DOUGLAS M. SURGENOR 



by the metal-combining protein. A similar reaction has been 

 shown to occur in vivo in animals with experimentally produced 

 hypoxia. On the basis of these and other observations, they have 

 suggested that the reverse reaction, transfer of iron from metal- 

 combining protein to ferritin with ferrous iron as the intermedi- 

 ate, may constitute the physiological mechanism for unloading 

 circulating plasma iron in the bone marrow. 



Distinctly different mechanisms appear to be responsible 

 for the transport of copper and zinc. In neither case is there an 

 analogy with that of iron. A blue copper-containing protein, 

 caeruloplasmin (17), has been isolated from plasma but the metal 

 appears to be an integral part of the molecule; it is not dis- 

 sociated by reduction and can be freed only by denaturing the 

 protein. Caeruloplasmin does not appear to be identical with, 

 but may be related to, hemocuprein, the copper protein of red 

 cells. The plasma level of caeruloplasmin is markedly reduced 

 in Wilson's disease, a serious congenital disease characterized by 

 marked neurological changes; however, the protein deficiency 

 does not appear to be the primary etiologic factor. 



Plasma contains significant amounts of zinc, of the order of 

 2 X 10~^ molar, which is intimately associated with one or more 

 proteins, as revealed by its behavior during fractionation and by 

 its failure of removal by cation-exchange resins under conditions 

 where added zinc is quantitatively removed. Some preliminary 

 studies with radioactive Zn^^-labeled plasma suggested that at 

 acid reactions, near /?H 5, the physiological zinc began to be 

 exchangeable. No zinc-containing proteins have been isolated 

 in pure form from plasma; however, since plasma is known to 

 contain trace amounts of certain peptidases, a group of enzymes 

 often found to be zinc-activated, it is likely that at least a part 

 of the plasma zinc is associated with these enzymes. Like copper, 

 zinc is found in the red cells as a constituent of carbonic anhy- 

 drase; it is also an important constituent of white cells. 



The incompatibility of most free lipids with the aqueous 

 environment of the body demands an unusually specialized 

 vehicle for their transport; the lipoproteins provide this mecha- 



656 



