Hemoglobin with carbon monoxide

PREFERENTIAL. Descriptive of the selectivity of action, either chemical or physiochemical. exhibited by a substance when in contact with two other substances it may be due either to chemical affinity or to surface phenomena. An example of a preferential chemical combination is that of hemoglobin with carbon monoxide, with which it unites 200 times as readily as it does with oxygen when expose to a mixture of the two. Such phenomena as adsorption, corrosion, and the wetting of dry powders by liquids are other examples,... 

Ainsworth and co-workers (1958) similarly studied the effect of p-chloromecuribenzoate on the rate constants l[ and for the combination of hemoglobin with carbon monoxide. They found that -chloromercuri-benzoate increases by a factor of 3 to 4 as well as the pH dependence of I l. On the other hand, p-chloromercuribenzoate decreases both the magnitude and pH dependence of No explanation of these striking results has yet been proposed. 

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

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... 

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. 

Therefore, when Pco = 1/220 XP02 the hemoglobin in the blood will be 50% saturated with carbon monoxide. Since air contains 21% oxygen, approximately 0.1% carbon monoxide will give this level of saturation. Hence, carbon monoxide is potentially very poisonous at low concentrations. The rate at which the arterial blood concentration of carbon monoxide reaches an equilibrium with the alveolar concentration will depend on other factors such as exercise and the efficiency of the lungs. Other factors will also affect the course of the poisoning. 

Carbon monoxide, like cyanide, poisons by combining with the heme of both cytochrome oxidase and hemoglobin (the Fe forms). This may be treated with hyperbaric oxygen, which competes with carbon monoxide for the hemoglobin, in addition to delivering to the tissues oxygen dissolved in the plasma. 

The absorbance change with carbon monoxide hemoglobin (HbCO) is demonstrated in Fig. 13 as a result obtained by Noe et al.57). In this experiment a modelocked Nd glass laser at 530 nm (6 ps) was applied as excitation source. The data were displayed in the form AA, change in absorbance between excitation and no excitation, versus time (Fig. 13). 

C. Oxygen (100%) is indicated for patients with carbon monoxide poisoning, to increase the conversion of carboxyhemoglobin and carboxymyoglobin to hemoglobin and myoglobin, and to increase oxygen saturation of the plasma and subsequent delivery to tissues. 

Ohe, M., Kajita, A. (1980) Changes in pka values of individual histidine-residues of human-hemoglobin upon reaction with carbon-monoxide. Biochemistry, 19 (19), 4443 450. 

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