Multiple pathways involved in the biosynthesis of anandamide.

Liu J, Wang L, Harvey-White J, Huang BX, Kim HY, Luquet S, Palmiter RD, Krystal G, Rai R, Mahadevan A, Razdan RK, Kunos G
Neuropharmacology. 2008 54 (1): 1-7

PMID: 17631919 · PMCID: PMC2219543 · DOI:10.1016/j.neuropharm.2007.05.020

Endocannabinoids, including anandamide (arachidonoyl ethanolamide) have been implicated in the regulation of a growing number of physiological and pathological processes. Anandamide can be generated from its membrane phospholipid precursor N-arachidonoyl phosphatidylethanolamine (NAPE) through hydrolysis by a phospholipase D (NAPE-PLD). Recent evidence indicates, however, the existence of two additional, parallel pathways. One involves the sequential deacylation of NAPE by alpha,beta-hydrolase 4 (Abhd4) and the subsequent cleavage of glycerophosphate to yield anandamide, and the other one proceeds through phospholipase C-mediated hydrolysis of NAPE to yield phosphoanandamide, which is then dephosphorylated by phosphatases, including the tyrosine phosphatase PTPN22 and the inositol 5' phosphatase SHIP1. Conversion of synthetic NAPE to AEA by brain homogenates from wild-type and NAPE-PLD(-/-) mice can proceed through both the PLC/phosphatase and Abdh4 pathways, with the former being dominant at shorter (<10 min) and the latter at longer (60 min) incubations. In macrophages, the endotoxin-induced synthesis of anandamide proceeds uniquely through the phospholipase C/phosphatase pathway.

MeSH Terms (26)

Animals Arachidonic Acids Cell Line, Transformed Chromatography, High Pressure Liquid Chromatography, Thin Layer Drug Interactions Endocannabinoids Glycerophosphates Hydrolases Hydrolysis Inositol Polyphosphate 5-Phosphatases Lipopolysaccharides Macrophages Metabolic Networks and Pathways Mice Mice, Knockout Neomycin Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phospholipase D Phosphoric Monoester Hydrolases Polyunsaturated Alkamides Protein Synthesis Inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 22 RNA, Small Interfering Transfection Type C Phospholipases

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