Veith Alex, Moorthy Bhagavatula
Interdepartmental Program in Translational Biology and Molecular Medicine, Houston, TX, 77030, USA.
Department of Pediatrics-Newborn, Baylor College of Medicine, Houston, TX, 77030, USA.
Curr Opin Toxicol. 2018 Feb;7:44-51. doi: 10.1016/j.cotox.2017.10.003. Epub 2017 Oct 12.
The cytochrome P450 (CYP) enzymes are a diverse group of heme monooxygenases that, through the course of their reaction cycle, contribute to cellular reactive oxygen species (ROS). CYP enzymes play a crucial role in human physiology and are involved in drug and xenobiotic metabolism as well as biosynthesis of endogenous molecules and are expressed throughout the human body. However, during the course of the CYP catalytic cycle, ROS can be generated through uncoupling of the enzymatic cycle. ROS is known to modify endogenous molecules, included lipids, proteins, and nucleic acids, which can lead to cell damage and death and contribute to disease development. ROS has been implicated in a wide range of diseases and conditions, including cancer and ageing, but ROS also play a role in the normal physiological functions in the cell. Here, we discuss specific examples whereby ROS generated by CYPs contribute to or protect against various phenomena, such as hyperoxic lung injury, oxidative hepatic toxicity, formation of DNA adducts from lipid peroxidation products. We have also discussed the mechanistic roles of CYP enzymes belonging to various families, and their effect on cellular ROS production, in relation to normal cellular function as well as disease pathophysiology.
细胞色素P450（CYP）酶是一类多样的血红素单加氧酶，在其反应循环过程中会产生细胞活性氧（ROS）。CYP酶在人体生理过程中起着至关重要的作用，参与药物和外源性物质的代谢以及内源性分子的生物合成，并且在人体全身都有表达。然而，在CYP催化循环过程中，酶循环的解偶联可产生ROS。已知ROS会修饰内源性分子，包括脂质、蛋白质和核酸，这可能导致细胞损伤和死亡，并促进疾病发展。ROS与多种疾病和病症有关，包括癌症和衰老，但ROS在细胞的正常生理功能中也发挥作用。在这里，我们讨论一些具体例子，即CYPs产生的ROS如何促成或预防各种现象，如高氧性肺损伤、氧化性肝毒性、脂质过氧化产物形成DNA加合物。我们还讨论了属于不同家族的CYP酶的机制作用，以及它们对细胞ROS产生的影响，这与正常细胞功能以及疾病病理生理学有关。
