Which enzymes degrade the CB1-specific endogenous cannabinoid 2-arachidonyl glyceryl ether? (Noladin ether)
Noladin is an endocannabinoid. The best-characterised members of this family of molecules are Arachidonoylethanolamine (AEA; anandamide) and 2-arachidonoylglycerol (2-AG). The degradation of these endocannabinoids is reviewed in:
Pamplona, FA et al. (2012) Psychopharmacology of the endocannabinoids: far beyond anandamide. Journal of Psychopharmacology 26:7-22
These endocannabinoids are inactivated via a reuptake system that is present in both neuronal and glial cells, although the protein responsible has apparently not been identified.
AEA is then metabolised to arachidonic acid and ethanolamine by fatty acid amide hydrolase, while 2-AG is converted to arachidonic acid and glycerol by monoacylglycerol lipase.
Because of its ether linkage, noladin cannot be a substrate for either of these enzymes. However the review also describes other possible pathways of endocannabinoid metabolism involving oxidation by cyclooxygenases, lipoxygenases and P450 cytochromes. These are the best candidates for the further metabolism of noladin, but there is apparently no direct evidence for this.