title: Effect of Trolox C on the oxygenation reaction of prostaglandin endoperoxide synthase with cis,cis-eicosa-11, 14-dienoic acid.
abstract: Trolox C, a water-soluble derivative of alpha-tocopherol, stimulates the oxygenation of cis,cis-eicosa-11, 14-dienoic acid (AH) by prostaglandin endoperoxide synthase at lower concentrations and suppresses the stimulated reaction at higher concentrations. Surprisingly, Trolox C does not affect the stoichiometric ratio between the rate of formation of the oxygenation product 11-hydroxy-12-trans, 14-cis-eicosadienoic acid (AOH) and the rate of disappearance of molecular oxygen. The ratio of the two rates, d[AOH]/-d[O2], remains constant at 2/1 for a series of Trolox C concentrations and in the absence of Trolox C. Results indicate that AH reacts preferentially with Compound I of the enzyme and that Trolox C does not compete for Compound I. Enzyme inactivation begins with formation of an unproductive Compound I-tyrosyl radical (Compound I-X.) which has the same number of oxidizing equivalents as the conventional peroxidase Compound I. The stimulating effect of low concentrations of Trolox C can be explained by reduction of the oxyferryl heme so that Compound I-X. is reduced to a Compound II-X.species, the Compound II analog of Compound I-X.. Thus heme bleaching is prevented. A further one-electron reduction by Trolox C of Compound II-X. reforms the native enzyme, which permits enzyme recycling. Large concentrations of Trolox C inhibit reformation of native enzyme, reducing the extent of stimulation.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bakovic
authors.forename: H B
authors.initials: HB
authors.lastname: Dunford
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002839:Chromans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004537:Eicosanoic Acids / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism; D009195:Peroxidase / Q000737:chemistry / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002839:Chromans; D004537:Eicosanoic Acids; D005227:Fatty Acids; D005609:Free Radicals; C015876:eicosa-11,14-dienoic acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D010105:Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D010100:Oxygen