Le Gal A, Dréano Y, Gervasi P G, Berthou F
Laboratoire de Biochimie, EA-948, Faculté de Médecine, BP 815, F-29285 Brest Cedex, France.
Toxicol Lett. 2001 Oct 15;124(1-3):47-58. doi: 10.1016/s0378-4274(00)00286-1.
Methyl t-butyl ether (MTBE), ethyl t-butyl ether (ETBE), and t-amyl methyl ether (TAME) are three alkoxyethers added to gasoline to improve combustion and thereby to reduce the level of carbon monoxide and aromatic hydrocarbons in automobile exhaust. Oxidative demethylation of MTBE and TAME and deethylation of ETBE by CYP enzymes results in the formation of tertiary alcohols and aldehydes, both potentially toxic. The metabolism of these three alkoxyethers was studied in a panel of 12 human liver microsomes. The relatively low apparent Km(1) was 0.25+/-0.17 (mean+/-SD), 0.11+/-0.08 and 0.10+/-0.07 mM and the high apparent Km(2) was 2.9+/-1.8, 5.0+/-2.7 and 1.7+/-1.0 mM for MTBE, ETBE and TAME, respectively. Kinetic data, correlation studies, chemical inhibition and metabolism by heterologously expressed human CYPs support the assertion that the major enzyme involved in MTBE, ETBE and TAME metabolisms is CYP2A6, with a minor contribution of CYP3A4 at low substrate concentration.
甲基叔丁基醚（MTBE）、乙基叔丁基醚（ETBE）和叔戊基甲基醚（TAME）是三种添加到汽油中以改善燃烧从而降低汽车尾气中一氧化碳和芳烃水平的烷氧基醚。细胞色素P450（CYP）酶对MTBE和TAME的氧化脱甲基作用以及对ETBE的脱乙基作用会导致生成叔醇和醛，二者都可能具有毒性。在一组12个人类肝微粒体中研究了这三种烷氧基醚的代谢情况。MTBE、ETBE和TAME的相对低表观米氏常数（Km(1)）分别为0.25±0.17（平均值±标准差）、0.11±0.08和0.10±0.07 mM，高表观米氏常数（Km(2)）分别为2.9±1.8、5.0±2.7和1.7±1.0 mM。动力学数据、相关性研究、化学抑制以及异源表达的人类细胞色素P450的代谢情况均支持以下观点：参与MTBE、ETBE和TAME代谢的主要酶是CYP2A6，在低底物浓度时CYP3A4有较小贡献。
