2-Arachidonoyl-diacylglycerols

As in the case of anandamide, 2-AG is derived from the hydrolysis of complex membrane lipids. The direct precursors of 2-AG can either be 1-acyl, 2-arachidonoyl-diacylglycerols (DAGs) or 2-arachidonoyl-lysoglycerophospholi-pids (e.g., lysophosphatidic acid, LPA). 

Anandamide is believed to be synthesized from a phospholipid precursor, /V-arachidonoyl-phosphatidylethanolamine, catalysed by phospholipase D (Di Marzo et al. 1998). The other proposed route of synthesis is from condensation of arachidonic acid and ethanolamine, although this has yet to be demonstrated in living cells. 2-AG is formed in a calcium-dependent manner, and mediated by the enzymes phospholipase C and diacylglycerol lipase (Kondo et al. 1998 Stella et al. 1997). 

AA arachidonic acid, 2-AG 2-arachidonoyl glycerol, DHA docosahexaenoic add, FAAH fatty add amide hydrolase, DAGL sn-1-selective diacylglycerol lipase, MAGL monoacylglycerol lipase, NAPE-PLD N-acylphosphatidylethanolamine-selective phospholipase D... 

S ATP + l-stearoyl-2-arachidonoyl-sn-glycerol <5> (<5>, since diacylglycerol kinase is an enzyme of the phosphatidylinositol cycle, its natural substrate could be l-stearoyl-2-arachidonoyl-sn-glycerol, thought to be the main diacylglycerol analog generated from phosphoinositide [7]) (Reversibility <5> [7]) [7]... 

Prescott, S.M. and Majerus, P.W. (1983) Characterization of 1,2-diacylglycerol hydrolysis in human platelets. Demonstration of an arachidonoyl-monoacylglycerol intermediate. Journal of Biological Chemistry 258 764-769. 

Based on this fact and in the presence of active phosphoinositide phosphodiesterases, these authors proposed a relationship between arachidonoyl diglycerides and the phosphoinositides in the central nervous system. The rapid production of diacylglycerols enriched in 18 0-20 4 that takes place in the mammalian brain during ischemia (Aveldano Bazan, 1975), may be related to this possibility. By analogy we suggested that such a metabolic link might also be present in the mammalian retina (Aveldano Bazan, 1974). 

The fact that phosphatidylinositol has a fatty acid composition which is very different from that of the other phospholipids of pancreas was used to test whether the newly-formed phosphatidic acid in the stimulated tissue was derived from phosphatidylinositol (Geison et al., 1976). The structure of phosphatidylinositol from other mammalian tissues has been shown to be 1-stearoyl, 2-arachidon-oyl-sn-glycero-3-phosphorylinositol (Holub Kuksis, 1971 Baker Thompson, 1972), We find that this fatty acid composition is also typical of pancreas phosphatidylinositol. Lipid-soluble products of phosphatidylinositol which retain the diacylglycerol moiety should therefore contain stearic and arachidonic acids in equal proportions. In pancreas tissue incubated with acetylcholine, there is stoichiometry between the amounts of stearic and arachidonic acids which are lost from the phosphatidylinositol fraction and the amounts which appear in the phosphatidic acid fraction. The newly-formed phosphatidic acid appears therefore to have the same fatty acid composition as the phosphatidylinositol which is broken down. It presumably contains the 1-stearoyl, 2-arachidonoyl glycerol moiety which was originally in phosphatidylinositol. I shall use the prefix (18 0,20 4) to denote lipids which contain this moiety. The (18 0,20 4)phosphatidic acid which is formed in stimulated tissue is a novel species there is very little stearic acid and arachidonic acid in the phosphatidic acid from unstimulated pancreas. 

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