Abstract
The heme based respiratory proteins myoglobin and hemoglobin can, under certain conditions, exhibit a peroxidase-like enzymic activity, in which a catalytic cycle, driven by peroxides, leads to oxidation of bio molecules. These heme proteins are implicated in what is termed "oxidative stress" as this catalytic cycle, when it occurs in vivo, generates cytotoxic product that are implicated in the pathology of a number of disease states. Here we review the evidence that such reactions occur in vivo, in particular in animal models and human patients and examine the underlying chemical mechanism. This mechanism involves the production of ferryl heme (FeIV=O2-) and it is this and associated radicals that initiate processes such as lipid peroxidation and the generation of bioactive molecules such as isoprostanes. The reactivity of the high oxidation state of the heme also allows us to identify unambiguous biomarkers for its presence in vivo in such conditions as rhabdomyolysis and brain hemorrhage. Ways to inhibit the peroxidatic cycle are discussed and the role of iron chelators such as desferrioxamine is discussed in terms of their often neglected properties as reducing agents. Suppression of the peroxidatic activity of hemoglobin is discussed in the context of the development of blood substitutes.
Keywords: myoglobin, hemoglobin, oxidative stress, lipid oxidation, heme to protein cross-linking, isoprostanes, heme oxygenase
Current Medicinal Chemistry
Title: Hemoglobin and Myoglobin Associated Oxidative Stress: from Molecular Mechanisms to Disease States
Volume: 12 Issue: 23
Author(s): Brandon J. Reeder and Michael T. Wilson
Affiliation:
Keywords: myoglobin, hemoglobin, oxidative stress, lipid oxidation, heme to protein cross-linking, isoprostanes, heme oxygenase
Abstract: The heme based respiratory proteins myoglobin and hemoglobin can, under certain conditions, exhibit a peroxidase-like enzymic activity, in which a catalytic cycle, driven by peroxides, leads to oxidation of bio molecules. These heme proteins are implicated in what is termed "oxidative stress" as this catalytic cycle, when it occurs in vivo, generates cytotoxic product that are implicated in the pathology of a number of disease states. Here we review the evidence that such reactions occur in vivo, in particular in animal models and human patients and examine the underlying chemical mechanism. This mechanism involves the production of ferryl heme (FeIV=O2-) and it is this and associated radicals that initiate processes such as lipid peroxidation and the generation of bioactive molecules such as isoprostanes. The reactivity of the high oxidation state of the heme also allows us to identify unambiguous biomarkers for its presence in vivo in such conditions as rhabdomyolysis and brain hemorrhage. Ways to inhibit the peroxidatic cycle are discussed and the role of iron chelators such as desferrioxamine is discussed in terms of their often neglected properties as reducing agents. Suppression of the peroxidatic activity of hemoglobin is discussed in the context of the development of blood substitutes.
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Cite this article as:
Reeder J. Brandon and Wilson T. Michael, Hemoglobin and Myoglobin Associated Oxidative Stress: from Molecular Mechanisms to Disease States, Current Medicinal Chemistry 2005; 12 (23) . https://dx.doi.org/10.2174/092986705774463021
DOI https://dx.doi.org/10.2174/092986705774463021 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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