Generation of superoxide radicals during the autoxidation of mammalian oxyhemoglobin

Wever, Ron; Oudega, Bauke; Gelder, B.F. Van

doi:10.1016/0005-2744(73)90180-0

Cited by 172 publications

(66 citation statements)

References 14 publications

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“…there is no lag in the formation of hemichrome), while step c is, under these conditions, very slow. At pH 6 the process was altogether very much slower, (1) 4 Precipitate. spectra were recorded every 5 min but still there was no evidence for precipitation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Firstly, the isolated chains autoxidize much faster than the natural tetramer, and thus 0; production might be revealed by the same experimental approach used previously [3,4]. Secondly, production of 0; by isolated chains may be involved in pathological phe- nomena observed in red blood cell diseases where excess of either a or p chains is produced because of inherited defects of synthesis.…”

mentioning

confidence: 90%

“…The possibility that this process could lead to the production of superoxide radical (02-) has been forecast because the structure of oxyhemoglobin has been postulated to be a superoxo-ferriheme complex (Fe3 during autoxidation has been obtained by using hemoglobin from shark [ 3 ] , which autoxidizes more rapidly than the mammalian proteins, or by testing mammalian oxyhemoglobin at high salt concentration and low pH [4]. The purpose of the work reported here is to look at 0; production during autoxidation of the isolated a and fi chains of human hemoglobin.…”

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confidence: 99%

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Formation of Superoxide in the Autoxidation of the Isolated alpha and beta Chains of Human Hemoglobin and Its Involvement in Hemichrome Precipitation

et al. 1975

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The purpose of the work reported here is to look at 0; production during autoxidation df the isolated a and fi chains of human hemoglobin. The formation of superoxide by isolated chains, in fact, may be involved in pathological phenomena observed in red blood cell diseases where excess of either a or fi chains is produced because of inherited defects of synthesis (thalassemus).The autoxidation of the oxygenated chains of human hemoglobin is followed by the transformation of the oxidized molecule (high-spin Fe3+) into a species absorbing as a low-spin Fe3+ compound, that is a hemichrome, which tends to precipitate. The overall process may be described by the following reactions :Oxychains -% Ferric chains % Hemichrome % Precipitate.Depending on conditions the different steps proceed with different relative rates and therefore may overlap to a greater or lesser extent.The results obtained indicate that superoxide is produced during autoxidation of the isolated a and B chains of human hemoglobin. This conclusion has been reached on the basis of an experimental approach based on cooxidation of epinephrine to adrenochrome during 0; production and inhibition of this effects by superoxide dismutase. In addition the rate of precipitation is, in all cases, very much reduced upon addition of either superoxide dismutase or catalase. These facts seem to imply very strongly that oxygen radicals are involved also in the precipitation following oxidation and hemichrome formation in the chains. In particular the effect of superoxide dismutase implies the involvement of 0,. Thus production of 0; ,could well be one of the important events leading to alteration of the red cell membrane and consequently to reduced life span of thalassemic erythrocytes.

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Section: Resultsmentioning

confidence: 99%

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confidence: 90%

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confidence: 99%

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Formation of Superoxide in the Autoxidation of the Isolated alpha and beta Chains of Human Hemoglobin and Its Involvement in Hemichrome Precipitation

et al. 1975

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“…Shikama (66) describes inner sphere and outer sphere electron transfer mechanisms of Mb autooxidation. Early work describes the iron atom in oxyhemoglobin to be ferric, which may suggest that the O 2 bound exists as the superoxide anion radical (80). Formation of met(III)Mb from …”

Section: Autooxidation Of Mbmentioning

confidence: 99%

Redox Reactions of Myoglobin

Richards

2013

Antioxidants & Redox Signaling

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Significance: Failure to maintain myoglobin (Mb) in the reduced state causes the formation of metMb, ferryl Mb species, and cross-linked Mb. Dissociation of ferriprotoporphyrin IX from the globin and release of iron atoms can also occur as oxidized Mb accumulates. These modifications may contribute to various oxidative pathologies in muscle and muscle foods. Recent Advances: The mechanism of ferryl Mb-mediated oxidative damage to nearby structures has been partially elucidated. Dissociation of ferriprotoporphyrin IX from metMb occurs more readily at acidic pH values. The dissociated ferriprotoporphyrin IX (also called hemin) readily decomposes preformed lipid hydroperoxides to reactive oxygen species. Heme oxygenase as well as lipophilic free radicals can degrade the protoporphyrin IX moiety, which results in the formation of free iron. Critical Issues: The multiple pathways by which Mb can incur toxicity create difficulties in determining the major cause of oxidative damage in a particular system. Peroxides and low pH activate each of the oxidative Mb forms, ferriprotoporphyrin IX, and released iron. Determining the relative concentration of these species is technically difficult, but essential to a complete understanding of oxidative pathology in muscle tissue. Future Directions: Improved methods to assess the different pathways of Mb toxicity are needed. Although significant advances have been made in the understanding of Mb interactions with other biomolecules, further investigation is needed to understand the physical and chemical nature of these interactions.

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“…Although predicted by Weiss (11), it was first shown by Wever et al (12) and Misra and Fridovich (13) without changing the overall stoichiometry. The rate of autoxidation increases as the pH is lowered, and also as P02 decreases, reaching a maximum at approx.…”

Section: Hemoglobin Autoxidatiormentioning

confidence: 96%

Free-radical production and oxidative reactions of hemoglobin.

Winterbourn¹

1985

Environ Health Perspect

153

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Mechanisms of autoxidation of hemoglobin, and its reactions with H2O2, O2-, and oxidizing or reducing xenobiotics are discussed. Reactive intermediates of such reactions can include drug free radicals, H2O2, and O2-, as well as peroxidatively active ferrylhemoglobin and methemoglobin-H2O2. The contributions of these species to hemoglobin denaturation and drug-induced hemolysis, and the actions of various protective agents, are considered.

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Generation of superoxide radicals during the autoxidation of mammalian oxyhemoglobin

Cited by 172 publications

References 14 publications

Formation of Superoxide in the Autoxidation of the Isolated alpha and beta Chains of Human Hemoglobin and Its Involvement in Hemichrome Precipitation

Formation of Superoxide in the Autoxidation of the Isolated alpha and beta Chains of Human Hemoglobin and Its Involvement in Hemichrome Precipitation

Redox Reactions of Myoglobin

Free-radical production and oxidative reactions of hemoglobin.

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