BLOOD 



efficient utilization of the red cell compartment in its round trip 

 through the circulatory network. As we shall see, certain features 

 of these transformations are encountered in other systems. 



The transport of iron in the plasma bears many similarities 

 to the oxygen transport mechanism. A specific plasma protein, 

 the /3i-metal combining protein (34), possesses two unique and 

 apparently identical sites which combine with iron in the ferric 

 state; the resultant complex is salmon pink in color, reminiscent 

 of the iron complexes of aspergillic acid and related compounds 

 (13). The affinity of the protein for iron is such that within the 

 range of the binding capacity, the concentration of free, or 

 unbound, iron in the plasma is of the order of 10~^ molar or less. 

 Clinical studies (8) have confirmed these findings and have 

 established that the metal combining protein provides the 

 means for physiological transport of plasma iron. The protein 

 also reacts with copper, although less tightly than with iron, but 

 despite the fact that the protein is normally only partially satu- 

 rated with iron in venous blood, it does not appear to contribute 

 to the physiological transport of copper. 



Unlike oxygen, it seems improbable that unloading of iron 

 is achieved simply by reversal of the binding reaction. Since 

 the chemical equilibrium is so preponderantly in favor of the 

 metal-protein complex, dissociation of ferric iron would take 

 place only in the presence of an acceptor substance of higher 

 affinity for the metal than that of the plasma protein. This 

 reaction can be operated in vitro, but at a very slow rate. Al- 

 ternatively, since the affinity of the protein is /'H-dependent, 

 the iron is released upon acidification of the system, but only at 

 reactions more acid than would be encountered in the tissues. 

 The most likely unloading mechanism involves the reduction of 

 the iron to the ferrous state. This reaction proceeds in vitro at 

 neutral pH in the presence of a suitable reducing system (10). 

 Recently, Mazur, Baez, and Shorr (24) have found that a small 

 fraction of the iron in ferritin is reduced to the ferrous state under 

 anaerobic conditions or by treatment of ferritin with mild 

 reducing agents. This ferrous iron is then available for binding 



655 



