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

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].

Further reading

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References

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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 24/07/2017. 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 N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.