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Mammalian enzymes responsible for the biosynthesis of N-acylethanolamines
Affiliation:1. Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan;2. Department of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan;1. Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Bruxelles, Belgium;2. Center for Drug Discovery, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, United States;3. Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States;1. Laboratory of Plantation Crops, Institute of Tropical Agriculture, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia;2. Department of Agriculture Technology, Faculty of Agriculture, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia;3. Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia;4. Advanced Biotechnology and Breeding Centre, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, B. B. Bangi, 43000 Kajang, Selangor, Malaysia
Abstract:Bioactive N-acylethanolamines (NAEs) are ethanolamides of long-chain fatty acids, including palmitoylethanolamide, oleoylethanolamide and anandamide. In animal tissues, NAEs are biosynthesized from membrane phospholipids. The classical “transacylation-phosphodiesterase” pathway proceeds via N-acyl-phosphatidylethanolamine (NAPE), which involves the actions of two enzymes, NAPE-generating Ca2+-dependent N-acyltransferase (Ca-NAT) and NAPE-hydrolyzing phospholipase D (NAPE-PLD). Recent identification of Ca-NAT as Ɛ isoform of cytosolic phospholipase A2 enabled the further molecular biological approaches toward this enzyme. In addition, Ca2+-independent NAPE formation was shown to occur by N-acyltransferase activity of a group of proteins named phospholipase A/acyltransferases (PLAAT)-1–5. The analysis of NAPE-PLD-deficient mice confirmed that NAEs can be produced through multi-step pathways bypassing NAPE-PLD. The NAPE-PLD-independent pathways involved three members of the glycerophosphodiesterase (GDE) family (GDE1, GDE4 and GDE7) as well as α/β-hydrolase domain-containing protein (ABHD)4. In this review article, we will focus on recent progress made and latest insights in the enzymes involved in NAE synthesis and their further characterization.
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