260 VI. HEMOGLOBIN 



5. HEMOGLOBIN EQUILIBRIA 



5.1. Equilibria in Simple Systems — Interaction 

 between Hemes 



5.1.1. Introduction. Toward the end of the last century, knowl- 

 edge of the reactions of hemoglobin had advanced sufficiently to be 

 applied to many of the problems which technological progress had 

 raised for human physiology. These included the toxic effects of 

 carbon monoxide and other gases and the investigation of the physio- 

 logical stresses involved in work under extremes of atmospheric 

 pressure. The history of these investigations may be found in the 

 works of Bert C?^9), J. S. Haldane {1101), Barcroft {lU) and 

 Henderson {121^7). They accelerated the improvement of many 

 valuable experimental methods, such as the modern technique of gas 

 analysis and the microrespirometer, and led as well to many advances 

 in spectroscopy. On the theoretical side, the need for quantitative 

 data stimulated the rapid application of physical chemistry to this 

 branch of physiology. Empirical answers were given to many prac- 

 tical problems far more rapidly than understanding was reached of 

 the basic mechanism of the reaction. At the present time, indeed, 

 the elucidation of the behavior of hemoglobin, the most thoroughly 

 investigated protein, is probably of less importance for respiratory 

 physiology than for the general advance of protein and enzyme 

 chemistry. 



Attempts at theoretical interpretations of the equilibrium between 

 oxygen and hemoglobin have arisen alongside the experimental identi- 

 fication of the factors which influence the reactions. These may be 

 divided into those factors which concern the structure of the hemo- 

 globin, and those which concern the environment in which the equi- 

 librium is measured. The former are dealt with in Chapter VII. 



The environment influences the affinity of a given sample of hemo- 

 globin for oxygen according to: {1) Temperature. Increase of tem- 

 perature diminishes the affinity and vice versa. {2) ;jH. The affinity 

 is a minimum at about pH 6.1; on either side of this pH value, it 

 increases, {3) Ionic strength. The affinity is a maximum at zero 

 ionic strength. (^) Specific ion effects are at present little investi- 

 gated. (5) Concentration of hemoglobin. The more dilute the 

 solution of hemoglobin, the greater the affinity. 



The situation is further complicated by the presence of the four 

 hemes in the hemoglobin molecule, which enables the affinity of 



