326 VII. COMPARATIVE BIOCHEMISTRY OF HEMOGLOBINS 



environmental changes which it cannot avoid. It is determined by 

 several factors: the kinetics of the pigment, the concentration of the 

 pigment in the circulation, the circulation rate, and the velocity of 

 diffusion of gaseous oxygen across cell walls. 



The oxygen-carrying pigments may differ in prosthetic group, in 

 protein, and in microenvironment. These factors operate together 

 to produce variations in the reaction between oxygen and the carrier. 

 It is by means of these variations that the reaction is adapted to the 

 variety of conditions met with in living organisms. 



8.2. Mechanisms 



8.2.1. Variation of the Heme. A heme which differs from protoheme IX 

 is found only in the chlorocruorin in the blood of the Sabellid worms. The 

 oxygen capacity of Spirographis blood is only 9 volumes per cent {119, p. 79). 

 This is probably due to the fact that the pigment is extracellular rather than 

 to the structure of the prosthetic group. Since this pigment is found only 

 in a small group of worms which live in the same type of environment as do 

 others containing erythrocruorins with protoheme IX as prosthetic group, 

 the peculiarity does not appear to be of adaptive importance and may be an 

 evolutionary relic. 



8.2.2. Variation of the Protein. A protein suitable for the formation of an 

 oxygen carrier must be able to combine with heme, giving a compound able 

 to bind oxygen without oxidation of the iron or catalytic destruction of the 

 heme or the protein. This condition is fulfilled in its simplest form in the 

 pigments of the type of myohemoglobin, which consist m vitro of single 

 Hiifner units. Even in its simplest form (which is not necessarily the most 

 primitive), variation in the structure of protein affects the affinity of the 

 pigment for oxygen. 



On present hypothesis of hemoglobin structure, such simple pigments have 

 a dissociation curve of hyperbolic shape; such a dissociation curve is dis- 

 advantageous for some oxygen carriers (Section 9.1.). In addition the attain- 

 ment of high oxygen capacities with such pigments and their relatively small 

 size would render necessary impermeable cell walls, since the high concen- 

 tration of pigment required would entail a high osmotic pressure. 



8.2.3. Variation of Microenvironment. The ability to form macromole- 

 cules is of great functional importance. In these macromolccules the com- 

 bination with other substances, e.g., salts, water, and stromatin, may not 

 only solve the problem of the osmotic pressure and the problems raised by 

 the ease of diffusion of the smaller molecules, but also may protect the 

 molecule from destruction by reducing substances in the presence of oxygen. 

 In the macromolecule, moreover, the phenomenon of heme-heme interaction 

 appears, enabling the hyperbolic dissociation curve of the Hiifner unit to be 

 transformed into the sigmoid dissociation curve of hemoglobin. On the one 

 hand, this gives the pigment a still greater power of functional adaptation 



