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The Haber–Weiss reaction and mechanisms of toxicity
Abstract
The concept that the highly reactive hydroxyl radical (HO) could be generated from an interaction between superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) was proposed (with Joseph Weiss) in Professor Haber's final paper published in 1934. Until it was recognized that free radicals are produced in biological systems, this finding seemed to have no relevance to biology. However, following the discovery that O(2)(-) was a normal cellular metabolite, it was quickly recognized that the Haber-Weiss reaction (O(2)(-)+H(2)O(2) -->HO+O(2)+HO(-)) might provide a means to generate more toxic radicals. Although the basic reaction has a second order rate constant of zero in aqueous solution and thus cannot occur in biological systems, the ability of iron salts to serve as catalysts was discussed by these authors. Because transition metal ions, particularly iron, are present at low levels in biological systems, this pathway (commonly referred to as the iron-catalyzed Haber-Weiss reaction) has been widely postulated to account for the in vivo generation of the highly reactive HO. Recent data documenting the importance of redox regulation of various cellular signaling pathways makes it clear that free radicals are essential for normal cellular function. However, this also makes it obvious that disruptions of free radical production or defenses at many different levels can lead to adverse effects on cells. While the generation of HO, which is by far the most reactive oxygen species, is generally indicative of an overtly toxic event, it is through studies at this level that we have reached a better understanding of free radicals as both signaling molecules and toxic species.
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“Superoxide can also react with ferric iron in the Haber-Weiss reaction [67] to produce Fe(II) again, thereby effecting redox cycling:”
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“Superoxide (also produced by mitochondria) can react with ferric iron in the Haber-Weiss reaction (Kehrer 2000) to produce Fe(II) again, thereby effecting redox cycling of the iron (Fig. 1):2”
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“reactivity, H2O2 causes cellular damage after conversion to more reactive species such as ·OH, which has a single unpaired electron (Haber and Weiss, 1934; Kehrer, 2000).”
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“Furthermore, by combining a Fenton reaction with the reduction of +3 Fe by superoxide (Fe(III) + O2 Fe(II) + O2), the net reaction is known as the Haber-Weiss reaction (O2 + H2O2 O2 + OH + OH ), which results in the formation of the damaging hydroxyl radical from the interaction between superoxide radical and hydrogen…”
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“Iron also plays a role in other redox reactions within cells [4] and can participate in the Haber-Weiss reaction that leads to the generation of reactive oxygen species (ROS) [5].”
Background
Metadata
- Authors
- Kehrer, J. P.
- Affiliations
- The University of Texas at Austin (US)
- Corresponding author
- Kehrer, James P
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 149
- Issue
- 1
- Pages
- 43-50
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W2126473492
- Cited by
- 1,418
- References
- 39
- Citations by year
- 2026: 46 · 2025: 71 · 2024: 90 · 2023: 91 · 2022: 101 · 2021: 101 · 2020: 91 · 2019: 65 · 2018: 76 · 2017: 72 · 2016: 71 · 2015: 62 · 2014: 48 · 2013: 65 · 2012: 59
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01es009791-04, 5r01hl051005-05, 5r01hl048035-07)
- National Heart, Lung, and Blood Institute (HL 48035, HL 51005)
- National Institute of Environmental Health Sciences (ES09791)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Keywords
- Haber-Weiss reaction, hydroxyl radicals, superoxide, hydrogen peroxide, free radicals, reactive oxygen species, oxidative stress, redox signaling, toxicity mechanisms, transition metal catalysis
- MeSH terms
- Animals, Humans, Hydrogen Peroxide, Superoxides, Hydroxyl Radical, Oxidative Stress
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