Anandamide oxidative metabolism

Burstein, S.H., Rossetti, R.G., Yagen, B., and Zurier, R.B. (2000) Oxidative metabolism of anandamide, Prostaglandins and Other Lipid Mediators 61 29-41. 

FIGURE 12.2 Oxidative metabolism of anandamide by cyclooxygenase (COX) and lipoxygenase (LOX) to yield ethanolamide (EA) derivatives. 

Endocannabinoids include arachidonylethanolamine, noladin, arachidonyldopa-mine, 2-arachidonylglycerol (2-AG), and arachidonylethanolamide (anandamide) (Fig. 7.8). 2-AG and anandamide are derived from the non-oxidative metabolism of arachidonic acid (ARA). 2-AG and anandamide are synthesized through... 

The close structural resemblance of anandamide and arachi-donic acid has prompted a series of biochemical experiments to test the possibility that anandamide serves as a substrate for enzymes that metabolize the polyunsaturated fatty acid. These experiments have considerable interest because, in principle, oxidative metabolism may modify the biological properties of anandamide—for example, change its affinity for cannabinoid receptors. 

There is some evidence that in cells with low anandamide amidase activity, such as platelets and neutrophils, anandamide is inactivated by an oxidative pathway involving 12(5)-lipoxygenase (Edgemond, 1998). Metabolism of anandamide by enzymes of the arachidonic acid cascade... 

Arachidonic acid is also a substrate for the cytochrome family of oxidative enzymes as might be expected from its polyunsaturated character. A number of cytochrome metabolites have been found, some of which are shown below (Figure 8.6). Interestingly, anandamide appears to exhibit a similar course of metabolism vide infra). 

Other metabolic routes involve oxidative transformations that bear close resemblance to the processes that lead to the eicosanoids (Kozak et al., 2000 Kozak, Crews, et al., 2001 Kozak, Prusakiewicz, et al., 2001 Kozak, Crews, et al., 2002 Kozak and Mamett, 2002). For example, both 12- and 15-lipoxygenase products of anandamide are known (Edgemond et al., 1998 Moody et al., 2001 Kozak, Gupta, et al., 2002), as well as a group of P-450-mediated hydroxy anandamide metabolites (Bomheim et al., 1993 Bomheim et al., 1995). Free arachidonic acid is required for COX-1-mediated conversion to PGs, whereas the requirements for COX-2-mediated conversion... 

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