过氧化氢与血红素在微粒体脂质过氧化中的作用

Hydrogen peroxide and hematin in microsomal lipid peroxidation.

作者信息

Ursini F, Maiorino M, Ferri L, Valente M, Gregolin C

出版信息

J Inorg Biochem. 1981 Oct;15(2):163-9. doi: 10.1016/s0162-0134(00)80300-1.

Abstract

Lipids of rat liver microsomes underwent peroxidation with production of malondialdehyde in the presence of H2O2 and hematin. Rates of peroxidation of 27-33 nmol of MDA formed/mg of microsomal protein/30 min were measured with 5 mM H2O2 and 10 microM hematin at 22 degrees C. Histidine (0.01 M) caused a 55% inhibition. Hematin could be added to the reaction mixtures either simultaneously with H2O2 or afterwards, when all H2O2 had been destroyed by catalase present in the microsomal preparation. Catalase was necessary for formation of MDA. Indeed, when heat-denatured microsomes were employed, incubation with H2O2 and the iron complex led to formation of lipid hydroperoxides; however, no production of MDA was observed, unless exogenous catalase was added together with H2O2 and hematin to the reaction mixture. The role of H2O2 in microsomal lipid peroxidation is that of promoting the formation of fatty acid hydroperoxides. These are decomposed in the presence of hematin, with formation of free radicals, bicyclic endoperoxides and MDA. Catalase is necessary to remove H2O2, which, after starting the peroxidation process, blocks the decomposition of lipid hydroperoxides, apparently by binding to the iron complex.

摘要

在过氧化氢（H₂O₂）和血红素存在的情况下，大鼠肝脏微粒体的脂质会发生过氧化反应，生成丙二醛。在22℃下，用5 mM H₂O₂和10 μM血红素测定过氧化速率，即每毫克微粒体蛋白在30分钟内形成27 - 33 nmol丙二醛。组氨酸（0.01 M）可产生55%的抑制作用。血红素可以与H₂O₂同时加入反应混合物中，也可以在所有H₂O₂被微粒体制剂中存在的过氧化氢酶破坏后加入。过氧化氢酶对于丙二醛的形成是必需的。实际上，当使用热变性的微粒体时，与H₂O₂和铁络合物一起孵育会导致脂质氢过氧化物的形成；然而，除非将外源性过氧化氢酶与H₂O₂和血红素一起加入反应混合物中，否则不会观察到丙二醛的产生。H₂O₂在微粒体脂质过氧化中的作用是促进脂肪酸氢过氧化物的形成。这些在血红素存在下分解，形成自由基、双环内过氧化物和丙二醛。过氧化氢酶对于去除H₂O₂是必需的，H₂O₂在启动过氧化过程后，显然通过与铁络合物结合来阻止脂质氢过氧化物的分解。