Differential Sensitivity and Mechanism of Inhibition of COX-2 Oxygenation of Arachidonic Acid and 2-Arachidonoylglycerol by Ibuprofen and Mefenamic Acid

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• 作者：Jeffery J. Prusakiewicz ; Kelsey C. Duggan ; Carol A. Rouzer ; Lawrence J. Marnett
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：August 11, 2009
• 年：2009
• 卷：48
• 期：31
• 页码：7353-7355
• 全文大小：660K
• 年卷期：v.48,no.31(August 11, 2009)
• ISSN：1520-4995

文摘

Ibuprofen and mefenamic acid are weak, competitive inhibitors of cyclooxygenase-2 (COX-2) oxygenation of arachidonic acid (AA) but potent, noncompetitive inhibitors of 2-arachidonoylglycerol (2-AG) oxygenation. The slow, tight-binding inhibitor, indomethacin, is a potent inhibitor of 2-AG and AA oxygenation whereas the rapidly reversible inhibitor, 2′-des-methylindomethacin, is a potent inhibitor of 2-AG oxygenation but a poor inhibitor of AA oxygenation. These observations are consistent with a model in which inhibitors bind in one subunit of COX-2 and inhibit 2-AG binding in the other subunit of the homodimeric protein. In contrast, ibuprofen and mefenamate must bind in both subunits to inhibit AA binding.