Original Contribution A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H 2 O 2 in Cells and Thereby Their Biological State

Original Contribution A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H 2 O 2 in Cells and Thereby Their Biological State
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原创贡献新范式:锰超氧化物歧化酶影响细胞中 H 2 O 2 的产生及其生物状态

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发表时间:
2006
期刊:
影响因子:
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通讯作者:
Freya Q. Schafer
Freya Q. Schafer
中科院分区:
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文献类型:
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作者:
G. Buettner;Chin F. Ng;Min Wang;Freya Q. Schafer

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线粒体中过氧化氢的主要来源被认为是通过锰超氧化物歧化酶(MnSOD)歧化超氧化物。然而,SOD对H2 O2的细胞产生的作用的性质并没有得到广泛的认识。目前的范例是,SOD的存在导致较低水平的H2 O2,因为它会阻止形成H2 O2的超氧化物的非酶促反应。这项工作的目标是:a)证明SOD可以增加H2 O2的通量,和B)使用动力学模型来确定什么样的动力学和热力学条件导致SOD增加H2 O2的通量。我们研究了两种生物来源的超氧化物生产(黄嘌呤氧化酶和辅酶Q半醌,辅酶Q U-),具有不同的热力学和动力学性质。我们发现,SOD可以改变H2 O2的形成速率的情况下,平衡特异性反应形成超氧化物的平衡常数(K)小于1。一个例子是通过泛半醌自由基与分子氧反应在线粒体的电子传递链(ETC)中形成超氧化物。我们测量了从具有不同水平的MnSOD的细胞释放到培养基中的H2 O2的速率。我们发现,SOD水平越高,H2 O2的积累速率越大。动力学模型的结果与此一致
The principal source of hydrogen peroxide in mitochondria is thought to be from the dismutation of superoxide via the enzyme manganese superoxide dismutase (MnSOD). However, the nature of the effect of SOD on the cellular production of H2O2 is not widely appreciated. The current paradigm is that the presence of SOD results in a lower level of H2O2 because it would prevent the non-enzymatic reactions of superoxide that form H2O2. The goal of this work was to: a) demonstrate that SOD can increase the flux of H2O2, and b) use kinetic modelling to determine what kinetic and thermodynamic conditions result in SOD increasing the flux of H2O2. We examined two biological sources of superoxide production (xanthine oxidase and coenzyme Q semiquinone, CoQ U– ) that have different thermodynamic and kinetic properties. We found that SOD could change the rate of formation of H2O2 in cases where equilibrium-specific reactions form superoxide with an equilibrium constant (K) less than 1. An example is the formation of superoxide in the electron transport chain (ETC) of the mitochondria by the reaction of ubisemiquinone radical with dioxygen. We measured the rate of release of H2O2 into culture medium from cells with differing levels of MnSOD. We found that the higher the level of SOD, the greater the rate of accumulation of H2O2. Results with kinetic modelling were consistent with this
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