Philip Kingsley
Last active: 3/12/2020

Selective oxygenation of N-arachidonylglycine by cyclooxygenase-2.

Prusakiewicz JJ, Kingsley PJ, Kozak KR, Marnett LJ
Biochem Biophys Res Commun. 2002 296 (3): 612-7

PMID: 12176025 · DOI:10.1016/s0006-291x(02)00915-4

Nonsteroidal anti-inflammatory drugs prevent hyperalgesia and inflammation by inhibiting the cyclooxygenase-2 (COX-2) catalyzed oxygenation of arachidonic acid to prostaglandin (PG) H(2). The lipoamino acid N-arachidonylglycine (NAGly) has also been shown to suppress tonic inflammatory pain and is naturally present at significant levels in many of the same mammalian tissues that express COX-2. Here, we report that COX-2 selectively metabolizes NAGly to PGH(2) glycine (PGH(2)-Gly) and hydroxyeicosatetraenoic glycine (HETE-Gly). Site-directed mutagenesis experiments identify the side pocket residues of COX-2, especially Arg-513, as critical determinants of the COX-2 selectivity towards NAGly. This is the first report of a charged arachidonyl derivative that is a selective substrate for COX-2. These results suggest a possible role for COX-2 in the regulation of NAGly levels and the formation of a novel class of eicosanoids from NAGly metabolism.

MeSH Terms (13)

Animals Arachidonic Acids Binding Sites Cyclooxygenase 2 Glycine Hydroxyeicosatetraenoic Acids Isoenzymes Kinetics Models, Molecular Oxygen Prostaglandin-Endoperoxide Synthases Prostaglandins Substrate Specificity

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