Hemoglobin autoxidation

Richards, M.P. and Dettmann, M.A. Comparative analysis of different hemoglobins autoxidation, reaction with peroxide, and lipid oxidation. J. Agric. Food Chem. 51,3886-3891 (2003). 

Shikama K. 1998. The molecular mechanism of autoxidation for myoglobin and hemoglobin A venerable puzzle. Chem Rev 98 1357. 

H.P. Misra and I. Fridovich, Generation of superoxide radical during the autoxidation of hemoglobin. J. Biol. Chem. 247, 6960-6962 (1972). 

It has been proposed that a major source of oxygen radicals in sickle erythrocytes is mutant hemoglobin HbS. However, although HbS showed an accelerated autoxidation rate under in vitro conditions, its in vivo oxidative activity was not determined. Sheng et al. [401] suggested that the observed oxidation rate of HbS is exaggerated by adventitious iron. Dias-Da-Motta et al. [402] proposed that another source of enhanced superoxide production in sickle cells are monocytes in contrast, there is no difference in superoxide release by sickle... 

The autoxidation of bovine heart myoglobin and of shark hemoglobin were followed respectively by the decrease of the absorbance at 581 and at 430 nm. BESOD accelerated definitely the autoxidation of the myoglobin but only very... 

Of greatest interest are those compounds that attempt to model hemoglobin directly. Simple iron(II) porphyrins are readily autoxidized first to superoxo species, then to //-peroxo dimers and finally to /x-oxo dimers, as represented in equation (60). Bridge formation must be prevented if carrier properties are to be observed. This has been achieved by the use of low temperature and sterically hindered or immobilized iron(II) porphyrins. Irreversible oxidation is also hindered by the use of hydrophobic environments. In addition, model porphyrins should be five-coordinate to allow the ready binding of 02 this requires that one side should be protected with a hydrophobic structure. Attempts have also been made to investigate the cooperative effect by studying models in which different degrees of strain have been introduced. 

In chemistry, it is well known that O2 can be strongly bound to a ferrons iron porphyrin in solvents without any protein matrix however, the oxygenated states of most simple iron porphyrins are irreversibly converted into /r-oxodimers (eqnation3), PFe(III)-0-PFe(III), via peroxo and ferryl intermediates (eqnation 2). The /x-oxodimer is usually very stable in solvents, so it is sometimes called a thermodynamic sink. In addition, autoxidation of PFe(II)-02 to an inert ferric porphyrin easily occurs under aerobic conditions (equation 4). Thus, it is clear that the heme pockets of myoglobin and hemoglobin play an important role in protecting the 02-bound heme from dimerization and autoxidation. 

Table 1 O2 Binding and autoxidation for a series of myoglobins, hemoglobins, and synthetic models (20 °C, pH 7.0)...

Watkins, J.A. Kawanishi, S. Caughey, W.S. Autoxidation reactions of hemoglobin a free from other red cell components a minimal mechanism. Biochem. Biophys. Res. Commun. 1985,132 (2), 742-748. 

The most common dioxygen carriers of nature, the heme proteins hemoglobin and myoglobin, bind Oj in a characteristic structure. The Oj molecule binds to the metal atom through one of its atoms, and the M—O—O unit is angular in shape. Studies on small molecules that bind O2 in this way have concentrated on two classes of ligands, porphyrins and Schiff bases.In the first case, bulky superstructures are usually appended to the porphyrin ligand this superstructure inhibits autoxidation of the metal atom in the... 

Other reactions of hemoglobin also permit a free radical interpretation, notably the coupled oxidation with ascorbic acid by molecular 02 which yields choleglobin, but further discussion requires a full kinetic analysis. Even though the denaturation reactions described above have not been examined kinetically it is worth emphasizing that their chief features can be explained by the formation of 02- as in the mechanism advanced for the autoxidation. The liberation of an activated O2 molecule is no longer required—02 is the active oxygen. 

Kinetic studies of the autoxidation of hemoglobin and myoglobin do not favor intramolecular mechanisms involving reaction between separated groups on the protein molecule, but the form of the rate equations resembles that found when two valency states of a metal ion compete for the same radical intermediate. A free radical mechanism based on competition for the HO2 radical can be developed to account for the observed results. 

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