-6) are also found to activate CB2 receptors in addition.[16]
NAEs in plants
N-acylethanolamines (NAEs) constitute a class of lipid compounds naturally present in both animal and plant membranes, as constituents of the membrane-bound phospholipid, N-acylphosphatidylethanolamine (NAPE). NAPE is composed of a third fatty acid moiety linked to the amino head group of the commonly occurring membrane phospholipid, phosphatidylethanolamine.[16]
It is found, that the levels of NAEs increases 10- to 50-fold in tobacco (Nicotiana tabacum) leaves treated with fungal elicitors, as protection, by producing the N-myristoylethanolamine (C16H33NO2; NAE 14:0), that specific binds to a protein in tobacco membranes with biochemical properties appropriate for the physiological responses, and it do not show identical binding properties to NAE-binding proteins in intact tobacco microsomes, compared to non-intact microsomes. In addition to this, an antagonists of mammalian CB receptors was seen to block both of the biological activities previously attributed to NAE 14:0, this endogenous NAE that is accumulated in tobacco cell suspensions and leaves after pathogen elicitor perception, is why it is proposed, that plants possess an NAE-signaling pathway with functional similarities to the “endocannabinoid” pathway of animal systems, and this pathway, in part, participates in xylanase elicitor perception in the tobacco plant, as well as in the Arabidopsis and Medicago truncatula plant tissues.[16]
See also
- Pain in amphibians
- Retrograde signaling
- Endocannabinoid system
- Evolutionary history of life
- Evolutionary history of plants
References
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{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ For example, note synonyms in PubChem for oleoylethanolamine.
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