Optical spectra and kinetics of reactions of prostaglandin H synthase: effects of the substrates 13-hydroperoxyoctadeca-9,11-dienoic acid, arachidonic acid, N,N,N',N'-tetramethyl-p-phenylenediamine, and phenol and of the nonsteroidal anti-inflammatory drugs aspirin, indomethacin, phenylbutazone, and bromfenac.
A combination of cyclooxygenase activity assays, rapid spectrophotometry and pre-steady-state, steady-state, and transient-state kinetics is used to characterize further the properties of prostaglandin H synthase. 13-Hydroperoxyoctadeca-9-11-dienoic acid is used as oxidizing substrate and the effects of the following compounds are examined: arachidonic acid, N,N,N',N'-tetramethyl-p-phenylenediamine, phenol, diethyldithiocarbamate, and the nonsteroidal anti-inflammatory drugs aspirin, indomethacin, phenylbutazone, and Bromfenac. The order of reactivity of four of these substrates, predominantly with compound II of prostaglandin H synthase, is N,N,N',N'-tetramethyl-p-phenylenediamine greater than phenol greater than indomethacin approximately phenylbutazone. Aspirin exhibits no effect. Arachidonic acid causes inactivation. Diethyldithiocarbamate acts as a reducing substrate for the oxidized forms of prostaglandin H synthase. Bromfenac appears to act both as a protective agent and inhibitor.
MacDonald
I D
ID
Department of Chemistry, University of Alberta, Edmonton, Canada.
Graff
G
G
Anderson
L A
LA
Dunford
H B
HB
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D001969:Bromobenzenes / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008041:Linoleic Acids / Q000494:pharmacology; D008054:Lipid Peroxides; D008297:Male; D019800:Phenol; D010636:Phenols / Q000494:pharmacology; D010653:Phenylbutazone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013053:Spectrophotometry; D013772:Tetramethylphenylenediamine / Q000494:pharmacology
D001095:Arachidonic Acids; D001577:Benzophenones; D001969:Bromobenzenes; D008041:Linoleic Acids; D008054:Lipid Peroxides; D010636:Phenols; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D016718:Arachidonic Acid; D019800:Phenol; C053083:bromfenac; D011451:Prostaglandin-Endoperoxide Synthases; D010653:Phenylbutazone; D013772:Tetramethylphenylenediamine; D001241:Aspirin; D007213:Indomethacin