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  • Title: Lack of covalent modification of prostaglandin synthetase (cyclo-oxygenase) by indomethacin.
    Author: Stanford N, Roth GJ, Shen TY, Majerus PW.
    Journal: Prostaglandins; 1977 Apr; 13(4):669-75. PubMed ID: 404672.
    Abstract:
    We have previously shown that aspirin irreversibly inhibits prostaglandin synthetase (cyclo-oxygenase) by acetylating the active site of the enzyme. By utilizing 14C-labeled indomethacin and a close analogue, we now show that indomethacin, unlike aspirin, does not covalently modify cyclo-oxygenase. Furthermore, indomethacin binding to the enzyme may be reversible since even though indomethacin can inhibit acetylation by aspirin, when enzyme inhibited by indomethacin (1 micronM) is treated with 200 micronM aspirin 3 times for 1 hour each, complete acetylation of cyclo-oxygenase is achieved.
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