Hematin-catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by polyunsaturated fatty acid hydroperoxides.
Hematin catalyzes the epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) by 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid and other fatty acid hydroperoxides in the presence of detergent. The major oxidation product is the anti-dihydrodiolepoxide and the minor product is the syn-dihydrodiolepoxide. (+)-BP-7,8-diol is oxidized to (-)-anti-diolepoxide and (+)-syn-diolepoxide whereas (-)-BP-7,8-diol is oxidized to (+)-anti-diolepoxide and (-)-syn-diolepoxide. Oxygen labeling studies indicate that the source of the epoxide oxygen is O2. The phenolic antioxidants butylated hydroxyanisole and butylated hydroxytoluene inhibit epoxidation by 100 and 93%, respectively. These observations suggest that hematin-catalyzed epoxidation proceeds by a free radical mechanism. Incubation of hematin, BP-7,8-diol, and a series of fatty acid hydroperoxides containing two, one, or zero double bonds alpha to the carbon bearing the hydroperoxide indicates that at least one double bond is essential for generation of the epoxidizing agent. Taken with results of the study of the metabolism of 13-hydroperoxy-9-cis,11-trans-octadecadienoic acid by hematin described in the accompanying paper (Dix, T. A., and Marnett, L. J. (1985) J. Biol. Chem. 260, 5351-5357), these results indicate that the epoxidizing agent is a peroxyl radical generated by coupling of O2 to a carbon-centered radical derived from the double bonds adjacent to the hydroperoxide group. The detergents Tween 20, Triton X-100, and Triton X-405 dramatically enhance epoxidation above but not below their critical micellar concentrations. The intensity and lambda max of the ultraviolet absorption spectrum of BP-7,8-diol increase in the presence of detergent, indicating that an important role of detergent is solubilization of the hydrophobic substrate. However, detergent also stimulates the hematin-catalyzed oxidation of a water-soluble polycyclic hydrocarbon, bis-(carboxyethyl)-anthracene, suggesting that detergent has an effect on the peroxidase activity of hematin. A detailed mechanism for epoxidation of BP-7,8-diol by hematin and fatty acid hydroperoxides is presented and its relevance to other hydroperoxide-dependent epoxidizing systems is discussed.
D001580:Benzopyrenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004101:Dihydroxydihydrobenzopyrenes; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000378:metabolism*; D008041:Linoleic Acids / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D017830:Octoxynol; D011092:Polyethylene Glycols
D001580:Benzopyrenes; D004101:Dihydroxydihydrobenzopyrenes; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008054:Lipid Peroxides; C017228:benzo(a)pyrene 7,8-dihydrodiol; C008285:linoleic acid hydroperoxide; D011092:Polyethylene Glycols; D006418:Heme; D006427:Hemin; D017830:Octoxynol