PORPHYRIN IN LIVER DISEASES AND PORPHYRIA 595 



Section 3.3. .5.). Their hypothesis has been supported by experiments of 

 Thomas {2798). Not only was the total porphyrin excretion of rats increased 

 by damaging the liver with manganese chloride or phosphorus, but in such 

 animals it could be further increased by intravenous injection of hemoglobin, 

 which left the porphyrin excretion of normal animals unaltered. The por- 

 phyrin metabolism of the rat differs, however, from that in men in that most 

 of its excretory porphyrin is protoporphyrin, not coproporphyrin. 



The porphyrin in the majority of human liver diseases cannot be 

 derived from hemoglobin breakdown, since it is coproporphyrin I. 

 Only in a few cases of alcoholic cirrhosis or after salvarsan, where 

 coproporphyrin III has been found, can the mechanism assumed by 

 Schreus and Thomas be at work. 



The investigations on the isomeride type of porphyrins have thus 

 restricted to a few diseases the possibility of assuming that porphyrin 

 is formed from hemoglobin, these being a few cases of liver disease, 

 aplastic anemia, acute porphyrias, and particularly toxic porphyri- 

 nurias. There are, however, other reasons for rejecting the theory 

 even in the majority of these diseases. 



It appears improbable that porphyrin formation in aplastic anemia 

 can be due to hemoglobin breakdown, since here it is the hemopoiesis 

 which is affected. In acute porphyria, the nature of the breakdown 

 products makes much more likely their formation by faulty hemo- 

 globin synthesis than by faulty breakdown (c/. Chapter XIII). If 

 the latter were correct, one would have to assume a special carboxy- 

 lation of protoporphyrin to uroporphyrin combined with decomposi- 

 tion of a tetrapyrrolic to a dipyrrolic compound (porphobilinogen). 

 Porphobilinogen has occasionally been mistaken for urobilinogen, 

 since it also gives the Ehrlich aldehyde reaction, and the presumptive 

 formation of urobilinogen has been taken as evidence of increased 

 hemoglobin breakdown. On the other hand, Rau {2213) has claimed 

 that urobilinogen is low where porphyrin is high, and conversely, and 

 has explained this on the basis of the theory of competition between 

 two modes of breakdown, which was first assumed by Garrod and 

 later by Hoesch and Carrie {1302). Again Rau's "urobilinogen" was 

 certainly porphobilinogen, and since this is the precursor of uropor- 

 phyrin in acute porphyria, the inverse ratio of porphyrin and por- 

 phobilinogen is only to be expected. If there were any competition 

 between porphyrin and bile pigment formation, it should be found 

 in chronic porphyria, where still larger amounts of porphyrin are 

 formed; in this disease, however, the anemia is slight and normal 

 bile pigment formation is observed. 



