Hepatic microsomal dealkylations. Inhibition by a tyrosine-copper (II) complex provided with superoxide dismutase activity.

The effect of a divalent copper-tyrosine complex has been evaluated in rat liver microsome-catalyzed dealkylations. The copper complex, which is provided with superoxide dismutase activity, inhibits at micromolar concentrations aminopyrine, p-nitroanisol, and 7-ethoxycoumarin dealkylations. It has also been found that cumene hydroperoxide-supported p-nitroanisol demethylation, the formation of a 440 nm species, and the formation of superoxide radicals are inhibited by the divalent copper complex. On the other hand, 3-chloroperbenzoic acid has been found to support a copper complex-insensitive 7-ethoxycoumarin dealkylation. Oxygen uptake by rat liver microsomes is also inhibited by the copper complex. The data support the concept that the copper complex acts as a superoxide dismutase at the level of a cytochrome P-450 intermediate species, liganded with superoxide anions.