Oxidation of hemoglobin

Superoxide is formed (reaction 1) in the red blood cell by the auto-oxidation of hemoglobin to methemo-globin (approximately 3% of hemoglobin in human red blood cells has been calculated to auto-oxidize per day) in other tissues, it is formed by the action of enzymes such as cytochrome P450 reductase and xanthine oxidase. When stimulated by contact with bacteria, neutrophils exhibit a respiratory burst (see below) and produce superoxide in a reaction catalyzed by NADPH oxidase (reaction 2). Superoxide spontaneously dismu-tates to form H2O2 and O2 however, the rate of this same reaction is speeded up tremendously by the action of the enzyme superoxide dismutase (reaction 3). Hydrogen peroxide is subject to a number of fates. The enzyme catalase, present in many types of cells, converts... 

Labrude P, Chaillot B, Vigneron C. Influence of physical conditions on the oxidation of hemoglobin during freeze-drying. Cryobiology 1984 21 33. 

The hydrolysis of some amides may be catalyzed by a liver microsomal carboxyl esterase, as is the case with phenacetin (Fig. 4.44). Hydrolysis of the acetylamino group, resulting in deacetylation, is known to be important in the toxicity of a number of compounds. For example, the deacetylated metabolites of phenacetin are thought to be responsible for its toxicity, the oxidation of hemoglobin to methemoglobin. This toxic effect occasionally occurs in subjects taking therapeutic doses of the drug and who have a deficiency in the normal pathway of metabolism of phenacetin to paracetamol. Consequently, more phenacetin is metabolized by deacetylation and subsequent oxidation to toxic metabolites (chap. 5, Fig. 24). 

Hydroxyprimaquine (Fig. 7.46) will produce ROS in red cells, causing oxidative injury to the cytoskeleton and the oxidation of hemoglobin. The oxidized hemoglobin will bind via disulfide bridges to cytoskeletal proteins (seen as Heinz bodies under the microscope). This and other damages to the red cell lead to their removal by the spleen, and therefore anemia develops. 5-Hydroxyprimaquine also causes a depletion of GSH and the formation of GSS-protein conjugates. This metabolite is considerably more potent than 6-methoxy-8-hydroxylaminoquinoline. 

MB can undergo oxidative -> electropolymerization resulting in a poly(methylene blue) film on Au or Pt electrodes. The structure of MB is preserved in PMB, and hence it shows the same catalytic activity, e.g., towards the oxidation of - hemoglobin as the monomer does. Refs. [i] HepelM, Janusz W (2000) Eletrochim Acta 45 3785 [ii] Svetli-cic V, Zutic V, Clavilier J, Chevalet J (1985) JElectroanal Chem 195 307 Zaitseva G, Gushikem Y, Ribeiro ES, Rosatto SS (2002) Electrochim Acta 1469 [Hi] Kertesz V, Bacskai J, Inzelt G (1996) Electrochim Acta 41 2877 [iv] Brett CMA, Inzelt G, Kertesz V (1999) Anal Chim Acta 385 119... 

When the taurine chloramine uptake rate exceeds the rate of NADPH-dependent regeneration of GSH, there is a net loss of cellular GSH level, causing protein-thiol oxidation, ATP loss, and disruption of cellular metabolism. Heme moieties are the other target of chloramine attack on cellular constituents. Oxidation of hemoglobin to methemoglobin (and other hemoproteins to their oxidized derivatives) occurs at 10-fold excess of chloramine taurine molar concentration compared... 

Several in vitro studies proved that treatment of intact erythrocytes with nitrites causes the oxidation of hemoglobin to methemoglobin by radical generation along with a decrease in reduced glutathione (GSH) level associated with erythrocyte membrane dysfunctions and namely altered cell ionic flux, lipid peroxidation, and perturbation of membrane transport (Batina et al 1990 May et al 2000). Nitrate/ nitrite-induced oxidation of biological molecules potentiates reactions, which interfere in the oxidative chain and which can affect some antioxidant systems. 

The hematopoietic system is affected by both short- and long-term arsenic exposure. Arsenic is known to cause a wide variety of hematological abnormalities like anemia, absolute neutropenia, leucopenia, thrombocytopenia, and relative eosinophilia - more common than absolute esino-philia, basophilic stippling, increased bone marrow vascularity, and rouleau formation (Rezuke et al, 1991). These effects may be due to a direct hemolytic or cytotoxic effect on the blood cells and a suppression of erythropoiesis. The mechanism of hemolysis involves depletion of intracellular GSH, resulting in the oxidation of hemoglobin (Saha et al, 1999). Arsenic exposure is also known to influence the activity of several enzymes of heme biosynthesis. Arsenic produces a decrease in ferrochelatase, and decrease in COPRO-OX and increase in hepatic 5-aminolevulinic acid synthetase activity (Woods and Southern, 1989). Subchronic... 

Hemoglobin Content Hemoglobin content is determined with the Sigma Drabkin solution Kit 525. The principle of the assay is based on the oxidation of hemoglobin to cyan-meta-hemoglobin which is detectable spectrophotometricaUy at 540 nm. 

Nitrites bind to hemoglobin causing oxidation of hemoglobin to methemoglobin, which is unable to transport oxygen. When methemoglobinemia exceeds 10-15%, cyanosis may become apparent. 

Alpoim MC, Geraides CF, Oliveira CR, Lima MC. Molecular mechanisms of chromium toxicity Oxidation of hemoglobin, Biochem Soc Trans 1995 23 241S. 

Brooks (28,29) showed that the oxidation of hemoglobin at pH 5.69 is first order in unoxidized hemoglobin and the first order velocity constant fcob,. is dependent on the oxygen pressure according to the complex function illustrated in Fig. 1A. Brooks summarized his results in the following rate equation ... 

Oxidation of hemoglobin to methemogiobin occurs within 30 minutes. If no response to treatment occurs within 30 minutes, an additional half-sized dose of intravenous sodium nitrite may be given. 

Doyle MP, Herman JG, Dykstra RL (1985) Autocatalytic oxidation of hemoglobin induced by nitrite activation and chemical inhibition. J Free Radic Biol Med 1 145-153... 

Doyle, M.P., D.M. LePoire, and R.A. Pickering (1985). Oxidation of hemoglobin and myoglobin by alkyl nitrites inhibition by oxygen. J. Biol. Chem. 256, 12399-12404. 

Poly(methylene blue), in which methylene blue entities are preserved [121,226-234], is a very good catalyst for the oxidation of hemoglobin. This property has been utilized in an amperometric sensor [121] (see Figs. 7.20 and 7.21). 

In addition to its effect on fat oxidation, salt also accelerates the oxidation of hemoglobin and myoglobin to the ferric form, whether or not fat is present. Coleman (1951) has summarized the rather extensive literature on this point. 

Niell and Hastings (1925) demonstrated more rapid conversion of hemoglobin to methemoglobin at intermediate rather than at very high or very low oxygen tensions. This was true not only for the spontaneous oxidation of laked blood corpuscles but also for the oxidation of hemoglobin catalyzed by unsaturated fats. 

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