Department of Biochemistry, Vanderbilt University School of Medicine, 638 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA.
Chem Biol Interact. 2020 May 1;322:109056. doi: 10.1016/j.cbi.2020.109056. Epub 2020 Mar 18.
Cytochrome P450 (P450) 2E1 is the major P450 enzyme involved in ethanol metabolism. That role is shared with two other enzymes that oxidize ethanol, alcohol dehydrogenase and catalase. P450 2E1 is also involved in the bioactivation of a number of low molecular weight cancer suspects, as validated in vivo in mouse models where cancers could be attenuated by deletion of Cyp2e1. P450 2E1 does not have a role in global production of reactive oxygen species but localized roles are possible, e.g. in mitochondria. The structures, conformations, and catalytic mechanisms of P450 2E1 have some unusual features among P450s. The concentration of hepatic P450 varies ≥10-fold among humans, possibly in part due to single nucleotide variants. The level of P450 2E1 may have relevance in the rates of oxidation of drugs, particularly acetaminophen and anesthetics.
细胞色素 P450（P450）2E1 是参与乙醇代谢的主要 P450 酶。这一作用与另外两种氧化乙醇的酶——乙醇脱氢酶和过氧化氢酶共享。P450 2E1 还参与了许多低分子量癌症可疑物的生物活化，在小鼠模型中得到了体内验证，在这些模型中，通过删除 Cyp2e1 可以减弱癌症。P450 2E1 在活性氧的全球产生中没有作用，但可能存在局部作用，例如在线粒体中。P450 2E1 的结构、构象和催化机制在 P450 中具有一些不寻常的特征。肝 P450 的浓度在人类中变化≥10 倍，可能部分是由于单核苷酸变异。P450 2E1 的水平可能与药物氧化的速度有关，特别是对乙酰氨基酚和麻醉剂。
