Hydroperoxide-dependent epoxidation of 3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene by ram seminal vesicle microsomes and by hematin.
Addition of arachidonic acid to ram seminal vesicle microsomes oxidizes 3,4-dihydroxy-3,4-dihydrobenzo[a]anthracene (BA-3,4-diol) to five more polar products. Four of the products are identified by chromatographic and spectroscopic analysis as tetrahydrotetraols, which are solvolysis products of dihydrodiolepoxides. The fifth product is a 10-methyl ether formed by methanolysis of the anti-diolepoxide. Quantitation of the individual products indicates that anti-diolepoxides predominate over syn-diolepoxides by approximately 2:1. Identical product profiles are detected from the reaction of BA-3,4-diol with hematin and 13-hydroperoxy-octadecadienoic acid in the presence of Tween 20. No other products are detected in either system, which indicates that peroxyl radicals oxidize BA-3,4-diol exclusively by epoxidation of the 1,2-double bond. The stereochemical and regiochemical differences between oxidation of BA-3,4-diol by peroxyl radicals and cytochrome P-450 are dramatic and suggest that BA-3,4-diol is uniquely suited as a probe to quantitate peroxyl radical-dependent epoxidation in vitro and in vivo.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D005609:Free Radicals; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D012669:Seminal Vesicles / Q000378:metabolism; D012756:Sheep
D001551:Benz(a)Anthracenes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005609:Free Radicals; D008054:Lipid Peroxides; D002083:Butylated Hydroxyanisole; D006418:Heme; C015149:benzanthracene-3,4-dihydrodiol; D006427:Hemin; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases