PEROXIDATIC OXIDATION OF BENZO[A]PYRENE AND PROSTAGLANDIN BIOSYNTHESIS

The arachidonic acid dependent oxidation of benzo[α]pyrene to a mixture of 3, 6-, 1, 6-, and 6, 12-quinones has been studied by using enzyme preparations from sheep seminal vesicles. Maximal oxidation is observed at 100 benzo[α]pyrene and 150 μM arachidonic acid. The arachidonic acid dependent oxidation is peroxidatic and utilizes prostaglandin G2 (PGG2), generated in situ from arachidonate, as the hydroperoxide substrate. 15-Hydroperoxy-5, 8, 11, 13-eicosatetraenoic acid is equivalent to PGG2 as a hydroperoxide substrate, but hydrogen peroxide, cumene hydroperoxide, and tert-butyl hydroperoxide are much poorer substrates. Arachidonic acid dependent benzo[α]pyrene oxidation by microsomal and solubilized enzyme preparations is markedly stimulated by a variety of hemes and heme proteins. This is not due to the previously reported heme stimulation of prostaglandin biosynthesis [Yoshimoto, A., Ito, H., & Tomita, K. (1970) J. Biochem. (Tokyo) 68, 487-499], Instead, the hemes function directly as peroxidases utilizing fatty acid hydroperoxides as substrates. The incubation of PGG2 with commercial methemoglobin in the absence of any other protein gives rise to significant benzo[α]pyrene oxidation to quinones. The widespread occurrence of heme proteins in animal tissue suggests that the peroxidatic oxidation of benzo[α]pyrene will be significant in any tissue that makes appreciable concentrations of fatty acid hydroperoxides. © 1979, American Chemical Society. All rights reserved.