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Updated: May 9, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
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Published on: February 24, 2018

Cytochrome c and superoxide.

Willem H Koppenol1

  • 1Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093, Zürich, Switzerland, koppenol@inorg.chem.ethz.ch.

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
|July 19, 2013
PubMed
Summary
This summary is machine-generated.

The reduction of iron(III) cytochrome c by superoxide follows a solvent-accessible heme edge electron transfer mechanism. Previous claims of a new mechanism are refuted due to methodological deficiencies.

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Area of Science:

  • Biochemistry
  • Bioinorganic Chemistry
  • Electron Transfer Mechanisms

Background:

  • Human cytochrome c is a crucial protein in cellular respiration.
  • Superoxide is a reactive oxygen species involved in various biological processes.
  • Previous studies proposed novel mechanisms for the reduction of iron(III) cytochrome c by superoxide.

Purpose of the Study:

  • To re-evaluate the proposed mechanism for the reduction of iron(III) cytochrome c by superoxide.
  • To demonstrate the continued validity of the solvent-accessible heme edge electron transfer mechanism.
  • To identify and address deficiencies in the work by Wegerich et al.

Main Methods:

  • Analysis of electron transfer pathways in singly modified human cytochromes c.
  • Critique of experimental methodologies and data interpretation in Wegerich et al.
  • Comparison of proposed mechanisms with established biochemical principles.

Main Results:

  • Electron transfer via the solvent-accessible heme edge remains the predominant mechanism.
  • The mechanism proposed by Wegerich et al. is not supported by the evidence.
  • Significant methodological flaws in Wegerich et al. prevent valid comparisons.

Conclusions:

  • The solvent-accessible heme edge mechanism is the correct pathway for iron(III) cytochrome c reduction by superoxide.
  • The findings of Wegerich et al. are invalidated by critical deficiencies.
  • Further research must address these methodological issues for accurate comparisons in bioinorganic chemistry.