Heinemeyer G, Hildebrandt A G, Roots I, Lehne L, Nigam S
Arch Toxicol Suppl. 1979(2):491-6. doi: 10.1007/978-3-642-67265-1_62.
"Uncoupling" of microsomal hepatic oxygenases is characterized by a situation in which microsomal monooxygenases exhibit more oxidase than oxygenase activity with an increased formation of hydrogen peroxide at the expense of O2, NADPH and substrate hydroxylation. The importance of such in vitro observations with respect to physiological conditions "in vivo" has been tested by investigating elimination kinetics of ethanol. If hexobarbital, a substrate of mixed function oxygenase as well as an "uncoupler", is given to guinea pigs together with ethanol, changes in the elimination of ethanol occur. It is suggested that this is the consequence of an increased formation of H2O2 which contributes via peroxidatic reaction of catalase to the elimination of ethanol. The results also show additional interactions of hexobarbital as well as of ethylmorphine with ethanol elimination. Both compounds increased the initial blood levels of ethanol which precede accelerated elimination, probably by a first pass effect. At low concentrations of ethanol, ethylmorphine inhibits ethanol elimination by inhibition of ADH.
微粒体肝氧化酶的“解偶联”表现为这样一种情况：微粒体单加氧酶表现出的氧化酶活性多于加氧酶活性，过氧化氢生成增加，同时氧气、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）和底物羟基化减少。通过研究乙醇的消除动力学，测试了这种体外观察结果对于“体内”生理状况的重要性。如果将作为混合功能氧化酶底物以及“解偶联剂”的己巴比妥与乙醇一起给予豚鼠，乙醇的消除会发生变化。有人认为，这是过氧化氢生成增加的结果，过氧化氢通过过氧化氢酶的过氧化物酶反应促进乙醇的消除。结果还显示了己巴比妥以及乙基吗啡与乙醇消除之间的其他相互作用。这两种化合物都增加了乙醇消除加速之前的初始血液水平，可能是通过首过效应。在低浓度乙醇时，乙基吗啡通过抑制乙醇脱氢酶（ADH）来抑制乙醇的消除。
