Evidence for H2O2 mediating the irreversible action of acetylenic inhibitors of prostaglandin biosynthesis.
Oxidizing intermediates formed during prostaglandin biosynthesis can be detected by ferrocytochrome c and epinephrine. Different intermediates were responsible for the oxidative colorimetric changes with epinephrine and ferrocytochrome c, and submicromolar amounts of oxidant were detectable. Catalase diminished the absorbance change with epinephrine, but it did not stop the conversion of arachidonate to prostaglandins. This result indicates that small amounts of H2O2 were formed when producing the colorimetric change, and these had no apparent effect upon the enzyme stability. No colorimetric changes were detected during the time-dependent loss of oxygenase activity caused by various acetylenic acids, indicating that negligible amounts of H2O2 were formed. Nevertheless, the destructive action of the acetylenic acid was prevented by catalase, and it thereby appeared due to small amounts of H2O2 generated in situ as a result of a metastable complex of enzyme, oxygen and the acetylenic substrate analog.
D000114:Acetylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep
D001095:Arachidonic Acids; D003574:Cytochrome c Group; D005227:Fatty Acids; D011453:Prostaglandins; D006861:Hydrogen Peroxide; D002374:Catalase; D011451:Prostaglandin-Endoperoxide Synthases; D000114:Acetylene; D007213:Indomethacin; D004837:Epinephrine