Carbon monoxide interaction with hemoglobin

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. 

The French physiologist Claude Bernard (1857) and the British physiologist Haldane (1895a) inferred that the toxicity of CO was caused by its interaction with hemoglobin. In his review of carbon monoxide, Lilienthal (1950) writes It has been said many times that the effect of CO on man may be attributed to two actions and, in essence, to these two actions alone (a) occupation of the Hb molecule by CO, with a resultant decrease in the O2 transport capacity of the blood and (b) alteration of 02Hb dissociation... 

Two examples of toxicity, where the target is known, are carbon monoxide, which interacts specifically with hemoglobin, and cyanide, which interacts specifically with the enzyme cytochrome a3 of the electron transport chain (see chap. 7). The toxic effects of these two compounds are a direct result of these interactions and, it is assumed, depend on the number of molecules of the toxic compound bound to the receptors. However, the final toxic effects involve cellular damage and death and also depend on other factors. Other examples where specific receptors are known to be involved in the mediation of toxic effects are microsomal enzyme inducers, organophosphorus compounds, and peroxisomal proliferators (see chaps. 5-7). 

However, the mathematics describes an idealized situation, and the real situation in vivo may not be so straightforward. For example, with carbon monoxide, as already indicated, the toxicity involves a reversible interaction with a receptor, the protein molecule hemoglobin (see chap. 7 for further details of this example). This interaction will certainly be proportional to the concentration of carbon monoxide in the red blood cell. However, in vivo about 50% occupancy or 50% carboxyhemoglobin may be sufficient for the final toxic effect, which is cellular hypoxia and lethality. Duration of exposure is also a factor here because hypoxic cell death is not an instantaneous response. This time-exposure index is also very important in considerations of chemical carcinogenesis. 

P. Politzer, A charge-transfer interpretation of the interactions of hemoglobin with oxygen and carbon monoxide. Biochim. Biophys. Acta 153, 799-803 (1968)... 

The dioxygen (O molecule serves as an acceptor when interacting with the Fe center of the protein porphyrin structure therefore, other n acceptor molecules such as nitric oxide (NO), carbon monoxide (CO), cyanide (CN ), isocyanide (R-NC), azide ion (Nj ), and thiocyanate (SCN ) can stop hemoglobin from properly capturing and transporting oxygen ultimately leading to asphyxiation and death. 

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