Structural and functional differences between cyclooxygenases: fatty acid oxygenases with a critical role in cell signaling.
Cyclooxygenase (COX) catalyzes the first two steps in the conversion of arachidonic acid (AA) to prostaglandins (PGs). The reaction mechanism is well-defined and supported by extensive structural data. There are two isoforms of COX, which are nearly indistinguishable in structure and mechanism, however, COX-2 oxygenates neutral derivatives of AA that are poor substrates for COX-1. The best neutral substrate is 2-arachidonylglycerol, oxygenation of which produces an array of prostaglandin glyceryl esters (PG-Gs) that is nearly as diverse as the PGs. The mobilization of Ca2+ by subnanomolar concentrations of PGE2-G in RAW264.7 cells suggests the existence of a distinct receptor, and the formation of PG-Gs by zymosan-stimulated macrophages indicates that these species may be formed in vivo. These findings suggest that PG-Gs comprise a new class of lipid mediators, and that oxygenation of neutral derivatives of AA is a distinct function for the COX-2 isoform.
Rouzer
Carol A
CA
Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Marnett
Lawrence J
LJ
D000818:Animals; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000502:physiology; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D005227:Fatty Acids; D007527:Isoenzymes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2