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.
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000818:Animals; D001593:Benzyl Compounds / Q000378:metabolism; D002723:Chlorobenzoates / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D003374:Coumarins / Q000378:metabolism; D003640:Dealkylation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D008956:Models, Chemical; D009575:Nitroanisole O-Demethylase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism*; D014443:Tyrosine / Q000494:pharmacology*
D001593:Benzyl Compounds; D002723:Chlorobenzoates; D003374:Coumarins; D010545:Peroxides; D014443:Tyrosine; D003300:Copper; D006899:Mixed Function Oxygenases; D009575:Nitroanisole O-Demethylase; D013482:Superoxide Dismutase; D000633:Aminopyrine N-Demethylase