title: Endocannabinoid metabolism by cytochrome P450 monooxygenases.
abstract: The endogenous cannabinoid system was first uncovered following studies of the recreational drug Cannabis sativa. It is now recognized as a vital network of signaling pathways that regulate several physiological processes. Following the initial discovery of the cannabinoid receptors 1 (CB1) and 2 (CB2), activated by Cannabis-derived analogs, many endogenous fatty acids termed "endocannabinoids" are now known to be partial agonists of the CB receptors. At present, the most thoroughly studied endocannabinoid signaling molecules are anandamide (AEA) and 2-arachidonylglycerol (2-AG), which are both derived from arachidonic acid. Both AEA and 2-AG are also substrates for the eicosanoid-synthesizing pathways, namely, certain cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes. In the past, research in the endocannabinoid field focused on the interaction of AEA and 2-AG with the COX and LOX enzymes, but accumulating evidence also points to the involvement of CYPs in modulating endocannabinoid signaling. The focus of this review is to explore the current understanding of CYP-mediated metabolism of endocannabinoids.
authors.affiliation: Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Zelasko
authors.affiliation: Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Arnold
authors.affiliation: Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States; Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL 61802, United States. Electronic address: aditidas@illinois.edu.
authors.forename: Aditi
authors.initials: A
authors.lastname: Das
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D063388:Endocannabinoids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism
chemical_list: C588309:CNR2 protein, human; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D003577:Cytochrome P-450 Enzyme System
keywords: 2-Arachidonylglycerol; Anandamide; CYP2J2; Cytochrome P450s; Eicosanoids; Endocannabinoids