Journal article
A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H2O2 in Cells and Thereby Their Biological State
Free radical biology & medicine, Vol.41(8), pp.1338-1350
10/15/2006
DOI: 10.1016/j.freeradbiomed.2006.07.015
PMCID: PMC2443724
PMID: 17015180
Abstract
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 H
2
O
2
is not widely appreciated. The current paradigm is that the presence of SOD results in a lower level of H
2
O
2
because it would prevent the non-enzymatic reactions of superoxide that form H
2
O
2
. The goal of this work was to: a) demonstrate that SOD can increase the flux of H
2
O
2
, and b) use kinetic modelling to determine what kinetic and thermodynamic conditions result in SOD increasing the flux of H
2
O
2
. 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 H
2
O
2
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 H
2
O
2
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 H
2
O
2
. Results with kinetic modelling were consistent with this observation; the steady-state level of H
2
O
2
increases if
K
< 1, for example CoQ
•−
+ O
2
→ CoQ + O
2
•−
. However, when
K
> 1,
e.g.
xanthine oxidase forming O
2
•−
, SOD does not affect the steady state-level of H
2
O
2
. Thus, the current paradigm that SOD will lower the flux of H
2
O
2
does not hold for the ETC. These observations indicate that MnSOD contributes to the flux of H
2
O
2
in cells and thereby is involved in establishing the cellular redox environment and thus the biological state of the cell.
Details
- Title: Subtitle
- A New Paradigm: Manganese Superoxide Dismutase Influences the Production of H2O2 in Cells and Thereby Their Biological State
- Creators
- Garry R Buettner - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242Chin F Ng - Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA 52242Min Wang - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242V.G.J Rodgers - Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA 52242Freya Q Schafer - Free Radical and Radiation Biology Program, The University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.41(8), pp.1338-1350
- DOI
- 10.1016/j.freeradbiomed.2006.07.015
- PMID
- 17015180
- PMCID
- PMC2443724
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Language
- English
- Date published
- 10/15/2006
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984046826402771
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