Yang E Y, Campbell A, Bondy S C
Center for Occupational and Environmental Health, Department of Community of Environmental Medicine, University of California, Irvine 92697-1820, USA.
Redox Rep. 2000;5(6):371-5. doi: 10.1179/135100000101535942.
Iron catalyzes the production of reactive oxygen species (ROS) through the Fenton reaction. The modification of this phenomenon in the presence of various thiol compounds that are nominally reducing agents has been studied. Using the synaptosomal/mitochondrial (P2) fraction of rat cerebral cortex as a biological source of reactive oxygen species (ROS) production, we studied the influence of four compounds, glutathione (GSH), cysteine, N-acetyl-cysteine (NAC), and homocysteine on iron-induced ROS production. None of the thiol compounds alone, at the concentrations used, affected the basal rate of ROS production in the P2 fraction. GSH, homocysteine and NAC did not alter Fe-induced ROS generation, while cysteine greatly potentiated ROS formation. Measurement of the rate of ROS production in the presence of varying concentrations of cysteine together with 20 microM ferrous iron revealed a dose-response relationship. The mechanism whereby free cysteine, but not the cysteine-containing peptide GSH, homocysteine or NAC with a blocked amino group, exacerbates the pro-oxidant properties of ferrous iron probably involves formation of a complex between iron, a sulfhydryl and a free carboxyl residue located at a critical distance from the -SH group. Cysteine-iron interactions may, in part, account for the excessive toxicity of free cysteine in contrast to GSH and NAC.
铁通过芬顿反应催化活性氧（ROS）的产生。人们已经研究了在各种名义上为还原剂的硫醇化合物存在下这种现象的变化。我们以大鼠大脑皮质的突触体/线粒体（P2）组分作为活性氧（ROS）产生的生物来源，研究了四种化合物，即谷胱甘肽（GSH）、半胱氨酸、N-乙酰半胱氨酸（NAC）和同型半胱氨酸对铁诱导的ROS产生的影响。在所使用的浓度下，单独的硫醇化合物均未影响P2组分中ROS产生的基础速率。GSH、同型半胱氨酸和NAC并未改变铁诱导的ROS生成，而半胱氨酸则极大地增强了ROS的形成。在存在不同浓度半胱氨酸以及20微摩尔亚铁的情况下测量ROS产生速率，结果显示出剂量反应关系。游离半胱氨酸而非含半胱氨酸的肽GSH、同型半胱氨酸或氨基被封闭的NAC加剧亚铁促氧化特性的机制，可能涉及铁、巯基和与-SH基团相距临界距离的游离羧基残基之间形成复合物。与GSH和NAC相比，半胱氨酸与铁的相互作用可能部分解释了游离半胱氨酸的过度毒性。
