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 )  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 , , ;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 ,, . The same metabolite is formed in when HRSL5catalyses the intramolecular transacylation of 1-arachidonoyl-2-stearoyl-sn-glycerol 3-phospho ethanolamine. 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 . 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 . 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 , , , , . 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. Phosphoanandamide is subjected to phosphatase activity ofTyrosine-protein phosphatase non-receptor type 22 ( 70Z-PEP ) andAnandamide together with a phosphate unit are formed . ENPP2 catalyzes the subsequent hydrolysis ofN-arachidonoyl-2-stearoyl-sn-glycerol 3-phosphoethanolamine producingAnandamide and 2-stearoyl-sn-glycerol 3-phosphate as a byproduct . Anandamide is metabolized by Fatty-acid amide hydrolase 1 ( FAAH ) andthe products are Arachidonic acid and Ethanolamine , , .