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Journal ArticleDOI

Superoxide Radical and Superoxide Dismutases

Irwin Fridovich1
01 Jan 1995-Annual Review of Biochemistry (Annual Reviews 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139, USA)-Vol. 64, Iss: 1, pp 97-112
TL;DR: O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH..
Abstract: O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH. production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O2-. Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.
Citations
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Journal ArticleDOI
TL;DR: This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments and discusses various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.
Abstract: The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2−•). Even though O2−• is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.

4,282 citations


Cites background or methods from "Superoxide Radical and Superoxide D..."

  • ...Similarly, luminol and lucigenin may also produce O2 _• during their oxidation, leading to the false conclusion that O2 _• was actually formed in the process (Liochev & Fridovich, 1998)....

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  • ...Superoxide is enzymatically converted to H2O2 by a family of metalloenzymes called superoxide dismutases (SOD; Fridovich, 1995)....

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  • ...Many of these methods rely on the redox properties of specific ROS or RNS, and therefore are prone to artifacts caused by species of similar reactivity or by reactive intermediates produced by the probe itself (Picker & Fridovich, 1984; Faulkner & Fridovich, 1993; Liochev & Fridovich, 1995, 1998)....

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  • ...For example, a research group concluded that O2 _• was produced by the enzyme glucose oxidase because superoxide dismutase inhibited the reduction of nitroblue tetrazolium in the presence of glucose, when in reality the probe was reacting with the enzyme’s prosthetic group and O2 _• was formed after this reaction (Al-Bekairi et al. 1994; Liochev & Fridovich, 1995)....

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  • ...…enzyme glucose oxidase because superoxide dismutase inhibited the reduction of nitroblue tetrazolium in the presence of glucose, when in reality the probe was reacting with the enzyme’s prosthetic group and O2 _• was formed after this reaction (Al-Bekairi et al. 1994; Liochev & Fridovich, 1995)....

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Book
01 Jan 1982
TL;DR: In this article, the Soil as a Plant Nutrient Medium is discussed and the importance of water relations in plant growth and crop production, and the role of water as a plant nutrient medium.
Abstract: 1. Plant Nutrients. 2. The Soil as a Plant Nutrient Medium. 3. Nutrient Uptake and Assimilation. 4. Plant Water Relationships. 5. Plant Growth and Crop Production. 6. Fertilizer Application. 7. Nitrogen. 8. Sulphur. 9. Phosphorus. 10. Potassium. 11. Calcium. 12. Magnesium. 13. Iron. 14. Manganese. 15. Zinc. 16. Copper. 17. Molybdenum. 18. Boron. 19. Further Elements of Importance. 20. Elements with More Toxic Effects. General Readings. References. Index.

4,130 citations

Journal ArticleDOI
TL;DR: The status of the free radical theory of aging is reviewed, by categorizing the literature in terms of the various types of experiments that have been performed, which include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, and the ongoing elucidation of the role of active oxygen in biology.
Abstract: Beckman, Kenneth B., and Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547–581, 1998. — The free radical theory of aging, conceived in 1956, has turned 40 and is rapidl...

3,812 citations

Journal ArticleDOI
TL;DR: The evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated is examined.
Abstract: Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When cellular production of ROS overwhelms its antioxidant capacity, damage to cellular macromolecules such as lipids, protein, and DNA may ensue. Such a state of “oxidative stress” is thought to contribute to the pathogenesis of a number of human diseases including those of the lung. Recent studies have also implicated ROS that are generated by specialized plasma membrane oxidases in normal physiological signaling by growth factors and cytokines. In this review, we examine the evidence for ligand-induced generation of ROS, its cellular sources, and the signaling pathways that are activated. Emerging concepts on the mechanisms of signal transduction by ROS that involve alterations in cellular redox state and oxidative modifications of proteins are also discussed.

2,757 citations

Journal ArticleDOI
TL;DR: After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases.
Abstract: The brain and nervous system are prone to oxidative stress, and are inadequately equipped with antioxidant defense systems to prevent 'ongoing' oxidative damage, let alone the extra oxidative damage imposed by the neurodegenerative diseases. Indeed, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in protein clearance constitute complex intertwined pathologies that conspire to kill neurons. After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases.

2,430 citations


Cites background from "Superoxide Radical and Superoxide D..."

  • ...Hence, the toxicity of excess O2 is thought to be due (Fridovich 1995) to increased formation of O 2 –....

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  • ...Hence, the toxicity of excess O2 is thought to be due (Fridovich 1995) to increased formation of O 2 ....

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  • ...All parts of the nervous system contain SODs, enzymes that remove O 2 by catalyzing its dismutation, one O 2 being reduced to H2O2 and another oxidized to O2 (Fridovich 1989, 1995; Halliwell 2001; Liochev and Fridovich 2005) 2O 2 þ 2Hþ !...

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References
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Journal ArticleDOI
TL;DR: The demonstration that O2·- can reduce ferricytochrome c and tetranitromethane, and that superoxide dismutase, by competing for the superoxide radicals, can markedly inhibit these reactions, is demonstrated.

12,468 citations

Journal ArticleDOI
TL;DR: The staining procedure for localizing superoxide dismutase on polyacrylamide electrophoretograms has been applied to extracts obtained from a variety of sources and could thus be assayed either in crude extracts or in purified protein fractions.

10,933 citations

Journal ArticleDOI
TL;DR: The autoxidation of pyrogallol was investigated in the presence of EDTA in the pH range 7.9–10.6, indicating an almost total dependence on the participation of the superoxide anion radical, O2·−, in the reaction.
Abstract: The autoxidation of pyrogallol was investigated in the presence of EDTA in the pH range 7.9–10.6. The rate of autoxidation increases with increasing pH. At pH 7.9 the reaction is inhibited to 99% by superoxide dismutase, indicating an almost total dependence on the participation of the superoxide anion radical, O2·−, in the reaction. Up to pH 9.1 the reaction is still inhibited to over 90% by superoxide dismutase, but at higher alkalinity, O2·− -independent mechanisms rapidly become dominant. Catalase has no effect on the autoxidation but decreases the oxygen consumption by half, showing that H2O2 is the stable product of oxygen and that H2O2 is not involved in the autoxidation mechanism. A simple and rapid method for the assay of superoxide dismutase is described, based on the ability of the enzyme to inhibit the autoxidation of pyrogallol. A plausible explanation is given for the non-competitive part of the inhibition of catechol O-methyltransferase brought about by pyrogallol.

9,030 citations

Journal ArticleDOI
TL;DR: It is proposed that the autoxidation of epinephrine proceeds by at least two distinct pathways, only one of which is a free radical chain reaction involving O2- and hence inhibitable by superoxide dismutase.

7,872 citations

Journal ArticleDOI
TL;DR: The reduction of nitro blue tetrazolium (NitroBT) with NADH mediated by phenazine methosulfate (PMS) under aerobic conditions was inhibited upon addition ofsuperoxide dismutase, indicating the involvement of superoxide aninon radical in the reduction of NitroBT.

3,331 citations