Metal Ions in Biological Systems

Volume 36: Interrelations Between Free Radicals and Metal Ions in Life Processes

Astrid Sigel, Helmut Sigel

• Publisher: CRC Press
• Year: 2018
• ISBN:
  9781351432139
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Chemistry
• Index: Chemistry

Continues the tradition of excellence established in previous volumes in this acclaimed series. Volume 36 focuses on the vibrant research area concerning the interrelation between free radicals and metal ions and their resulting effects on life processes; it offers an authoritative and timely account of this fascinating area of research in 21 chapters.

Chapter 1

The Mechanism of “Fenton-Like” Reactions and Their Importance for Biological Systems. A Biologist’s View

Stefan I. Liochev

Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA

1. INTRODUCTION

2. THE FENTON REACTION AND FENTON-LIKE REACTIONS

2.1. The Classical Fenton Reaction

2.2. Other Metal Complexes Replacing Fe(II)

2.3. Other Peroxides Replacing Hydrogen Peroxide

2.4. Is HO^∙ the (Only) Reactive Species Generated?

2.5. The Haber-Weiss Reaction: Superoxide Radical Acting as Reductant for Fe(III)

2.6. Other Reductants Replacing Superoxide Radical

2.7. In Vitro Damage Caused by Fenton-like Reactions

2.8. Site-Specific Fenton-like Reactions and Caged HO^∙

2.9. The Ability of Metal-Containing Proteins to Catalyze Fenton-like Reactions

2.9.1. Iron-Sulfur Cluster-Containing Proteins

2.9.2. Cu,Zn Superoxide Dismutase

2.9.3. Others

2.10. Additional Aspects in Vitro

3. SIGNIFICANCE OF THE FENTON-LIKE REACTIONS IN VIVO

3.1. Existence and Nature of the Cellular “Free” Iron Pools

3.2. Intra- and Extracellular Sources of Free Iron, Hydrogen Peroxide, and Superoxide

3.2.1. Hydrogen Peroxide and Superoxide

3.2.2. Sources of Iron

3.3. Evidence of Damage to DNA and Other Biomolecules: Some Questions

3.4. Superoxide Radical: Reductant or Oxidant?

3.5. The Role of Iron-Sulfur Clusters

3.6. The Central Role of the Fenton-like Reactions in Oxidative Stress

3.7. Selected Examples of Possible Involvement of Fenton-like Reactions in Vivo

3.7.1. MnSOD-Deficient Mice

3.7.2. Aging

3.7.3. Friedreich’s Ataxia

3.7.4. Cancer and Tumor Necrosis Factor Cytotoxicity

3.7.5. Amyotrophic Lateral Sclerosis

3.7.6. Others

3.8. Adaptations to Oxidative Stress and Iron Toxicity

4. CONCLUSIONS

ACKNOWLEDGMENTS

ABBREVIATIONS

REFERENCES

1. INTRODUCTION

It seems appropriate to begin this chapter by defining terms. Reaction (1) is the Fenton reaction.

$\text{Fe(II)}\text{+}{\text{H}}_2{\text{O}}_2\to \text{Fe(III)}\text{+}{\text{HO}}^{•}+{\text{HO}}^{-}$

(1)

The term “Fenton-like reactions” is often used when transition metal complexes replace Fe(II). Here I would like to give a more expanded definition of this term, i.e., all reactions describing the reduction of peroxides of any kind by transition metal complexes.

These reactions play a central role in oxidative stress and in the overlapping phenomenon of toxicity caused by transition metal ions (complexes). The chemistry of the Fenton-like reactions (FLRs) is described in Sect. 2 of this chapter and the role of FLRs in causing oxidative stress in vivo is discussed in Sect. 3. In both cases, more attention is paid to the processes that precede FLRs and allow them to occur than to the damage caused by the hydroxyl radical (HO^•) and by other products of FLRs. In Sect. 3 the processes of adaptation of the cells to oxidative stress are also discussed, with emphasis on the fact that to a significant extent the biological significance of these adaptations is to prevent FLRs from occurring and to repair the damage when they do occur.

It should be stated that this field has grown so vast that discussing, or even citing, most of the important contributions is virtually impossible; therefore, the reader is often referred to reviews. Even so, important aspects might, and will, remain uncovered, whereas problems of special interest to this author will be discussed in more detail. It is hoped that such problems might also be of interest to the reader.

2. THE FENTON REACTION AND FENTON-LIKE REACTIONS

2.1. The Classical Fenton Reaction

Although Fenton [1] was the first to describe a reaction dependent on both Fe(II) and H₂O₂, the mechanism of the Fenton reaction was initially studied and essentially discovered by Willstätter, Haber, and Weiss [2,3] and subsequently by Barb et al. [4]. Because this chemistry is so important for understanding the nature of oxidative stress, it deserves detailed exposition.

When H₂O₂ and Fe(II) are the only reactants, reaction (1) is just the first reaction of a complex process. In reaction (2) superoxide radical (${\text{O}}_2^{-}$) is generated through the oxidation of H₂O₂ by HO^•.

${\text{HO}}^{•}\text{+}{\text{H}}_2{\text{O}}_2\to {\text{O}}_2^{-}+{\text{H}}^{+}+{\text{H}}_2\text{O}$

(2)

The finding [2,3] that led to the proposal of the second most famous reaction in the free radical field was that at high H₂O₂/Fe(II) ratio more H₂O₂ was decomposed than Fe(III) formed, indicating a chain mechanism.

Reaction (3), which is now called the Haber-Weiss reaction, causes iron-independent decomposition of H₂O₂ and moreover regenerates HO^•. Thus the chain process consists of reactions (2) and (3) [2,3].

${\text{O}}_2^{-}+{\text{H}}_2{\text{O}}_2\to {\text{O}}_2+{\text{HO}}^{•}+{\text{HO}}^{-}$

(3)

It should be noted that HO₂^• and not ${\text{O}}_2^{-}$ is the reactant in the original papers. However, since at neutral pH ${\text{O}}_2^{-}$ predominate...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• PREFACE TO THE SERIES
• PREFACE TO VOLUME 36
• CONTRIBUTORS
• CONTENTS OF PREVIOUS VOLUMES
• Chapter 1 THE MECHANISM OF “FENTON-LIKE” REACTIONS AND THEIR IMPORTANCE FOR BIOLOGICAL SYSTEMS. A BIOLOGIST’S VIEW
• Chapter 2 REACTIONS OF ALIPHATIC CARBON-CENTERED AND ALIPHATIC-PEROXYL RADICALS WITH TRANSITION-METAL COMPLEXES AS A PLAUSIBLE SOURCE FOR BIOLOGICAL DAMAGE INDUCED BY RADICAL PROCESSES
• Chapter 3 FREE RADICALS AS A RESULT OF DIOXYGEN METABOLISM
• Chapter 4 FREE RADICALS AS A SOURCE OF UNCOMMON OXIDATION STATES OF TRANSITION METALS
• Chapter 5 BIOLOGICAL CHEMISTRY OF COPPER-ZINC SUPEROXIDE DISMUTASE AND ITS LINK TO AMYOTROPHIC LATERAL SCLEROSIS
• Chapter 6 DNA DAMAGE MEDIATED BY METAL IONS WITH SPECIAL REFERENCE TO COPPER AND IRON
• Chapter 7 RADICAL MIGRATION THROUGH THE DNA HELIX: CHEMISTRY AT A DISTANCE
• Chapter 8 INVOLVEMENT OF METAL IONS IN LIPID PEROXIDATION:BIOLOGICAL IMPLICATIONS
• Chapter 9 FORMATION OF METHEMOGLOBIN AND FREE RADICALS IN ERYTHROCYTES
• Chapter 10 ROLE OF FREE RADICALS AND METAL IONS IN THE PATHOGENESIS OF ALZHEIMER’S DISEASE
• Chapter 11 METAL BINDING AND RADICAL GENERATION OF PROTEINS IN HUMAN NEUROLOGICAL DISEASES AND AGING
• Chapter 12 THIYL RADICALS IN BIOCHEMICALLY IMPORTANT THIOLS IN THE PRESENCE OF METAL IONS
• Chapter 13 METHYLMERCURY-INDUCED GENERATION OF FREE RADICALS: BIOLOGICAL IMPLICATIONS
• Chapter 14 ROLE OF FREE RADICALS IN METAL-INDUCED CARCINOGENESIS
• Chapter 15 pH-DEPENDENT ORGANOCOBALT SOURCES FOR ACTIVE RADICAL SPECIES: A NEW TYPE OF ANTICANCER AGENTS
• Chapter 16 DETECTION OF CHROMATIN-ASSOCIATED HYDROXYL RADICALS GENERATED BY DNA-BOUND METAL COMPOUNDS AND ANTITUMOR ANTIBIOTICS
• Chapter 17 NITRIC OXIDE (NO): FORMATION AND BIOLOGICAL ROLES IN MAMMALIAN SYSTEMS
• Chapter 18 CHEMISTRY OF PEROXYNITRITE AND ITS RELEVANCE TO BIOLOGICAL SYSTEMS
• Chapter 19 NOVEL NITRIC OXIDE-LIBERATING HEME PROTEINS FROM THE SALIVA OF BLOODSUCKING INSECTS
• Chapter 20 NITROGEN MONOXIDE-RELATED DISEASE AND NITROGEN MONOXIDE SCAVENGERS AS POTENTIAL DRUGS
• Chapter 21 THERAPEUTICS OF NITRIC OXIDE MODULATION
• SUBJECT INDEX