Chemical properties of 2-AG

2-AG is a member of a group of molecules that derive from arachidonic acid or two other 20-carbon essential fatty acids (EFAs) known as EPA and DGLA. These molecules, known as eicosanoids, are all oxidised versions of these 20-carbon (containing 20 carbon atoms per molecule) EFAs, and play a complex and important role in various bodily processes including immunity and inflammation.

The chemical formula for 2-AG, which can be classed as a fatty acid ester of glycerol as it converts the hydroxyl group of glycerol into a carboxyl group, has the molecular formula C23H38O4 and a molar mass of 378.3 g/mol. Due to its long hydrocarbon tail, the molecule can easily be broken down by the actions of lipid metabolism enzymes.

Synthesis and degradation of 2-AG

2-AG is formed similarly to anandamide—through the reaction of arachidonic acid with another endogenous molecule—although unlike anandamide, 2-AG requires glycerol rather than a free amine to make the chemical changes required.

However, rather than directly synthesising from the degradation of arachidonic acid, 2-AG is formed when the arachidonic acid-containing phospholipid diacylglycerol (DAG) reacts with glycerol. The enzyme that facilitates this process is known as the DAG lipase.

2-AG is degraded by monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH, also responsible for the degradation of anandamide) and several uncharacterised enzymes. It is believed that MAGL is responsible for up to 85% of this degradation process.

Physiological effects of 2-AG

2-AG is the most abundant endocannabinoid found in the body, and like anandamide, is thought to play an important role in the regulation of appetite, immune system functions and pain management. It is also thought that 2-AG may also play a role in the inhibition of cancer cell proliferation.