کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1911397 | 1046815 | 2006 | 13 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H2O2 in Cells and Thereby Their Biological State A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H2O2 in Cells and Thereby Their Biological State](/preview/png/1911397.png)
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–) 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 observation; the steady-state level of H2O2 increases if K < 1, for example CoQ–+O2→CoQ+O2–. However, when K > 1, e.g. xanthine oxidase forming O2–, SOD does not affect the steady state-level of H2O2. Thus, the current paradigm that SOD will lower the flux of H2O2 does not hold for the ETC. These observations indicate that MnSOD contributes to the flux of H2O2 in cells and thereby is involved in establishing the cellular redox environment and thus the biological state of the cell.
Journal: Free Radical Biology and Medicine - Volume 41, Issue 8, 15 October 2006, Pages 1338–1350