Interaction of PGBx and peroxides with cytochrome c and inhibition of lipid peroxidation.
PGBx, a derivative of prostaglandin B1, stimulated the oxidation of cytochrome c in the presence of H2O2. Although the reaction was nonenzymatic, the apparent activation energies of 12 and 4.9 kcal above and below the transition at 21.5 degrees C were similar to those for oxidation by cytochrome oxidase. Depletion of H2O2 and oxidation of cytochrome c followed similar time courses, suggesting that H2O2 was consumed in the reaction. PGBx was a specific requirement, but organic hydroperoxides (ethyl and T-butyl) could replace H2O2. Low concentrations of ethyl or t-butyl hydroperoxide initially stimulated the oxidation of cytochrome c; this stimulation disappeared before completion of the oxidation, but was restored when the hydroperoxide concentration was renewed, suggesting that these hydroperoxides were probably also consumed in the reaction. The concentration of PGBx (8.9 microM) required for half-maximum stimulation of the oxidation was similar to the apparent Kd for its dissociation from oxidized cytochrome c (6.8 microM). Binding data and CD spectra suggested that a 1:1 complex between cytochrome c and PGBx was formed, altering the conformation of the heme region. This conformational change caused a shift of the Soret absorption peak from 410 to 406 nm and may be responsible for the enhanced oxidizability of the cytochrome c by H2O2. Cytochrome c inhibited lipid peroxidation in microsomes, an effect enhanced by the addition of PGBx. In the absence of lipid peroxidation, cytochrome c and PGBx stimulated NADPH oxidation via NADPH-cytochrome c reductase. Thus the inhibition of lipid peroxidation by cytochrome c and PGBx may involve either the removal of hydroperoxides or deviation of electron transfer away from the pathway for lipid peroxidation.
D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism*; D006736:Horses; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis*; D009206:Myocardium / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D011456:Prostaglandins B / Q000494:pharmacology*; D013696:Temperature; D020122:tert-Butylhydroperoxide
D003574:Cytochrome c Group; D008054:Lipid Peroxides; D010545:Peroxides; D011108:Polymers; D011453:Prostaglandins; D011456:Prostaglandins B; C025577:ethyl hydroperoxide; C024303:prostaglandin Bx; D009249:NADP; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide