Abstract
Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic “N-acylationphosphodiesterase pathway” for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.
Keywords: N-Acylethanolamine, anandamide, biosynthesis, NAPE-PLD, oleoylethanolamide, palmitoylethanolamide, phospholipid, plasmalogen
CNS & Neurological Disorders - Drug Targets
Title:Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain
Volume: 12 Issue: 1
Author(s): Kazuhito Tsuboi, Natsuki Ikematsu, Toru Uyama, Dale G. Deutsch, Akira Tokumura and Natsuo Ueda
Affiliation:
Keywords: N-Acylethanolamine, anandamide, biosynthesis, NAPE-PLD, oleoylethanolamide, palmitoylethanolamide, phospholipid, plasmalogen
Abstract: Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic “N-acylationphosphodiesterase pathway” for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.
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Tsuboi Kazuhito, Ikematsu Natsuki, Uyama Toru, G. Deutsch Dale, Tokumura Akira and Ueda Natsuo, Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain, CNS & Neurological Disorders - Drug Targets 2013; 12 (1) . https://dx.doi.org/10.2174/1871527311312010005
DOI https://dx.doi.org/10.2174/1871527311312010005 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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