Anandamide metabolism

Figure 6 Anandamide metabolism NAPE, N-arachidonylphosphatidyl-ethanol-amides PLD, phospholipase D AEA, anandamide AC, anandamide carrier protein AT, anandamide transporter AEAase, anandamide amidase AA, arachidonic acid.

Deutsch DG, Lin S, Hill WAG, Morse KL, Salehani D, Arreaza G, Omeir RL, Makriyannis A. Fatty acid sulfonyl fluorides inhibit anandamide metabolism and bind to the cannabinoid receptor. Biochem Biophys Res Com-mun 1997 231 217-221. 

Fig. 1. Targeted lipidomics of anandamide metabolism. Postulated pathways of anandamide metabolism. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine NAT, JV-acyl transferase LPA, lysophosphatidic acid PA, phosphatidic acid NAPE, jV-acyl-phosphatidylethanolamine Lyso-NAPE, l-lyso,2-acyl-OT-glycero-3-phosphoethanolamine-JV-acyl ABHD-4, a//3 hydrolase-4 GP-anandamide, glycerophospho-anandamide PAEA, phospho-anandamide PLA, phospholipase A NAPE-PLD, NAPE phospholipase D PLC, phospholipase C FAAH, fatty acid amide hydrolase P, phosphatase COX, cyclooxygenase LOX, lipoxygenase CYP450, cytochrome P450 PDE, phosphodiesterase.

Multiple lipid pathways take part in anandamide biosynthesis and degradation (Fig. 1). Here, we review the lipid components that constitute such networks and how they might interact to regulate anandamide metabolism. 

Snider, N. T., Kornilov, A. M., Kent, U. M., and Hollenberg, R F. (2007). Anandamide metabolism by human liver and kidney microsomal cytochrome P450 enzymes to form hydroxyeicosatetraenoic and epoxyeicosatrienoic acid ethanolamides. J. Pharmacol. Exp. Ther. 321, 590—597. 

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. 

Bomheim, L.M. Kim, K.Y. Chen, B. and Correia, M.A. The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism. Biochem Biophys Res Comm 197(2) 740-6, 1993. 

Smart D, Jonsson K-O, Vandevoorde S, Lambert DM, Fowler CJ (2002) Entourage effects of N-acyl ettianolamines at human vanilloid receptors. Comparison of effects upon anandamide-induced vanilloid receptor activation and upon anandamide metabolism. Br J Pharmacol 136 452-458... 

Maccarrone M, Valverde O, Barbaccia M L, Castane A, Maldonado R, Ledent C, Parmentier M, Finazzi-Agro A (2002) Age-related changes of anandamide metabolism in CBi cannabinoid receptor knockout mice correlation with behaviour. Eur J Neurosci 15 1178-1186... 

Bornheim LM, Kim KY, Chen B, and Correia MA (1995) Microsomal cytochrome P450-mediated liver and brain anandamide metabolism. Biochem Pharmacol 50 677-686. 

What is, then, the biogenesis of anandamide One of the aims of the present chapter is to review the last three years of research in this area and provide a possible answer to this question. I will also briefly describe what is currently known on other aspects of anandamide metabolism in brain tissue, in particular its hydrolytic degradation and oxygenation by lipoxygenase enzymes. Before we address these issues, however, it will be useful to review the biological effects of anandamide in the wider context of the multiple pharmacological properties of plant-derived and synthetic cannabinoid drugs. 

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