The radical and redox chemistry of myoglobin and hemoglobin: from in vitro studies to human pathology.
Recent research has shown that myoglobin and hemoglobin play important roles in the pathology of certain disease states, such as renal dysfunction following rhabdomyolysis and vasospasm following subarachnoid hemorrhages. These pathologies are linked to the interaction of peroxides with heme proteins to initiate oxidative reactions, including generation of powerful vasoactive molecules (the isoprostanes) from free and membrane- bound lipids. This review focuses on the peroxide-induced formation of radicals, their assignment to specific protein residues, and the pseudoperoxidase and prooxidant activities of the heme proteins. The discovery of heme to protein cross-linked forms of myoglobin and hemoglobin in vivo, definitive markers of the participation of these heme proteins in oxidative reactions, and the recent results from heme oxygenase knockout/knockin animal model studies, indicate that higher oxidation states (ferryl) of heme proteins and their associated radicals play a major role in the mechanisms of pathology.
Reeder
Brandon J
BJ
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex, UK. reedb@essex.ac.uk
Svistunenko
Dimitri A
DA
Cooper
Christopher E
CE
Wilson
Michael T
MT
D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004195:Disease Models, Animal; D005609:Free Radicals; D006418:Heme / Q000737:chemistry; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007874:Leghemoglobin / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D009211:Myoglobin / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D013053:Spectrophotometry; D013696:Temperature
D003432:Cross-Linking Reagents; D005609:Free Radicals; D006454:Hemoglobins; D007874:Leghemoglobin; D009211:Myoglobin; D010545:Peroxides; C049375:perhydroxyl radical; D006418:Heme; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen