Fatty acid amide hydrolase anandamide hydrolysis

Both anandamide and 2-AG are inactivated by enzymatic hydrolysis (Goparaju et al. 1998). Fatty acid amide hydrolase (FAAH) is an enzyme that catalyses their hydrolysis. High concentrations of FAAH were found in the cerebellum, hippocampus and neocortex of rat brain, which are also rich in cannabinoid receptors. Further, there is a complementary pattern of distribution of FAAH and the CBl receptor. For example, in the cerebellum, FAAH is found in the cell bodies of Purkinje cells and the CBl receptor is found in the axons of granule cells and basket cells, which are presynaptic to Purkinje cells. 2-AG may also be inactivated by direct esterification into membrane phospholipids. Cannabinoid Receptors... 

Anandamide can be hydrolyzed to arachidonic acid and ethanolamine by fatty acid amide hydrolase (FAAH) (Cravatt et al., 1996 Wei et al., 2006) (Fig. 1). FAAH is highly expressed in the brain, where it is expressed at high concentrations in neuronal cell bodies and dendrites that are juxtaposed to axon terminals containing CB receptors. This suggests that anandamide hydrolysis occurs post-synaptically (Piomelli, 2003). 

Fegley, D., Kathuria, S., Mercier, R., Li, C., Goutopoulos, A., Makriyannis, A., and Piomelli, D. (2004). Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AMI 172. Proc. Natl. Acad. Sci. USA 101, 8756—8761. 

Kurahashi, Y, Ueda, N., Suzuki, H., Suzuki, M., and Yamamoto S. (1997) Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase. Biochemical and Biophysical Research Communications 237 512-515. 

Both anandamide and 2-AG can be degraded by hydrolysis or oxidation. The hydrolysis of endocannabinoids is catalyzed by fatty acid amide hydrolase (FAAH), an enzyme which cleaves the amide bond of anandamide and the ester bond of 2-AG. Molecular details of the binding of endocaruiabinoids to FAAH are given in Chapter 5. Nevertheless, although FAAH may hydrolyze 2-AG in vitro, it turned out that in the brain, tiiis enzyme is not involved in 2-AG degradation. In vivo, more than 80% of 2-AG is hydrolyzed by another enzyme. 

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