| 10491304 |
Osada M, Ogura Y, Yasui H, Sakurai H: Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations. Carcinogenesis. 1995 Apr;16(4):837-40.
Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1) O (2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN (3)) ((1) O (2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN (3). (1) O (2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1) O (2) was quenched by the additions of beta-carotene, NaN (3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN (3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K (s)). In contrast, (1) O (2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1) O (2) in P450-dependent substrate oxygenations is proposed. |
0(0,0,0,0) |