Chemical, Biological and Medical Controversies Surrounding the Fenton Reaction

Abstract

A critical evaluation is made of the role of the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH-) in the promotion of oxidative damage in mammalian systems. Following a brief, historical overview of the Fenton reaction, including the formulation of the Haber–Weiss cycle as a mechanism for the catalysis of hydroxyl radical production, an appraisal is made of the biological relevance of the reaction today, following recognition of the important role played by nitric oxide and its congers in the promotion of biomolecular damage. In depth coverage is then given of the evidence (largely from EPR studies) for and against the hydroxyl radical as the active oxidant produced in the Fenton reaction and the role of metal chelating agents (including those of biological importance) and ascorbic acid in the modulation of its generation. This is followed by a description of the important developments that have occurred recently in the molecular and cellular biology of iron, including evidence for the presence of ‘free’ iron that is available in vivo for the Fenton reaction. Particular attention here is given to the role of the iron-regulatory proteins in the modulation of cellular iron status and how their functioning may become dysregulated during oxidative and nitrosative stress, as well as in hereditary haemochromatosis, a common disorder of iron metabolism. Finally, an assessment is made of the biological relevance of ascorbic acid in the promotion of hydroxyl radical generation by the Fenton reaction in health and disease.

A Single-Electron Reducing Quinone Oxidoreductase Is Necessary to Induce Haustorium Development in the Root Parasitic Plant Triphysaria

“…These reactions generate highly reactive free radical semiquinones that in the presence of oxygen are rapidly oxidized to the quinone, with the concomitant formation of the superoxide anion radical O 2 d 2 (Figure 9). Semiquinones and superoxide radicals are cytotoxic, as are the hydroxyl radicals formed subsequently by the Fenton reaction (Burkitt, 2003). By contrast, two electron quinone reductions catalyzed by enzymes like DT-diaphorase do not generate (D) Reduction of cytochrome c by QR1.…”

Reactive oxygen species responsible for beta-glucan degradation

“…Å OH are known to be generated via the iron catalysed Haber-Weiss cycle and the ascorbatedriven Fenton reaction (Burkitt & Gilbert, 1990;Haber & Weiss, 1932). However, the reaction pathways that lead to the formation of Å OH are still controversial (Burkitt, 2003;Koppenol, 2001). Moreover, previous studies dealing with Å OH-induced beta-glucan degradation have not focused on studying the mechanism involved in the formation of Å OH.…”

“…(2) and (3), thus supplying the substrates necessary to produce Å OH (Buettner & Jurkiewicz, 1996;Fry, 1998): This process, in which ascorbate recycles iron(III) to iron(II) and maintains the Fenton reaction, is called ascorbate-driven Fenton reaction (Burkitt, 2003). Similar to xyloglucan, beta-glucan may suffer from Å OH-induced oxidative cleavage in an AH 2 /iron(II) system.…”

The effect of metal chelators on the production of hydroxyl radicals in thylakoids

“…Anyway, this was not confirmed by other authors (Buettner et al 1983;Engelmann et al 2003). The free coordination site is probably more crucial for the reduction of Fe 3+ -chelator complex than for the Fenton reaction itself (Burkitt 2003), however, the situation remains puzzling up today.…”