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Updated: Jan 12, 2026

Prostaglandin Extraction and Analysis in Caenorhabditis elegans
Published on: June 25, 2013
Endocannabinoid oxygenation by prostaglandin H synthase-2: Chemistry and biology
Carol A Rouzer1, Lawrence J Marnett1
1Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine Basic Sciences, Nashville Tennessee, USA.
Abstract:
Prostaglandin (PG) endoperoxide synthases (PGHS)-1 and -2 oxygenate arachidonic acid to PGH2, the precursor to PGs and thromboxane. PGHS-2 also oxygenates ester and amide substrates more efficiently than PGHS-1. Foremost among these neutral substrates are the endocannabinoids, arachidonoylethanolamide and 2-arachidonoylglycerol (2-AG). 2-AG is the most abundant endocannabinoid and a full agonist for both cannabinoid receptors, CB1 and CB2. PGHS-2-mediated oxygenation of 2-AG ultimately produces PG glycerol esters, which exhibit biological activities largely independent of classical endocannabinoid and PG receptors. This article reviews the mechanism of PGHS-2 oxygenation of 2-AG, the kinetic and structural basis for its biochemical regulation, the occurrence of 2-AG oxygenation in cells and in vivo, and the biological impact of the pathway. Gaps in our knowledge and challenges to a fuller understanding of the impact of PGHS-2 oxygenation of 2-AG are presented.
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