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:Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
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.
