The endogenous cannabinoid signaling system, comprised of endogenous cannabinoids, cannabinoid receptors, and the enzymes that synthesize and degrade the endogenous cannabinoids is much more complex than initially conceptualized. 2-arachidonoyl glycerol, 2-AG, is the most abundant endocannabinoid and plays a major role in CNS development and synaptic plasticity. Over the last decade many key players in 2-AG synthesis and degradation have been identified and characterized. Most 2-AG is synthesized from membrane phospholipids via sequential activation of a phospholipase Cβ and a diacylglycerol lipase, though other pathways may contribute in specialized settings. 2-AG breakdown is more complicated with at least eight different enzymes participating. These enzymes can either degrade 2-AG into its component arachidonic acid and glycerol, or transform 2-AG into highly bioactive signal molecules. The implications of the precise temporal and spatial control of the expression and function of these pleiotropic metabolizing enzymes has only recently come to be appreciated. In this review we will focus on the primary organization of 2-AG synthetic and degradative pathways and then discuss more recent findings and their implications, with an eye towards the biological and therapeutic implications of manipulating 2-AG synthesis and metabolism.
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PMID:

 

24102242

 

[PubMed – as supplied by publisher]