IUPHAR/BPS Guide to Pharmacology CITE

Endocannabinoid turnover (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Stephen P.H. Alexander1, Patrick Doherty2, Christopher J. Fowler3, Jürg Gertsch4 and Mario van der Stelt5
  1. University of Nottingham, UK
  2. King's College London, UK
  3. University Hospital of Umeå, Sweden
  4. University of Bern, Switzerland
  5. Leiden University, The Netherlands


The principle endocannabinoids are 2-acylglycerol esters, such as 2-arachidonoylglycerol (2-AG), and N-acylethanolamines, such as anandamide (N-arachidonoylethanolamine, AEA). The glycerol esters and ethanolamides are synthesised and hydrolysed by parallel, independent pathways. Mechanisms for release and re-uptake of endocannabinoids are unclear, although potent and selective inhibitors of facilitated diffusion of endocannabinoids across cell membranes have been developed [19]. FABP5 (Q01469) has been suggested to act as a canonical intracellular endocannabinoid transporter in vivo [12]. For the generation of 2-arachidonoylglycerol, the key enzyme involved is diacylglycerol lipase (DAGL), whilst several routes for anandamide synthesis have been described, the best characterized of which involves N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD, [49]). A transacylation enzyme which forms N-acylphosphatidylethanolamines has recently been identified as a cytosolic enzyme, PLA2G4E (Q3MJ16) [43]. In vitro experiments indicate that the endocannabinoids are also substrates for oxidative metabolism via cyclooxygenase, lipoxygenase and cytochrome P450 enzyme activities [4, 16, 51].


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Database links

Endocannabinoid turnover
    N-Acylethanolamine turnover
                NAPE-PLD(N-Acylphosphatidylethanolamine-phospholipase D)
                FAAH(Fatty acid amide hydrolase)
                FAAH2(Fatty acid amide hydrolase-2)
                NAAA(N-Acylethanolamine acid amidase)
    2-Acylglycerol ester turnover
                DAGLα(Diacylglycerol lipase α)
                DAGLβ(Diacylglycerol lipase β)
                MAGL(Monoacylglycerol lipase)
                ABHD6(αβ-Hydrolase 6)
                αβ-Hydrolase 12


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