The major pitfall encountered with the study of R-propranolol metabolism of a purified cytochrome P-450 system was the destruction of 4-hydroxypropranolol formed during the incubation. The plausible cause of this distinction is primarily due to the production of superoxide ions and hydrogen peroxide in the incubation media of reconstituted system. The combined presence of catalase and superoxide dismutase blocked not only the destruction of 4-hydroxypropranolol (4-OHP) but also the increased rate of desisopropylpropranolol (DIP). Consequently, the DIP/50H and 40HP/5-OH ratios obtained with reconstituted systems containing purified cytochrome P-450 supplemented with superoxide dismutase and catalase approached the ratios obtained with intact microsomes. This observation indicates that extrapolating data obtained by the reconstituted systems to intact microsomes should be made with caution.
