Methyl arachidonyl

The enzyme FAAH was first identified in the 1980s [39], cloned in the 1990s [25] and more recently, the crystal structure [40] of FAAH bound to methyl arachidonyl phosphonate has been published. The FAAH enzyme has wide substrate specificity capable of catalysing the hydrolysis of a wide variety of... 

YC Lio, LJ Reynolds, J Balsinde, EA Dennis. Irreversible inhibition of Ca(2 + )-independent phospholipase A2 by methyl arachidonyl fluorophosphonate. Biochim... 

Anandamide is rapidly hydrolysed enzymatically to arachidonic acid and ethanol-amine by a fatty acid amide hydrolase (FAAH) [50], The molecular characterization, cloning and expression of FAAH have been reported in a recent study [51]. FAAH can be blocked with either the general serine protease inhibitor phenyl methy(sulphonyl fluoride [38] or with the highly efficient methyl arachidonyl fluorophsphonate [52], The non-steroidal antiinflammatory ibuprofen in therapeutic doses, but not aspirin, sulindac or acetaminophen, also inhibits anandamide metabolism [53], This observation may have therapeutic implications. 

PA-PLAi was inhibited by methyl arachidonyl fluorophosphonate (MAFP), an inhibitor of certain PLA2S, but not by DFP [39], which is a potent inhibitor of mPA-PLAi. The activity of PA-PLAi was Ca -independent at neutral pH but Ca -dependent at alkaline pH [39]. 

Deutsch DG, Omeir R, Arreaza G, Salehani D, Prestwich GD, Huang Z, Howlett A (1997b) Methyl arachidonyl fluorophosphonate a potent irreversible inhibitor of anandamide amidase. Biochem Pharmacol 53 255-260... 

Fernando SR, Pertwee RG (1997) Evidence that methyl arachidonyl fluorophosphonate is an irreversible cannabinoid receptor antagonist. Br J Pharmacol 121 1716-1720... 

Fig. 5.2 Chemical structures of arachidonyltrifluoromethyl ketone (a) methyl arachidonyl fluo-rophosphonate (b) calpeptin (c) and E-64-d ((2S,3S)-trans-epoxysuccinyl-L-3-methylbutaneethyl ester) (d)...

Dose-dependent generalization to A -THC was observed upon administration of the metabolically stable analogs of anandamide, (R)-methanandamide (37,38), or 2-methyl-arachidonyl-2 -fluoroethylamide( 5i>). 

Fig. 7.9 Generation of JV-acylethanolamine (NAE) and A-acylphosphatidylethanolamine (NAPE) in brain. Phosphatidylcholine (PtdCho) phosphatidylethanolamine (PtdEtn) cannabinoid lecep-torl (CBj-R) JV-methyl-D-aspartate receptor (NMDA-R) tmandamide and 2-arachidonyl-gltcerol not only stimulate CBi-R but also have stabilizing effects on neural membranes. TBI increases the formation of NAE and NAPE. Ai-arachidonylethanolamine stimulate ceramide formation, N-acylethanolamine inhibit ceramidase. Ceramide induces apoptosis. Plus sign indicate stimulation and minus sign indicates inhibition, (f) Indicate increase in levels...

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