Biomaterial Database

Metabolism of 3-methylindole by prostaglandin H synthase in ram seminal vesicles. 1988

P J Formosa, and T M Bray, and S Kubow

Department of Nutritional Sciences, University of Guelph, Ont., Canada.

3-Methylindole (3MI) causes a highly tissue- and species-selective lesion of the lung. Metabolic activation of 3MI by the NADPH-dependent mixed function oxidase (MFO) system is the initial event in the lung-specific toxicity. One-electron co-oxidation of 3MI by prostaglandin H synthase (PHS) has been implicated as an alternative mechanism for toxicity in the lung that contains high PHS activity. The objective of this study was to determine if 3MI can be co-oxidized by the arachidonic acid dependent PHS complex. Ram seminal vesicle (RSV) microsomes, which lack MFO activity, were used as a source of PHS. Incubations of RSV microsomes with 3MI, at a concentration as low as 0.01 mM, showed an increase in PHS activity, as indicated by an enhanced rate of oxygen consumption. This effect was arachidonic acid dependent and was inhibited (98%) by indomethacin. Addition of 3MI resulted in a concentration-dependent increase in PHS-catalyzed prostaglandin biosynthesis from [14C]arachidonic acid. PHS-dependent oxidative metabolism of [14C]3MI resulted in a twofold increase in ethyl acetate extracted radiolabelled metabolites. ESR spin-trapping studies demonstrated the presence of a 3MI free radical generated from the metabolism of 3MI by horseradish peroxidase, a model system of PHS hydroperoxidase. The results indicate that 3MI can be co-oxidized by the arachidonic acid-dependent PHS complex. Co-oxidation of 3MI by PHS may play a role in the tissue specificity of 3MI-induced pneumotoxicity.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297	Male		Males
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D010101	Oxygen Consumption	The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)	Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
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
D011453	Prostaglandins	A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.	Prostaglandin,Prostanoid,Prostanoids
D004578	Electron Spin Resonance Spectroscopy	A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.	ENDOR,Electron Nuclear Double Resonance,Electron Paramagnetic Resonance,Paramagnetic Resonance,Electron Spin Resonance,Paramagnetic Resonance, Electron,Resonance, Electron Paramagnetic,Resonance, Electron Spin,Resonance, Paramagnetic
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
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
D001095	Arachidonic Acids		Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic