N-Acylethanolamine

General chemical structure of N-acylethanolamines

An N-acylethanolamine (NAE) is a type of fatty acid amide where one of several types of acyl groups is linked to the nitrogen atom of ethanolamine, and highly metabolic formed by intake of essential fatty acids through diet by 20:4, n-6 and 22:6, n-3 fatty acids,[1][2] and when the body is physically and psychologically active,.[3][4] The endocannabinoid signaling system (ECS) is the major pathway by which NAEs exerts its physiological effects in animal cells with similarities in plants, and the metabolism of NAEs is an integral part of the ECS,[5] a very ancient signaling system, being clearly present from the divergence of the protostomian/deuterostomian,[6][7] and even further back in time, to the very beginning of bacteria, the oldest organisms on Earth known to express phosphatidylethanolamine, the precursor to endocannabinoids, in their cytoplasmic membranes. Fatty acid metabolites with affinity for CB receptors are produced by cyanobacteria, which diverged from eukaryotes at least 2000 Million years ago (MYA), by brown algae which diverged about 1500 MYA, by sponges, which diverged from eumetazoans about 930 MYA, and a lineages that predate the evolution of CB receptors, as CB1CB2 duplication event may have occurred prior to the lophotrochozoan-deuterostome divergence 590 MYA. Fatty acid amide hydrolase (FAAH) evolved relatively recently, either after the evolution of fish 400 MYA, or after the appearance of mammals 300 MYA, but after the appearance of vertebrates. Linking FAAH, vanilloid receptors (VR1) and anandamide (NAE 20:4) implies a coupling among the remaining ‘‘older’’ parts of the endocannabinoid system, monoglyceride lipase (MGL), CB receptors, that evolved prior to the metazoanbilaterian divergence (ie, between extant Hydra and leech), but were secondarily lost in the Ecdysozoa, and 2-Arachidonoylglycerol (2-AG).[8]

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.[9] 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.[10]

N-acylethanolamines (NAEs) are broken down, or hydrolysed, by fatty acid amide hydrolase (FAAH) to ethanolamine (MEA) and their corresponding fatty acid, arachidonic acid. FAAH is activated during stress exposure circumstances, which also raises the neuronal excitability in the amygdala, a critical brain area that mediates anxiety, and the anxiolytic outcome of CB1 receptor activation.[11] Inhibition of FAAH has been shown to increase the levels of NAEs in vivo and to produce desirable phenotypes, that produce analgesic, anxiolytic, neuroprotective, and anti-inflammatory effects,[12] like in high-level performance athletes (i.e., elite athletes) that present an extraordinary interindividual variability of physical, but also mental traits, that greatly influence their sports accomplishments and their career longevity, by an FAAH genetic polymorphism that produce the SNP rs324420 (C385A allele), associated with a higher sensitivity of FAAH to proteolytic degradation and a shorter half-life, as compared to the C variant, as the A variant displays normal catalytic properties, but an enhanced sensitivity to degradation, leading to increased NAE and anandamide (AEA) signaling.[11] Activation of the cannabinoid receptor CB1 or CB2 in different tissues, including skin, inhibit FAAH, and thereby increases endocannabinoid levels.[13]

  1. ^ Cite error: The named reference :25 was invoked but never defined (see the help page).
  2. ^ Galasso I, Russo R, Mapelli S, Ponzoni E, Brambilla IM, Battelli G, Reggiani R (20 May 2016). "Variability in Seed Traits in a Collection of Cannabis sativa L. Genotypes". Frontiers in Plant Science. 7: 688. doi:10.3389/fpls.2016.00688. PMC 4873519. PMID 27242881.
  3. ^ Charytoniuk T, Zywno H, Berk K, Bzdega W, Kolakowski A, Chabowski A, Konstantynowicz-Nowicka K (March 2022). "The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders". International Journal of Molecular Sciences. 23 (6): 3083. doi:10.3390/ijms23063083. PMC 8948925. PMID 35328503.
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  5. ^ Blancaflor EB, Chapman KD (2006). "Similarities Between Endocannabinoid Signaling in Animal Systems and N-Acylethanolamine Metabolism in Plants". In Baluška F, Mancuso S, Volkmann D (eds.). Communication in Plants: Neuronal Aspects of Plant Life. Berlin, Heidelberg: Springer. pp. 205–219. doi:10.1007/978-3-540-28516-8_14. ISBN 978-3-540-28516-8.
  6. ^ Fasano, Silvia; Meccariello, Rosaria; Cobellis, Gilda; Chianese, Rosanna; Cacciola, Giovanna; Chioccarelli, Teresa; Pierantoni, Riccardo (April 2009). "The Endocannabinoid System: An Ancient Signaling Involved in the Control of Male Fertility". Annals of the New York Academy of Sciences. 1163 (1): 112–124. Bibcode:2009NYASA1163..112F. doi:10.1111/j.1749-6632.2009.04437.x. PMID 19456333. S2CID 6304998.
  7. ^ Elphick, M. R.; Egertová, M. (2005), Pertwee, Roger G. (ed.), "The Phylogenetic Distribution and Evolutionary Origins of Endocannabinoid Signalling", Cannabinoids, Handbook of Experimental Pharmacology, no. 168, Berlin, Heidelberg: Springer, pp. 283–297, doi:10.1007/3-540-26573-2_9, ISBN 978-3-540-26573-3, PMID 16596778
  8. ^ McPartland, John M (1 April 2004). "Phylogenomic and chemotaxonomic analysis of the endocannabinoid system". Brain Research Reviews. 45 (1): 18–29. doi:10.1016/j.brainresrev.2003.11.005. ISSN 0165-0173. PMID 15063097. S2CID 25038370.
  9. ^ Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (February 2004). "Molecular characterization of a phospholipase D generating anandamide and its congeners". The Journal of Biological Chemistry. 279 (7): 5298–5305. doi:10.1074/jbc.M306642200. PMID 14634025.
  10. ^ For example, note synonyms in PubChem for oleoylethanolamine.
  11. ^ a b Silva, Hugo-Henrique; Tavares, Valéria; Silva, Maria-Raquel G.; Neto, Beatriz Vieira; Cerqueira, Fátima; Medeiros, Rui (26 March 2023). "Association of FAAH rs324420 (C385A) Polymorphism with High-Level Performance in Volleyball Players". Genes. 14 (6): 1164. doi:10.3390/genes14061164. ISSN 2073-4425. PMC 10298391. PMID 37372343. This article incorporates text from this source, which is available under the CC BY 4.0 license.
  12. ^ Hayes, Alexander C. (2013). "Identification of N-acylethanolamines in Dictyostelium discoideum and confirmation of their hydrolysis by fatty acid amide hydrolase". J. Lipid Res. 54 (2): 457–466. doi:10.1194/jlr.M032219. PMC 3588872. PMID 23187822.
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