Biomaterial Database

Oxidation of phenidone and BW755C by prostaglandin endoperoxide synthetase. 1982

L J Marnett, and P H Siedlik, and L W Fung

1-Phenyl-3-pyrazolidone (phenidone) and 3-amino-1-(m-(trifluoromethyl)-phenyl)-2-pyrazoline (BW755C) are oxidized by the hydroperoxidase component of prostaglandin endoperoxide synthetase and by horseradish peroxidase. The initial oxidation products are radical cations which exhibit visible absorption maxima at 514, 490, and 472 nm (phenidone) and 535, 500, and 488 nm (BW755C). The radical cation of phenidone can be detected by electron paramagnetic resonance spectroscopy as a complex multiline signal centered at g = 2.0039. In addition to being oxidized by peroxidases both compounds are cofactors for the reduction of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid to 15-hydroxy-5,8,11,13-eicosatetraenoic acid by the hydroperoxidase activity of purified and hematin-reconstituted prostaglandin endoperoxide synthetase. As a consequence of their oxidation by prostaglandin endoperoxide synthetase, phenidone and BW755C inhibit the hydroperoxide-dependent oxidation of phenylbutazone, luminol, diphenylisobenzofuran, epinephrine, and guaiacol by ram seminal vesicle microsomes. The inhibition of phenylbutazone oxidation is competitive and exhibits Ki values of 16 microM (BW755C) and 45 microM (phenidone). BW755C and phenidone stimulate prostaglandin biosynthesis by purified and reconstituted prostaglandin endoperoxide synthetase at concentrations up to 100 microM but inhibit at higher concentrations (I50 values approximately 210 microM and 1180 microM, respectively). The ability of phenidone and BW755C to act as peroxidase reducing cofactors or radical scavengers may contribute to their observed biochemical and pharmacological effects.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D011451	Prostaglandin-Endoperoxide Synthases	Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.	Fatty Acid Cyclo-Oxygenase,PGH Synthase,Prostaglandin H Synthase,Prostaglandin Synthase,Prostaglandin-Endoperoxide Synthase,Arachidonic Acid Cyclooxygenase,Cyclo-Oxygenase,Cyclooxygenase,Cyclooxygenases,Hydroperoxide Cyclase,PGH2 Synthetase,Prostaglandin Cyclo-Oxygenase,Prostaglandin Cyclooxygenase,Prostaglandin Endoperoxide Synthetase,Prostaglandin G-H Synthase,Prostaglandin H2 Synthetase,Prostaglandin Synthetase,Cyclase, Hydroperoxide,Cyclo Oxygenase,Cyclo-Oxygenase, Fatty Acid,Cyclo-Oxygenase, Prostaglandin,Cyclooxygenase, Arachidonic Acid,Cyclooxygenase, Prostaglandin,Endoperoxide Synthetase, Prostaglandin,Fatty Acid Cyclo Oxygenase,G-H Synthase, Prostaglandin,Prostaglandin Cyclo Oxygenase,Prostaglandin Endoperoxide Synthases,Prostaglandin G H Synthase,Synthase, PGH,Synthase, Prostaglandin,Synthase, Prostaglandin G-H,Synthase, Prostaglandin H,Synthase, Prostaglandin-Endoperoxide,Synthases, Prostaglandin-Endoperoxide,Synthetase, PGH2,Synthetase, Prostaglandin,Synthetase, Prostaglandin Endoperoxide,Synthetase, Prostaglandin H2
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012669	Seminal Vesicles	A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Seminal Vesicle,Vesicle, Seminal,Vesicles, Seminal
D012756	Sheep	Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.	Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D013053	Spectrophotometry	The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities