638 



XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



the bones, that it is more toxic than coproporphyrin, and that, in 

 acute porphyria porphobiHnogen, a dipyrrolic precursor of uropor- 

 phyrin is excreted. The facts that uroporphyrin is formed in the 

 normal megaloblastic hemopoiesis of the embryo, and occurs as a 

 physiologic product in the fox squirrel make it appear more likely 

 that the primary precursor of all porphyrins is a substance with the 

 acetic acid and propionic side chains which we find in uroporphyrin. 

 This was first suggested by Turner {2839), but without reference to 

 supporting evidence. Normally the primary precursor would undergo 

 decarboxylation to yield the precursors of coproporphyrin and proto- 

 porphyrin, while in porphyrias this decarboxylation is incomplete 

 owing to an inborn error of metabolism. It appears more reasonable 

 to explain the porphyrias in this way, than by assuming that a special 

 carboxylation process, not occurring under normal conditions, is at 

 work in the porphyrias.* 



COOH 



COOH 



(I) 



HC-COOH 



HOOC CH2 



(ID 



H3C CH2 



I I 



HC— CH 



I I 

 H2C— HC^ ^CO 



f N 



HOOC H 



H2C CHj 



HC— CH 



H2C— HC^ ^CO 



HOOC 



(III) 



Finally there is one important piece of evidence which has received 

 little attention. In 1931 Dakin and West {525) isolated from pow- 

 dered liver the tribasic acid ChHisOtN* H2O with a yield of up to 

 1%. Formula I was assumed for this acid, the |S-side chains being 

 formulated like those then assumed to be the side chains of uropor- 

 phyrin, but formula II with acetic and propionic acid side chains is 



* The decarboxylation of a precursor of coproporphyrin to one of protoporphyrin 

 is now supported by the fact that coproporphyrin is formed by Corynebacterium diph- 

 theriae when the synthesis of cytochrome b is inhibited by lack of iron (cf. Sections 6. 

 and 7.3.1.). Similarly, coproporphyrin is formed in yeast under conditions in which 

 the synthesis of the cytochromes appears to be deranged. 



