Estabrook R W, Martin-Wixtrom C, Saeki Y, Renneberg R, Hildebrandt A, Werringloer J
Xenobiotica. 1984 Jan-Feb;14(1-2):87-104. doi: 10.3109/00498258409151400.
Fifteen different secondary and tertiary methyl amines have been examined as substrates for the cytochromes P-450 of rat-liver microsomes to determine the similarities or differences between the NADPH and oxygen-dependent N-demethylation reaction and the reaction occurring in the presence of hydrogen peroxide. No apparent correlation of the rates of formaldehyde formation using the two different conditions of oxidation was observed. The types of cytochromes P-450 were altered by using rat-liver microsomes from animals treated with various inducing agents. No obvious predictable dependence on the animals treated with various inducing agents. No obvious predictable dependence on the type of cytochrome P-450 present was obtained for the hydrogen peroxide-supported peroxidatic reaction. It is concluded that the hydrogen peroxide-dependent N-demethylation reaction occurs by a reaction mechanism distinct from that occurring during the mixed-function oxidase activity of cytochrome P-450 obtained in the presence of NADPH and oxygen.
已对15种不同的仲胺和叔胺作为大鼠肝脏微粒体细胞色素P-450的底物进行了研究，以确定NADPH和氧依赖性N-去甲基化反应与过氧化氢存在下发生的反应之间的异同。未观察到使用两种不同氧化条件时甲醛形成速率的明显相关性。通过使用来自用各种诱导剂处理的动物的大鼠肝脏微粒体，改变了细胞色素P-450的类型。对于过氧化氢支持的过氧化物酶反应，未获得对用各种诱导剂处理的动物的明显可预测依赖性。得出的结论是，过氧化氢依赖性N-去甲基化反应通过与在NADPH和氧存在下获得的细胞色素P-450的混合功能氧化酶活性期间发生的反应不同的反应机制发生。
