Critical Enzymes Involved in Endocannabinoid Metabolism

^{Division of Analytical Psychopharmacology, New York State Psychiatric Institute}

^{Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA}

^{Nathan Kline Institute for Psychiatric Research, Orangeburg, Orangeburg, NY 10962, USA}

*Address correspondence to this author at the Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY-10962, USA; Tel: 845-398-3234 or 5454; Fax: 845-398-5451; E-mail: gro.hmfr.ikn@jaravasaB

Abstract

Investigations of the pathways involved in the metabolism of endocannabinoids have grown exponentially in recent years following the discovery of cannabinoid receptors (CB) and their endogenous ligands, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG). The in vivo biosynthesis of AEA has been shown to occur through several pathways mediated by N-acylphosphatidylethanolamide-phospholipase D (NAPE-PLD), a secretory PLA₂ and PLC. 2-AG, a second endocannabinoid is generated through the action of selective enzymes such as phosphatidic acid phsophohydrolase, diacylglycerol lipase (DAGL), phosphoinositide-specific PLC (PI-PLC) and lyso-PLC. A putative membrane transporter or facilitated diffusion is involved in the cellular uptake or release of endocannabinoids. AEA is metabolized by fatty acid amidohydrolase (FAAH) and 2-AG is metabolized by both FAAH and monoacylglycerol lipase (MAGL). The author presents an integrative overview of current research on the enzymes involved in the metabolism of endocannabinoids and discusses possible therapeutic interventions for various diseases, including addiction.

Keywords: FAAH, Endocannabinoids, CNS, NAPE-PLD, MAGL, CB1 receptors, alcohol-drinking behavior, therapy

Abstract

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