Lack of covalent modification of prostaglandin synthetase (cyclo-oxygenase) by indomethacin.
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.
D000107:Acetylation; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D004357:Drug Synergism; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects
D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin