608 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



marrow, which as we shall see exerts an influence on hemoglobin 

 formation. 



It is therefore not surprising that many substances are known 

 which exert an influence on hemoglobin formation, but that we know 

 very little about the way in which this action occurs. 



3.2. Building Stones of Hemoglobin 



3.2.1. Iron. It is obvious that iron is a building stone necessary for 

 the synthesis of hemoglobin. The iron treatment of anemias was 

 known to Hippocrates, but its practical use goes further back to 

 sympathetic magic, the iron of rusted arms being imbibed in order to 

 obtain its strength {1082). Iron is saved in the body with meticu- 

 lous care; very little of the iron set free in hemoglobin breakdown is 

 excreted (c/. Chapter XI, Section 10.2.), the remainder is stored and 

 used once more for hemoglobin synthesis. It is still claimed by some 

 workers that iron giv^en intravenously or in the food, in addition to 

 being a building stone of hemoglobin, acts as a stimulus (c/. Section 

 4,3.). The absorption of iron from the intestine and its incorporation 

 in the hemoglobin molecule will be further discussed in Section 4. 



3.2.2. The Porphyrin Nucleus. Neither preformed porphyrin nor 

 pyrrole compounds are required for the synthesis of hemoglobin, and 

 the potentialities of most organisms for synthesizing porphyrins are 

 far in excess of the requirements. Lwoff and Lwoff (1789-1793) have 

 discovered that most trypanosomes, some flagellates, and bacteria of 

 the Hemophilus influenzae type require protohematin as growth sub- 

 stance for the synthesis of their respiratory ferment. This cannot be 

 replaced by other blood or chlorophyll hematins, not even by cyto- 

 chrome c. Granick and Gilder {1035) have shown that these organ- 

 isms can combine iron with protoporphyrin, but lack the power of 

 synthesizing the latter. Other porphyrins inhibit the synthesis of the 

 respiratory ferments competitively, while porphyrin esters are neither 

 useful, nor inhibitory. Many other microorganisms are, however, 

 able to synthesize porphyrins and respiratory heraatin enzymes (c/. 

 Section 6.). 



In mammals hematin in the food is useless as a source of the por- 

 phyrin nucleus of hemoglobin and is a poor source of iron. This was 

 observed in 1895 by Cloetta {^57) and confirmed by many workers 

 {677,680,681,12574313,1758,3056). Only 10-25% of hemoglobin 

 given by mouth is used for the formation of new hemoglobin (284, 



