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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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Devi, S., Kumar, V., Singh, S. K., Dubey, A. K., & Kim, J.-J. (2021) · Biomedicines · doi:10.3390/biomedicines9020099 · Cited by 124
“These free radicals react with hydrogen peroxide (H2O2) via the iron-catalyzed Haber–Weiss reaction that generates the hydroxyl radical (•OH) [31,32].”
BackgroundČapek, J., & Roušar, T. (2021) · Molecules · doi:10.3390/molecules26164710 · Cited by 128
Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments
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“Intracellular iron that is not bound to proteins or chelated can act as a catalyst for the Haber-Weiss reaction and participate in Fenton reactions, leading to the generation of toxic hydroxyl radicals (199, 200).”
BackgroundUnequivocal Role of Pyrazine Ring in Medicinally Important Compounds: A Review
Miniyar, P. B., Murumkar, P. R., Patil, P., Barmade, M. A., & Bothara, K. G. (2013) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557511313110007 · Cited by 122
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Iron Homeostasis in Healthy Kidney and its Role in Acute Kidney Injury
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Total antioxidant capacity—Relevance, methods and clinical implications
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“CAT and GPx, in turn, convert O − 2 into molecular oxygen or alcohols, respectively, contributing to the removal of oxidants (Kehrer, 2000; Valko, Izakovic, Mazur, Rhodes, & Telser, 2004).”
BackgroundNanozymes towards Personalized Diagnostics: A Recent Progress in Biosensing
Kurup, C. P., & Ahmed, M. U. (2023) · Biosensors · doi:10.3390/bios13040461 · Cited by 122
“tions” in the presence of strong catalytic metal ions (often iron ions) [45].”
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Nitric Oxide and Superoxide, a Deadly Cocktail
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Role of iron in neurodegenerative diseases
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“Through Fenton and Haber–Weiss reactions, the most reactive oxygen species (ROS) hydroxyl radicals are produced (Wardman and Candeias 1996; Kehrer 2000).”
Free Radicals and Reactive Oxygen Species
Kehrer, J. P., Robertson, J. D., & Smith, C. V. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-046884-6.00114-7 · Cited by 132
Self-citationMetal/Metal Oxide Nanoparticles: Toxicity, Applications, and Future Prospects
Chaudhary, R. G., Bhusari, G. S., Tiple, A. D., Rai, A. R., SOMKUWAR, S. R., Potbhare, A. K., Lambat, T. L., Ingale, P. P., & Abdala, A. A. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191111091326 · Cited by 117
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“The antioxidant potential of this extract was assessed using a number of assays: the DPPH assay was used to measure the free radical scavenging ability [38]; the FRAP assay was used to measure the reducing power (Fe3+ to Fe2+); and, the iron-binding assay was used to measure the ability to chelate transition metal iro…”
MethodInsights into Diabetic Kidney Disease Using Urinary Proteomics and Bioinformatics
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The mechanisms of ferroptosis and its role in alzheimer’s disease
Ma, H., Dong, Y., Chu, Y., Guo, Y., & Li, L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.965064 · Cited by 115
“Specifically, the ROS H2O2 oxidizes Fe 2+ to Fe3+ via the Fenton reaction, forming the highly active hydroxyl radical (·OH), inducing oxidative stress and leading to ferroptosis, the accumulation of lipoid-OOH, and the oxidation of polyunsaturated fatty acids (PUFAs) (Kehrer, 2000; Qi et al., 2020).”
BackgroundYang, X., Kawasaki, N. K., Min, J., Matsui, T., & Wang, F. (2022) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2022.10.004 · Cited by 117
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“oxide H2O2 was proposed by Joseph Weiss [13].”
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“As expected, we discovered previously known mechanisms including efflux of metal ions by P1 ATPases, downregulation of Mn(II) uptake, ion scavenging, increased protein turnover, and minimizing ROS production; however, it is noteworthy to mention that these are all new insights for archaea.”
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“Fe (II) + H2O2 → Fe (III) + OH− + OH• (1) The ferric iron can then react with superoxide in the Haber–Weiss reaction (Kehrer, 2000) generating Fe(II) again, thereby effecting redox cycling: O•−2 + Fe (III) → O2 + Fe (II) (2) In other words, catalytic quantities of unliganded or poorly liganded iron…”
BackgroundGp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH
Deng, S., Kruger, A., Kleschyov, A. L., Kalinowski, L., Daiber, A., & Wojnowski, L. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.013 · Cited by 109
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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