Cannabinoids Anandamide & 2-AG | Synthesis & Degradation

Flow chart: The main pathways of synthesis and degradationof cannabinoids anadamide and 2-AG.

Cannabinoids Anandamide & 2-Arachidonoylglycerol (2-AG)- Synthesis & Degradation  

Endocannabinoids are lipid molecules which are derived from membrane phospholipids. They are substances that attach or activate the endocannabinoid system. Cannabinoids come from three main sources:

Neuromodulators & Retrograde Messengers

endocannabinoids act as neuromodulators and retrograde messengers affecting the release of calcium ions, potassium ions, as well as other neurotransmitters. Unlike with classical neurotransmitters and neuropeptides, endocannabinoids are synthesized on demand in somata and dendrites. They are subsequently released from the cells and then immediately signal molecules.

There are two major endocannabinoids identified which have been studied the most in the central nervous system: arachidonoylethanolamide (AEA), which is commonly known as anandamide, and 2-arachidonoylglycerol (2-AG) which are synthesized and degraded by separate pathways. However, it’s thought that the body produces several other endocannabinoids as well. They modulate metabolism, mood, appetite, bone growth, pain, inflammation, memory, sleep, muscle tone, and function of immunity. See the figure below. 

Flow chart: The main pathways of synthesis and degradationof cannabinoids anadamide and 2-AG.

Cannabinoid |Anadamide

The cannabinoid anandamide gets its name from the Sanskrit word ananda which means “joy” or “bliss”. Anandamid is also known as N-arachidonoylethanolamine, or AEA. anandamide- a fatty acid which is derived from N-arachidonoyl phospatidylethoanolamine (NAPE), which is generated by the enzyme N-acyltransferase in a calcium-dependent manner. anandamide is then generated by hydrolysis of NAPE by a phospholipase D (NAPE-PLD). Unlike some neuromodulators which are produced and stored in small vesicles until they are needed, AEA is not stored in the body, but is produced in very small amounts-only at the time when it is needed. Animal studies have shown a possibility that the production of anandamide just might be influenced by diet anandamide binds to both the CB1 And CB2 receptors. This lipophilic (fat-loving) molecule gets transported into the cell and is broken down by hydrolysis into the by-product’s arachidonic acid and ethanolamine. 

Cannabinoid | 2-Arachidonoylglycerol (2-AG)

There’s another type of cannabinoid which is 2-arachidonoylglycerol (2-AG), which is an ester formed from arachidonic acid and glycerol. Its synthesis depends on calcium  and the activity of enzymes phospholipase C (PLC) and diacylglycerol lipase (DAGL). In comparison to anandamide, it presents much higher levels in the central nervous system and attaches to CB1 receptors. It is also transported by carrier proteins in to the cell, where it gets broken down by hydrolysis

Summarizing Main Pathways of Synthesis and Degradation of Cannabinoids Anandamide and 2-AG

To summarize the main pathways of synthesis and degradation of Cannabinoids anandamide and 2-AG, the synthesizing and releasing of these two endogenous Cannabinoids occurs on demand in an active dependent manner, by either the firing of neurons or activation of G-protein-coupled receptors, or a combination of both.   

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