Endocannabinoid turnover C

Overview

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The principle endocannabinoids are 2-acylglycerol esters, such as 2-arachidonoylglycerol (2AG), 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 (and related entities) are unclear, although candidates for intracellular transport have been suggested. For the generation of 2-arachidonoylglycerol, the key enzyme involved is diacylglycerol lipase (DGL), whilst several routes for anandamide synthesis have been described, the best characterized of which involves N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD, [9]). A transacylation enzyme which forms N-acylphosphatidylethanolamines has recently been identified as a cytosolic enzyme, PLA2G4E (Q3MJ16) [7]. In vitro experiments indicate that the endocannabinoids are also substrates for oxidative metabolism via cyclooxygenase, lipoxygenase and cytochrome P450 enzyme activities [1,3,10].

Subfamilies

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Comments

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Many of the compounds described as inhibitors are irreversible and so potency estimates will vary with incubation time. FAAH2 is not found in rodents [12] and a few of the inhibitors described have been assessed at this enzyme activity. 2-Arachidonoylglycerol has been reported to be hydrolysed by multiple enzyme activities from neural preparations, including ABHD2 (P08910) [6], ABHD12 (Q8N2K0) [2], neuropathy target esterase (PNPLA6, Q8IY17 [5]) and carboxylesterase 1 (CES1, P23141 [13]). ABHD2 (P08910) has also been described as a triacylglycerol lipase and ester hydrolase [4], while ABHD12 (Q8N2K0) is also able to hydrolyse lysophosphatidylserine [11]. ABHD12 (Q8N2K0) has been described to be inhibited selectively by triterpenoids, such as betulinic acid [8].

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Stephen Alexander, Patrick Doherty, Christopher Fowler. Endocannabinoid turnover. Accessed on 10/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=943.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.