REQUIREMENTS FOR HEMOGLOBIN SYNTHESIS 609 



1758,25JfJ!i.,30Jf9) and this is not due to its pyrrole content, but to the 

 fact that part of its iron is removed in the intestine (c/. Section 4.) 

 and that use is made of the amino acids of the globin part. The 

 small porphyrin content of the food is obviously insufficient for 

 hemoglobin synthesis. 



Claims that feeding porphyrins or chlorophyll increases hemoglobin forma- 

 tion have been made by Hughes and co-workers {136o) and by Kirkman 

 (1538), although the experiments of the last-mentioned worker actually give 

 very little support to his claim. Kohler, Elvehjem, and Hart {1562) found 

 that chlorophyll, protoporphyrin, and bilirubin did not increase hemoglobin 

 formation in rats made anemic by lack of copper, but supplied with iron. 

 Robscheit-Robbins and Whipple {2296) found that pyrrole compounds were 

 unable to increase hemoglobin formation in dogs made anemic by bleeding 

 and kept on standard salmon-bread diet. Zih {3180) also failed to observe 

 any effect of chlorophyll on hemoglobin formation in humans. 



Many workers (Brown, McMaster, Rous, Morawitz, Duesberg, 

 Heilmeyer, Witts, Watson, and Whipple) assumed that bilirubin or 

 other breakdown products of the prosthetic group of hemoglobin (the 

 "pyrrole body complex" of Whipple) could be retained in the body 

 and utilized for hemoglobin synthesis or even for bilirubin formation 

 {3045,3053; but cf. 2372). This was partly based on experimental 

 work of Brown, McMaster, and Rous {31^6) and Patek and Minot 

 (2117,2118), and was partly due to lack of distinction between re-util- 

 ization of the globin and of the prosthetic group (Whipple). The 

 later experiments of Whipple and his co-workers (516,1192,1193,1195, 

 1196,1584,1951,2548, cf. also Seyderhelm and Tammann, 2536) have 

 clearly shown that the protein and iron of catabolized hemoglobin 

 are carefully husbanded in the body and re-utilized for hemoglobin 

 synthesis, while the prosthetic group is quantitatively excreted as 

 bilirubin, even under conditions of severe anemia in dogs. These 

 experiments prove that the ability of the animal body to synthesize 

 the porphyrin nucleus is far in excess of its normal need. So far no 

 conditions have been discovered in which the synthesis of the por- 

 phyrin nucleus becomes the limiting factor of hemoglobin formation 

 (3061). From this it can be concluded that the actual precursors from 

 which the porphyrin ring is formed must be relatively simple com- 

 pounds, universally present in the animal body in large amounts. 

 This does not necessarily exclude the possibility that breakdown 

 products of the prosthetic group of hemoglobin, such as bilirubin, 

 may stimulate hemoglobin formation in an indirect way; this will 



