Carbon monoxide-hemoglobin reactions

Hemoglobin (Hb) binds to both oxygen and carbon monoxide. When tiie carbon monoxide replaces the oxygen in an organism, the following reaction occurs ... 

Unfortunately, hemoglobin forms a complex with carbon monoxide that is considerably more stable than oxyhemoglobin. The equilibrium constant for the reaction... 

Carbon monoxide seriously impedes transport of oxygen. The deadly effect of inhaled CO results from its reaction with hemoglobin. A CO molecule is almost the same size and shape as O2, so it fits into the binding pocket of the hemoglobin molecule. In addition, the carbon atom of CO forms a stronger bond to than does O2. Under... 

Hydroxyurea reacts with oxy, deoxy and metHb in vitro to form iron nitrosyl hemoglobin (HbNO) and transfers NO to 2-6% of the iron heme groups [115]. Trapping studies using cyanide and carbon monoxide indicate that hydroxyurea oxidizes both oxy and deoxyHb to metHb and reduces metHb to deoxyHb specifically identifying the reaction of hydroxyurea and metHb as the critical reaction in the formation of HbNO from hydroxyurea [115]. Scheme 7.16 depicts the proposed mechanisms of N O and HbNO formation during the reaction of deoxy and metHb with hydroxyurea. Oxidation of hydroxyurea by metHb produces deoxyHb and the nitroxide radical (25,... 

The importance of reaction (13) was also shown with stimulated human neutrophils, which generate OJ and are thus able to lyse erythrocytes. This hemolysis was inhibited by exogenous (Cu,Zn)-SOD in contrast with the heat-denatured enzyme and with catalase. When hemoglobin in the erythrocytes was converted into methemoglobin by a nitrite treatment, SOD became ineffective, but exogenous catalase protected. The erythrocyte became resistant to hemolysis when treated with carbon monoxide, whereby the formation of methemoglobin was blocked and reaction (13) avoided... 

The first step in the two-step pathway, catalyzed by heme oxygenase (HO), converts heme to biliverdin, a linear (open) tetrapyrrole derivative (Fig. 22-25). The other products of the reaction are free Fe2+ and CO. The Fe2+ is quickly bound by ferritin. Carbon monoxide is a poison that binds to hemoglobin (see Box 5-1), and the production of CO by heme oxygenase ensures that, even in the absence of environmental exposure, about 1% of an individual s heme is complexed with CO. 

Of these reactions in which CO coordinates with the oxidized form of metals, the most important is the reaction with the iron atom in the hemoglobin of the blood, leading to carbon monoxide poisoning. This iron atom is part of a ring structure similar to that in chlorophyll (Chap. 6), and it ordinarily takes part in the metabolic process by reversibly forming a Fe—0—0— compound with the oxygen of the air. If carbon monoxide... 

Spencer and Schaumburg 2000). Although the primary reaction of carbon monoxide is with hemoglobin, it also interacts with myoglobin, cytochromes, and metalloenzymes (e.g., cytochrome c oxidase and cytochrome P450) (WHO 1999). The health importance of these secondary reactions is not well understood. 

Carbon monoxide is toxic because it bonds much more strongly to the iron in hemoglobin (Hgb) than does 02. Consider the following reactions and approximate standard free energy changes ... 

Carbon monoxide, an odorless gas, has an affinity for hemoglobin that is 210 times that of oxygen. Thus, in the equilibrium reaction... 

Mechanisms regulating the reactions of human hemoglobin with oxygen and carbon monoxide, 1990, Ann. Rev. Phys., 52 125. 

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