618 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



copper acts on hemoglobin synthesis. This is supported by several 

 observations. In many instances a decrease of the hemoglobin content 

 of the blood is accompanied by an increase of the copper ^content of 

 the plasma, and conversely an increase of hemoglobin by a decrease 

 of plasma copper {2]^02,2Jt.0If,2I^09). If hemopoiesis is stimulated 

 by hemorrhage or phenylhydrazine, the iron content of the plasma 

 decreases while the copper content increases (Sachs and co-workers, 

 2W6; Heilmeyer, 1222; cf. Chapter XI, Section 10.3.2.). If the 

 primary effect of copper were on the mobilization of iron in the liver, 

 a high plasma iron should be expected. Normally plasma contains 

 0.10 to 0.13 mg. copper per 100 ml. The low copper content of fetal 

 plasma and the high copper content of the fetal liver is attributed by 

 Sachs and co-workers {2Jf.04-) to the fact that in the fetus hemopoiesis 

 proceeds in the liver rather than in the bone marrow; after birth the 

 blood hemoglobin decreases, while the copper content of the plasma 

 rises. 



Copp and Greenberg (Ji.89) found that copper increases the rate of 

 utilization of radioactive iron in the bone marrow. Schultze and 

 Simmons {24S4), studying the absorption of radioactive Cu^ in 

 copper-deficient rats, found most of it to be retained in the kidney 

 and liver, while less than 0.1 mg. entered the bone marrow in 24 

 hours. Nevertheless, a great increase of its cytochrome oxidasa^ 

 content could be observed, together with increased hemopoiesis 

 (McCoy and Schultze, 180^). Copper isnecessary for the maintenance. _ 

 and formation of cytochrome oxidase, and also of cytochrome a, in 

 rat liver and heart (Cohen and Elvehjem, 4^59 ; Schultze, 24-75). The 

 cytochrome oxidase content of the bone marrow as well as the rate 

 of hemopoiesis is higher in young rats, and is increased by low oxygen 

 pressure or in recovery from severe anemia if copper is available. 



It is not clear, however, whether copper acts directly on hemoglobin 

 synthesis, or affects this only indirectly by its effect on the synthesis 

 of the respiratory ferment. Cohen and Elvehjem (459) found that 

 the synthesis of cytochrome a in the liver was affected by a degree 

 of copper deficiency, which did not seriously affect hemopoiesis, and 

 Schultze (2477) observed that the increase of the oxidase in the bone 

 marrow by copper preceded the reticulocytosis; on the other hand 

 Schultze (2475) found the synthesis of hemoglobin more sensitive 

 to lack of copper than that of the respiratory ferment in the bone 

 marrow. 



