Biosynthesis of anandamide and 2-arachidonoylglycerol

Abstract

Anandamide (N-arachidonoylethanolamine) can be synthesized from free arachidonic acid and ethanolamine by the action of a fatty acid amide hydrolase acting in reverse or from preexisting N-arachidonoyl phosphatidylethanolamine by the action of a phosphodiesterase (phospholipase D). Evidence is accumulating that anandamide is synthesized mainly by the latter pathway rather than the former in various mammalian tissues and cells. 2-Arachidonoylglycerol can be synthe sized from arachidonic acid-containing diacylglycerol derived from increased inositol phospholipid metabolism by the action of a diacylglycerol lipase. 2-Arachidonoylglycerol can also be formed via other pathways such as the hydrolysis of the diacylglycerol derived from phosphatidylcholine and phosphatidic acid by the action of a diacylglycerol lipase and the hydrolysis of arachidonic acid- containing lysophosphatidic acid by the action of a phosphatase. The relative importance of these pathways may depend on the types of cells and stimuli. In this review, I have summarized the pathways and enzymes involved in the synthesis of anandamide and 2-arachidonoylglycerol.