MINERALS 619 



Two different copper protein compounds, hemocuprein and hepato- 

 cuprein, have been isolated from erythrocytes and liver by Mann and Keilin 

 {1866), but there is at present no evidence for their physiologic activity.* 

 Hemocuprein completely accounts for the copper in the erythrocytes. 

 Tompsett {2815) had suggested that the copper in the red cell may be present 

 in the form of a mercaptide of glutathione. Elvehjem and co-workers {2180, 

 2Jf80) were unable, however, to detect clear-cut relations between the effect 

 of copper on hemopoiesis and the glutathione content of the erythrocytes. 



Cobalt. The causation of anemia in sheep by cobalt deficiency 

 was discovered by Filmer {961) and Marston {1877) in Australia, 

 and is also found in cattle {2014.); cf. the reviews of HuflPmann and 

 Duncan {1360) and Russell {2398). 



Horses are not affected by it. Recently it has been found (c/. 1799) that 

 cobalt prevents or cures the disease only if given by mouth and not if injected 

 parenterally. It has been suggested that the metal acts on the bacteria of 

 the rumen rather than on the host. In milk-anemic rats Frost and Elvehjem 

 {957) found cobalt, in addition to iron and copper, necessary for the full 

 restoration of hemoglobin, although under certain conditions an excess of 

 cobalt had an opposite effect in young dogs (Elvehjem and co-workers, 

 956,1820); it has also been found that cobalt stimulates hemopoiesis in the 

 salamander {^28). 



Excess of cobalt causes a polycythemia and erythremia which was 

 discovered by Waltner and Waltner {2915) and has been confirmed 

 by many workers with different animals. It is accompanied by hyper- 

 plasia of the bone marrow and reticulocytosis. Cobalt certainly does 

 not cause a decrease of hemoglobin catabolism, the blood bilirubin 

 being higher than normal {2087), at least in the initial stages; in the 

 later stages decreased phagocytosis has been observed {544, cf. also 

 U72). 



The way in which the metal produces the polycythemia is still 

 unknown. Since dilator drugs such as choline abolish it, Orten 

 {2087) believed that cobalt caused primarily a vasoconstriction in 

 the bone marrow with resulting anoxia. Barron and Barron {177) and 

 Davis {538,539), on the other hand, came to the conclusion that 

 cobalt acted upon the respiration and maturation of the immature 

 red cells {cf. Section 3.3.2.). Warren, Schubmehl, and Wood {2963) 

 were unable to confirm either of these hypotheses and assume an 

 action on the liver. Kato and lob {1472) found no mobilization of 

 liver iron by cobalt, but observed an increase of the nonhemoglobin 



* (/., however, Holmberg and Laurell {1325a). 



