Wendel A, Hallbach J
Biochem Pharmacol. 1986 Feb 1;35(3):385-9. doi: 10.1016/0006-2952(86)90209-1.
Phospholipids were quantitatively extracted from microsomes and separated by an h.p.l.c. gradient system with a solvent mixture of n-hexane/n-propanol/water/acetic acid. In a model reaction using horseradish peroxidase/H2O2 in order to activate acetaminophen and inactivated microsomes as target, a covalent binding of 10 nmol drug metabolite per mg microsomal lipid was found. In isolated intact microsomes from methylcholanthrene-pretreated male albino mice, a binding of 0.1 nmol acetaminophen metabolite per mg phospholipid was determined while the binding of metabolites to protein amounted to 3 nmol/mg. The results demonstrate that in mouse liver microsomes metabolizing acetaminophen, about one out of 10(4) phospholipid molecules is modified.
从微粒体中定量提取磷脂，并用正己烷/正丙醇/水/乙酸的溶剂混合物通过高效液相色谱梯度系统进行分离。在一个使用辣根过氧化物酶/H₂O₂来活化对乙酰氨基酚并将失活的微粒体作为靶标的模型反应中，发现每毫克微粒体脂质有10纳摩尔药物代谢物的共价结合。在用甲基胆蒽预处理的雄性白化小鼠的分离完整微粒体中，测定出每毫克磷脂有0.1纳摩尔对乙酰氨基酚代谢物的结合，而代谢物与蛋白质的结合量为3纳摩尔/毫克。结果表明，在代谢对乙酰氨基酚的小鼠肝微粒体中，约每10⁴个磷脂分子中有一个被修饰。
