Free radicals in iron-containing systems

doi:10.1016/0891-5849(87)90019-0

Free Radical Biology and Medicine

Volume 3, Issue 6, 1987, Pages 405-421

https://doi.org/10.1016/0891-5849(87)90019-0 Get rights and content

Abstract

All oxidative damage in biological systems arises ultimately from molecular oxygen. Molecular oxygen can scavenge carbon-centered free radicals to form organic peroxyl radicals and hence organic hydroperoxides. Molecular oxygen can also be reduced in two one-electron steps to hydrogen peroxide in which case superoxide anion is an intermediate; or it can be reduced enzymatically so that no superoxide is released. Organic hydroperoxides or hydrogen peroxide can diffuse through membranes whereas hydroxyl radicals or superoxide anion cannot. Chain reactions, initiated by chelated iron and peroxidase, can cause tremendous damage. Chain carriers are chelated ferrous ion; hydroxyl radical ·OH, or alkoxyl radical ·OR, and superoxide anion O₂^⪰ or organic peroxyl radical RO₂·. Of these free radicals ·OH and RO₂· appear to be most harmful. All of the biological molecules containing iron are potential donors of iron as a chain initiator and propagator. An attacking role for superoxide dismutase is proposed in the phagocytic process in which it may serve as an intermediate enzyme between NADPH oxidase and myeloperoxidase. The sequence of reactants is $O_{2} → O_{2}^{⪰} → H_{2} O_{2} → HOCI$ .

References (173)

C. Walling et al.
Kinetics of the decomposition of hydrogen peroxide catalyzed by the ferric-EDTA complex
M. Tien et al.
The multiple effects of ethylenediaminetetraacetate in several model lipid peroxidation systems
Arch. Biochem. Biophys.
(1982)
D.E. Feierman et al.
The effect of EDTA and iron on the oxidation of hydroxyl radical scavenging agents and ethanol by rat liver microsomes
Biochem. Biophys. Res. Commun.
(1983)
C.C. Winterbourn et al.
Iron and xanthine oxidase catalyze formation of an oxidant species distinguishable from hydroxyl radical: comparison with the Haber-Weiss reaction
Arch. Biochem. Biophys.
(1986)
H. Rosen et al.
Role of iron and EDTA in the bacterial activity of a superoxide anion-generating system
Arch. Biochem. Biophys.
(1981)
G.R. Buettner et al.
Kinetics of the reactions of superoxide radical with Fe(III) complexes of EDTA, DETAPAC and HEDTA
FEBS Lett.
(1983)
G. Cohen et al.
The Fenton reaction between ferrous diethylenetriaminepentaacetic acid and hydrogen peroxide
FEBS Lett.
(1982)
J.L. Zweier
Reduction of oxygen by iron-adriamycin
J. Biol. Chem.
(1984)
J.V. Bannister et al.
The production of hyroxyl radicals by adriamycin in red blood cells
FEBS Lett.v
(1983)
C.E. Myers et al.
Oxidative destruction of erythrocyte ghost membranes by the doxorubicin-iron complex
Biochemistry
(1982)

J.R. Kanofsky et al.

J. Biol. Chem.

(1986)

K. Hiraiwa et al.

Effect of bleomycin on lipid peroxides, glutathione peroxidase and collegenase in cultured lung fibroblasts

J. Biochem.

(1983)

R.A. Floyd et al.

Hydroxyl free radical formation from hydrogen peroxide by ferrous iron-nucleotide complexes

Biochemistry

(1983)

R.A. Floyd

DNA-ferrous iron catalyzed hydroxyl free radical formation from hydrogen peroxide

Biochem. Biophys. Res. Commun.

(1981)

A. Masini

The effect of ferric ion complex on isolated rat liver mitochondria. I. Respiratory and electrochemical responses

Biochim. Biophys. Acta

(1985)

B. Kalyanaraman et al.

A direct ESR and spin-trap investigation of peroxyl free radical formation by hematin/hydroperoxide systems

J. Biol. Chem.

(1983)

R.L. Aft et al.

Hemin-mediated oxidative degradation of proteins

J. Biol. Chem.

(1984)

R.A. Thaller et al.

Potential use of radiolabelled porphyrins for tumor scanning

Adv. Expt. Med. Biol.

(1983)

M. Noguchi et al.

A stoichiometric study of heme degradation catalyzed by the reconstructed heme oxygenase system with specific consideration of production of hydrogen peroxide during the reaction

J. Biochem.

(1983)

A.L. Balch et al.

Oxidation of red ferryl [(Fe^IVO)²⁺] porphyrin complexes to green ferryl [(Fe^IVO)²⁺] porphyrin radical complexes

J. Am. Chem. Soc.

(1985)

R.R. Crichton

Ferritin—the structure and function of an iron storage protein

M. O'Connell et al.

Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosident formation a biological protective mechanism?

Biochem. J.

(1986)

P. Biemond et al.

Superoxide-dependent and independent mechanisms of iron mobilization from ferritin by xanthine oxidase. Implications for oxygen-free-radical induced tissue destruction during ischaemia and inflammation

Biochem. J.

(1986)

H.B. Dunford

Kinetic and isotopic studies of acid-base catalysis in peroxidase reactions

J.M.C. Gutteridge

Iron promoters of the Fenton reaction and lipid peroxidation can be released from hemoglobin by peroxides

FEBS Lett.

(1986)

D. Ringe et al.

Reaction of myoglubin with phenylhydrazine: a molecular doorstop

Biochemistry

(1984)

J. Kanner et al.

Initiation of membranal lipid peroxidation by activated metmyoglobin and methemoglobin

Arch. Biochem. Biophys.

(1985)

D.A. Bates et al.

Reactions of adriamycin with hemoglobin. Superoxide dismutase indirectly inhibits reactions of the adriamycin semiquinone

Biochem. J.

(1982)

I. Moura et al.

Simple iron-sulfur proteins: methodology for establishing the type of center

H.B. Dunford

Peroxidases

Adv. Inorg. Biochem.

(1982)

M.A. Kashem et al.

Kinetics of the oxidation of reduced nicotinamide adenine dinucleotide by horseradish peroxidase compound I and II

Biochem. Cell Biol.

(1986)

R.F. Anderson

Energetics of the one-electron steps in the NAD⁺/NADH redox couple

Biochim. Biophys. Acta

(1980)

E.J.H. Bechara et al.

Peroxidase catalyzed generation of triplet acetone

Photochem. Photobiol.

(1979)

A. Boveris et al.

Organ chemiluminescence: non-invasive assay for oxidative free radical reactions

C.A. Coulson

Valence

H.B. Dunford

Elements of Diatomic Molecular Spectra

B.R. James

Interaction of dioxygen with metalloporphyrins

L.M. Dorfman et al.

Reactivity of the hydroxyl radical in aqueous solutions

National Standards Research Data System. National Bureau of Standards Bulletin No. 46

(1973)

B.H.J. Bielski et al.

Mechanism of disproportionation of superoxide radicals

J. Phys. Chem.

(1977)

B.H.J. Bielski

Reevaluation of the spectral and kinetic properties of HO₂ and O₂⁻ free radicals

Photochem. Photobiol.

(1978)

F. Haber et al.

Unpaarigkeit und radikalketten in reaktionsmechanismes organischer und enzymatischer vorgänge

Ber.

(1931)

F. Haber et al.

The catalytic decomposition of hydrogen peroxide by iron salts

W.G. Barb et al.

Reactions of ferrous and ferric ions with hydrogen peroxide. Part I. The ferrous ion reactions. Part II. The ferric ion reaction

Trans. Faraday Soc.

(1957)

W.G. Barb et al.

Reactions of ferrous and ferric ions with hydrogen peroxide. Part I. The ferrous ion reaction. Part II. The ferric ion reaction

Trans. Faraday Soc.

(1957)

Yu.N. Kozlov et al.

Initiation process in the system Fe³⁺ + H₂O₂

Int. J. Chem. Kinetics

(1974)

M.G. Evans et al.

The [Fe(OH)]⁺² and [Fe(O₂H]⁺² complexes

Trans. Faraday Soc.

(1949)

M.L. Kremer

Nature of intermediates in the catalytic decomposition of hydrogen peroxide by ferric ions

Trans. Faraday Soc.

(1962)

M.L. Kremer

Oxidation reduction step in catalytic decomposition of hydrogen peroxide by ferric ions

Trans. Faraday Soc.

(1963)

M.L. Kremer et al.

Kinetics of the Fe³⁺ ion-H₂O₂ reaction: steady-state and terminal-state analysis

Int. J. Chem. Kinetics

(1977)

C. Walling et al.

Oxygen evolution as a critical test of mechanism in the ferric-ion catalyzed decompostion of hydrogen peroxide

Int. J. Chem. Kinetics

(1977)

H.J.H. Fenton

Oxidation of tartaric acid in presence of iron

J. Chem. Soc.

(1894)

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^∗: H. Brian Dunford received his B.S. in Honors Chemistry and M.S. in Chemistry from the University of Alberta, and his Ph.D. in Chemistry from McGill University in Montreal. He has been with the Department of Chemistry of the University of Alberta in Canada since 1957, where he served as Chairman of the Physical-Theoretical Division from 1980 to 1984. He took sabbaticals with R.A. Alberty, University of Wisconsin, 1965–1966, and with R. J. P. Williams, Oxford University and B. G. Malmstrom and T. Vanngard, University of Gothenburg, Sweden 1972–1973. He won the Union Carbide Award for chemical education in 1980, and was made a fellow of the Chemical Institute of Canada in 1965. His research areas include kinetics and mechanisms of heme enzyme reactions; oxygen radical damage in biological systems; myeloperoxidase and the phagocytic process; inflammation, carcinogenesis and aging.

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Free radicals in iron-containing systems

Abstract

Arch. Biochem. Biophys.

Biochem. Biophys. Res. Commun.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

FEBS Lett.

FEBS Lett.

J. Biol. Chem.

FEBS Lett.v

Biochemistry

J. Biol. Chem.

J. Biochem.

Biochemistry

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

Adv. Expt. Med. Biol.

J. Biochem.

J. Am. Chem. Soc.

Biochem. J.

Biochem. J.

FEBS Lett.

Biochemistry

Arch. Biochem. Biophys.

Biochem. J.

Adv. Inorg. Biochem.

Biochem. Cell Biol.

Biochim. Biophys. Acta

Photochem. Photobiol.

Valence

Elements of Diatomic Molecular Spectra

Interaction of dioxygen with metalloporphyrins

Reactivity of the hydroxyl radical in aqueous solutions

National Standards Research Data System. National Bureau of Standards Bulletin No. 46

Mechanism of disproportionation of superoxide radicals

J. Phys. Chem.

Reevaluation of the spectral and kinetic properties of HO2 and O2− free radicals

Photochem. Photobiol.

Unpaarigkeit und radikalketten in reaktionsmechanismes organischer und enzymatischer vorgänge

Ber.

The catalytic decomposition of hydrogen peroxide by iron salts

Reactions of ferrous and ferric ions with hydrogen peroxide. Part I. The ferrous ion reactions. Part II. The ferric ion reaction

Trans. Faraday Soc.

Reactions of ferrous and ferric ions with hydrogen peroxide. Part I. The ferrous ion reaction. Part II. The ferric ion reaction

Trans. Faraday Soc.

Initiation process in the system Fe3+ + H2O2

Int. J. Chem. Kinetics

The [Fe(OH)]+2 and [Fe(O2H]+2 complexes

Trans. Faraday Soc.

Nature of intermediates in the catalytic decomposition of hydrogen peroxide by ferric ions

Trans. Faraday Soc.

Oxidation reduction step in catalytic decomposition of hydrogen peroxide by ferric ions

Trans. Faraday Soc.

Kinetics of the Fe3+ ion-H2O2 reaction: steady-state and terminal-state analysis

Int. J. Chem. Kinetics

Oxygen evolution as a critical test of mechanism in the ferric-ion catalyzed decompostion of hydrogen peroxide

Int. J. Chem. Kinetics

Oxidation of tartaric acid in presence of iron

J. Chem. Soc.

Reevaluation of the spectral and kinetic properties of HO₂ and O₂⁻ free radicals

Initiation process in the system Fe³⁺ + H₂O₂

The [Fe(OH)]⁺² and [Fe(O₂H]⁺² complexes

Kinetics of the Fe³⁺ ion-H₂O₂ reaction: steady-state and terminal-state analysis