The redox activity of hemoglobins: from physiologic functions to pathologic mechanisms.
Pentacoordinate respiratory hemoproteins such as hemoglobin and myoglobin have evolved to supply cells with oxygen. However, these respiratory heme proteins are also known to function as redox enzymes, reacting with compounds such as nitric oxide and peroxides. The recent discoveries of hexacoordinate hemoglobins in vertebrates and nonsymbiotic plants suggest that the redox activity of globins is inherent to the molecule. The uncontrolled formation of radical species resulting from such redox chemistry on respiratory hemoproteins can lead to oxidative damage and cellular toxicity. In this review, we examine the functions of various globins and the mechanisms by which these globins act as redox enzymes under physiologic conditions. Evidence that redox reactions also occur under disease conditions, leading to pathologic complications, also is examined, focusing on recent discoveries showing that the ferryl oxidation state of these hemoproteins is present in these disease states in vivo. In addition, we review the latest advances in the understanding of globin redox mechanisms and how they might affect cellular signaling pathways and how they might be controlled therapeutically or, in the case of hemoglobin-based blood substitutes, through rational design.
Reeder
Brandon J
BJ
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex, England. reedb@essex.ac.uk
D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry; D000078842:Cytoglobin; D005914:Globins / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000078787:Neuroglobin; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D015398:Signal Transduction
D001802:Blood Substitutes; D000078842:Cytoglobin; D006420:Hemeproteins; D006454:Hemoglobins; D009211:Myoglobin; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D010545:Peroxides; D009569:Nitric Oxide; D006418:Heme; D005914:Globins; D010100:Oxygen