Retinoic Acid 5, 6-Epoxidation by Hemoproteins

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Retinoic acid 5, 6-epoxidase activity was found in several hemoproteins such as human oxy- and methemoglobin (HbO₂ and MetHb), equine skeletal muscle oxy and metmyoglobin (MbO₂ and MetMb), bovine liver catalase, and horseradish peroxidase. Hematin also catalyzed retinoic acid 5, 6-epoxidation. The results suggest that the heme moiety participates in the epoxidation. However, neither horse heart cytochrome c, nor free ferrous ion nor free ferric ion exhibited the epoxidase activity.
Some hemoproteins (HbO₂, MetHb, MbO₂, MetMb, catalase, peroxidase, and hematin) exhibited characteristic individual pH dependences of the activity, suggesting that the epoxidase activities of the hemoproteins are influenced by the apoenzymes to some degree. This view is also supported by the finding that preincubation of an HbO₂ preparation at various temperatures (37-70°C) reduced its epoxidaseactivity with increasing temperature, whereas the activity of hematin was unaffected.
Active oxygen scavengers such as mannitol, catalase, and superoxide dismutase exhibited no effect on the epoxidase activities of HbO₂, MetHb, MbO₂, and MetMb. A ligand of heme, CN-(100 mM), inhibited the epoxidase activities but N₃-(100 mM) did not. The epoxidase activities were completely inhibited by NADPH, NADH, and/or 2-mercaptoethanol but not by NADP⁺ and/or NAD⁺. An intermediatein the epoxidation may be reduced by NADPH, NADH and/or 2-mercaptoethanol. Radical species can be considered as plausible candidates for the intermediate.