610 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



be discussed in Section 5. The problem of the mode of porphyrin 

 synthesis will be further discussed in later sections. 



3.2.3. Globin. The metabolism of globin is intimately connected 

 with the general protein metabolism of the body. Like iron and 

 unlike the prosthetic group, the protein part of the catabolized hemo- 

 globin is used once more in the synthesis of hemoglobin (Whipple 

 and co-workers, 1090,1951,2291;2293,2398,30^9,3051,3061-3063a). In 

 aplastic anemia hemoglobin-forming factors, probably building stones 

 of globin, are accumulated in the liver (304-9). There is a ready 

 exchange between protein reserve stores in the liver, plasma protein, 

 and the protein used for hemoglobin synthesis {305Ji.,3055). Whipple 

 speaks of a protein pool, and considers the plasma protein as a medium 

 of exchange, in physiologic equilibrium with red cell hemoglobin and 

 stroma protein. Even the starved anemic dog produces considerable 

 amounts of hemoglobin from tissue protein {523). A dog weighing 

 16 kg., which produces 60 g. hemoglobin per week on salmon-bread 

 diet, can produce up to 100 g. if protein and iron are added to the 

 diet. Plasma protein given intravenously is incorporated in hemo- 

 globin if iron is available. When both plasma protein and hemoglobin 

 are low, the protein synthesis is partitioned in the ratio of 2-4 g. 

 hemoglobin per g. plasma protein. While additional protein has no 

 effect on the copper deficiency anemia of rats (Pearson, Elvehjem, 

 Hart, 2130), a protein lack anemia in rats can be produced (Orten 

 and Orten, 208It). 



Individual amino acids. It has often been reported that individual 

 amino acids are of importance for hemopoiesis, but there is little 

 satisfactory evidence. 



Tryptophane has been claimed by several workers to be essential for 

 hemoglobin formation {33,1110,1133), but Alcock {37) found no evidence 

 that lack of tryptophane was able to produce anemia in rats or that trypto- 

 phane accelerated the recovery of rats from anemia produced by a milk 

 diet. There is no valid evidence to support the assumption that tryptophane 

 is required for the formation of the prosthetic group of hemoglobin. Thomas 

 {2798) found that the porphyrin content of the Harderian glands of adult or 

 growing rats was independent of tryptophane supply.* 



Drabkin and Miller {630,631) found that several amino acids, particularly 

 glutamic acid and arginine, cause recovery of milk-anemic rats fed additional 

 iron, but no copper, while other amino acids were found inactive. They 



* Cf. also Robscheit-Robbins, Miller, and Whipple (229^a), who found tryptophane 

 to favor the formation of plasma protein rather than of hemoglobin in doubly depleted 

 dogs, whereas arginine, lysine, and histidine favored hemoglobin formation. 



