Brault D, Neta P, Patterson L K
Chem Biol Interact. 1985 Aug-Sep;54(3):289-97. doi: 10.1016/s0009-2797(85)80170-8.
The toxicity of halogenated alkanes originates from their metabolism by cytochrome P-450 which leads to the formation of reactive intermediates. In particular, peroxyl radicals derived from the halogenated compounds are believed to induce peroxidative chain degradation of lipids. To examine this hypothesis, radical reactions in a system involving FeIII-deuteroporphyrin as a model of cytochrome P-450, fatty acids or cholesterol, and carbon tetrachloride or the anesthetic agent halothane are studied by means of pulse radiolysis. It is shown that haloperoxyl radicals react with the fatty acids in competition with their reaction with the ferriporphyrin. Moreover, the secondary fatty acid peroxyl radicals also react efficiently with the porphyrin. A model for halogenated alkane toxicity is discussed in terms of these new findings. The importance of local oxygen concentration and structural arrangement of fatty acids around cytochrome P-450 are emphasized.
卤代烷烃的毒性源于它们通过细胞色素P - 450进行的代谢，这会导致活性中间体的形成。特别是，卤代化合物衍生的过氧自由基被认为会引发脂质的过氧化链式降解。为了检验这一假设，通过脉冲辐解研究了一个涉及FeIII - 氘代卟啉作为细胞色素P - 450模型、脂肪酸或胆固醇以及四氯化碳或麻醉剂氟烷的体系中的自由基反应。结果表明，卤过氧自由基与脂肪酸反应，同时也与铁卟啉反应。此外，二级脂肪酸过氧自由基也能与卟啉高效反应。根据这些新发现讨论了卤代烷烃毒性的模型。强调了细胞色素P - 450周围局部氧浓度和脂肪酸结构排列的重要性。
