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Anandamide biosynthesis and metabolism


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Anandamide biosynthesis and metabolism

Anandamide biosynthesis and metabolism

During anandamide biosynthesys 1-arachidonoyl-2-stearoyl-sn-glycerol 3-phospho ethanolamineand 1,2-diarachidonoylphosphatidylcholine pass to a transacylation reactioncatalyzed by HRAS-like suppressor 5 ( HRSL5 ) [1] and also byArylamine N-acetyltransferase ( NAT ) that givesN,1-diarachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine and either2-arachidonoyl-glycerol 3-phosphocholine or1-arachidonoyl-sn-glycero-3-phosphocholine as products.

N,1-Diarachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine undergoesmultiple transformations. It can either be hydrolyzed byN-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D ( NAPE PLD ) to formdirectly Anandamide and also 1 -arachidonoyl-2-stearoyl-glycerol3-phosphate as a byproduct [2], [3], [4];either can be hydrolyzed by the action of various phospholipases (Phospholipase A2(PLA2(hGIIA) ), Cytosolic phospholipase A2 ( PA24A ), Group 10 secretoryphospholipase A2 precursor ( PLA2G10 ), Calcium-dependent phospholipase A2precursor ( PLA2G5) ) to form Arachidonic acid andN-arachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine [5],[6], [7]. The same metabolite is formed in when HRSL5catalyses the intramolecular transacylation of 1-arachidonoyl-2-stearoyl-sn-glycerol 3-phospho ethanolamine[1]. 

Another way is degradation under the action of Phospholipase A2 precursor (PLA2G1B ) with N,1-diarachidonoyl-sn-glycerol 3-phosphoethanolaminemetabolite and Stearic acid as a byproduct [5]. Ectonucleotidepyrophosphatase/phosphodiesterase family member 2 precursor ( ENPP2 ) acts onN,1-diarachidonoyl-sn-glycerol 3-phosphoethanolamine causing its hydrolysis whatleads to the production of Anandamide and 1-arachidonoyl-glycerol3-phosphate [5]. 1-arachidonoyl-glycerol 3-phosphate can also beformed during ENPP2 catalyzed 1-arachidonoyl-glycerol 3-phosphatehydrolysis and 2-arachidonoyl-glycerol 3-phosphate is formed during an analogousprocess with 2-arachidonoyl-glycerol 3-phosphocholine as a substrate. Bothprocesses give Choline as a byproduct [8], [9], [10], [11], [12].

Finally, N,1-diarachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine can behydrolyzed by a set of phospholipases ( PLC-delta, PLC-gamma,phospholipase C, zeta 1 ( PLC-zeta ), PLC-beta,1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 ( PLC-epsilon)) to form 1-arachidonoyl-2-stearoyl-sn-glycerol and phosphoanandamide[13]. Phosphoanandamide is subjected to phosphatase activity ofTyrosine-protein phosphatase non-receptor type 22 ( 70Z-PEP ) andAnandamide together with a phosphate unit are formed [13].

ENPP2 catalyzes the subsequent hydrolysis ofN-arachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine producingAnandamide and 2-stearoyl-sn-glycerol 3-phosphate as a byproduct [5].

Anandamide is metabolized by Fatty-acid amide hydrolase 1 ( FAAH ) andthe products are Arachidonic acid and Ethanolamine [14], [15], [16].