Endocannabinoid system enzymes and transport (ECS enzymes and transporters)

The endocannabinoid system (ECS) enzymes and transport machinery constitute the metabolic framework that regulates the levels of endogenous cannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) [1, 2]. This system includes degradative enzymes like Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol Lipase (MAGL), as well as biosynthetic enzymes like N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) [3, 4]. Additionally, transport mechanisms involving Fatty Acid Binding Proteins (FABPs) and putative membrane transporters facilitate the movement of these lipophilic ligands to their metabolic sites [5]. Pharmacological targeting of these enzymes, particularly FAAH and MAGL inhibitors, aims to elevate local endocannabinoid concentrations to provide analgesic, anti-inflammatory, and anxiolytic effects [6]. This approach is considered a promising therapeutic strategy for various conditions, including chronic pain, neurodegenerative diseases, and mood disorders, potentially offering a better safety profile than direct cannabinoid receptor agonists [7]. Citations: [1] Piomelli D. (2003). Nature Reviews Neuroscience. 4(11):873-884. [2] Fowler CJ. (2012). British Journal of Pharmacology. 166(5):1568-1585. [3] Ueda N, et al. (2013). Progress in Lipid Research. 52(4):427-435. [4] Bisogno T, et al. (2003). Journal of Cell Biology. 163(3):463-468. [5] Kaczocha M, et al. (2009). PNAS. 106(15):6375-6380. [6] Chicca A, et al. (2017). British Journal of Pharmacology. 174(14):2265-2281. [7] Di Marzo V. (2018). Nature Reviews Drug Discovery. 17(9):623-639.

Other names

Endocannabinoid metabolic enzymesEndocannabinoid transport systemECS metabolic pathwaysEndocannabinoid turnover proteinsFatty acid amide hydrolaseMonoacylglycerol lipaseN-acyl phosphatidylethanolamine-specific phospholipase DDiacylglycerol lipase

Inhibition of endocannabinoid degradation and transport to increase endogenous ligand levels