Intimate relation between cyclooxygenase and peroxidase activities of prostaglandin H synthase. Peroxidase reaction of ferulic acid and its influence on the reaction of arachidonic acid. [Erratum to document cited in CA121:3808]

Biochemistry ◽  
1994 ◽  
Vol 33 (37) ◽  
pp. 11404-11404
Author(s):  
Marica Bakovic ◽  
H. Brian Dunford
Keyword(s):  
Arachidonic Acid ◽  
Ferulic Acid ◽  
Prostaglandin H Synthase ◽  
Peroxidase Reaction ◽  
Intimate Relation ◽  
Prostaglandin H

Ibuprofen protects human endothelial cell prostaglandin H synthase from hydrogen peroxide

1996 ◽  
Vol 271 (6) ◽  
pp. C1879-C1886 ◽  
Author(s):  
D. A. Wessels ◽  
S. L. Hempel
Keyword(s):  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Endothelial Cell ◽  
Arachidonic Acid Release ◽  
Human Endothelial Cells ◽  
Prostaglandin H Synthase ◽  
Cyclooxygenase Activity ◽  
Acid Release ◽  
Prostaglandin H

Human endothelial cells exposed to H2O2 demonstrate decreased prostacyclin (PGI2) synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We tested the hypothesis that PGH synthase activity could be protected from H2O2 by a reversible nonsteroidal anti-inflammatory drug. Experiments demonstrate that ibuprofen if present during H2O2 exposure, protects endothelial cell PGH synthase against the decrease in prostaglandin formation caused by H2O2. Additional studies demonstrated that decreasing arachidonic acid release from cell phospholipids during H2O2 exposure did not protect PGI2 synthesis following H2O2 exposure. In other experiments, ibuprofen did not chelate Fe2+ in a conformation that inhibited the reactivity of Fe2+. In addition, ibuprofen did not scavenge HO. However, we demonstrate that ibuprofen significantly protects purified PGH synthase cyclooxygenase activity from the effects of H2O2. The results confirm the hypothesis. These findings suggest that ibuprofen displaces oxidant species from the cyclooxygenase site of PGH synthase, thereby preventing oxidation of the functional groups important for PGH synthase activity.

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

1988 ◽  
Vol 66 (12) ◽  
pp. 1524-1530 ◽  
Author(s):  
P. J. Formosa ◽  
T. M. Bray ◽  
S. Kubow
Keyword(s):  
Arachidonic Acid ◽  
Co Oxidation ◽  
Metabolic Activation ◽  
Alternative Mechanism ◽  
Prostaglandin H Synthase ◽  
Initial Event ◽  
Esr Spin Trapping ◽  
Selective Lesion ◽  
Rate Of Oxygen Consumption ◽  
Prostaglandin H

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.

Determination of Arachidonic Acid Based on the Prostaglandin H Synthase Catalyzed Reaction

2000 ◽  
Vol 88 (1-3) ◽  
pp. 033-044 ◽  
Author(s):  
Anna D Ilyina ◽  
José L Martínez Hernández ◽  
César Estrada Badillo ◽  
María G Sena Maldonado ◽  
Sara Carrillo Galindo ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Prostaglandin H Synthase ◽  
Prostaglandin H

Study on N-Demethylation of N,N-Dimethyl-4-aminoazobenzene and N-Nitrosamines by Prostaglandin H Synthase

1997 ◽  
Vol 62 (6) ◽  
pp. 971-980 ◽  
Author(s):  
Marie Stiborová ◽  
Eva Frei ◽  
Heinz H. Schmeiser
Keyword(s):  
Hydrogen Peroxide ◽  
Arachidonic Acid ◽  
Free Radicals ◽  
Seminal Vesicle ◽  
Oxidation Mechanism ◽  
Maximal Velocity ◽  
Prostaglandin H Synthase ◽  
Michaelis Constant ◽  
Prostaglandin H

The in vitro enzymatic metabolism of carcinogenic N,N-dimethyl-4-aminoazobenzene, N-nitroso-N-methylaniline and N-nitroso-N,N-dimethylamine was investigated using ram seminal vesicle microsomal prostaglandin H synthase. Both N-nitrosamines are not converted by the studied enzyme. Formaldehyde is produced by the prostaglandin H synthase catalyzed reaction from N,N-dimethyl-4-aminoazobenzene. Arachidonic acid and hydrogen peroxide serve as cofactors for the oxidation of N,N-dimethyl-4-aminoazobenzene. The apparent Michaelis constant and the maximal velocity values for N,N-dimethyl-4-aminoazobenzene as a substrate are 64 μmol/l and 51.2 nmol HCHO/min/mg protein, respectively. In addition to formaldehyde, N-methyl-4-aminoazobenzene and 4-aminoazobenzene, two unknown substances are the products of the N,N-dimethyl-4-aminoazobenzene oxidation. The oxidation of N,N-dimethyl-4-aminoazobenzene catalyzed by prostaglandin H synthase is inhibited by glutathione, ascorbate and NADH. The results suggest that prostaglandin H synthase metabolizes N,N-dimethyl-4-aminoazobenzene through a one-electron oxidation mechanism, giving rise to free radicals.

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