PHARMACOLOGY AND TOXICOLOGY OF PORPHYRINS 599 



The mode of the transformation of hemoglobin to protoporphyrin is not 

 yet fully understood. Thomas (2798) believes that a hematin c-like compound 

 is an intermediate of porphyrin formation, since its iron is more readily 

 removed by acid than that of protohematin. This hypothesis is unlikely for 

 several reasons. First, the mode of formation of hematin c is not a simple 

 reduction followed by oxidation as Thomas assumed, but involves irreversible 

 changes of the side chains and, in some instances, also of the nucleus; in 

 these changes the dithionite (used by Thomas as reducer) is involved. Second, 

 the porphyrin obtainable from hematins c is ether insoluble; no transforma- 

 tion of porphyrin c to protoporphyrin in the body has been demonstrated, 

 nor is it a reaction likely to occur. Third, ferrous heme compounds yield 

 their iron quite as readily as hematins c; their formation in vivo, particularly 

 in anoxic necrotic tissue, is to be expected. In vitro an unphysiologically low 

 pH is required for the removal of the iron, but in the body the reaction is 

 probably facilitated by chelating compounds which bind the iron in complex 

 form (cf. the formation of biliverdin from choleglobin with ascorbic acid. 

 Chapter X). 



3.4.7. Porphyrin Formation from Other Hematin Compounds. 



There is little evidence in favor of the assumption that porphyrin is 

 derived from myohemoglobin. Fischer, who in earlier papers sup- 

 ported this assumption, later abandoned it {790). Weiss {3022) and 

 Vannotti {28J^7,28i8) believe it to be supported by the involvement 

 of muscles in acute porphyria; and Vannotti {28I^7,28J^8) found por- 

 phyrinuria in a case of myositis, with porphyrin in heart muscle 

 cells, kidneys, and bones, but not in the marrow. As we have seen 

 above, the chemical findings in acute porphyria do not support this 

 hypothesis. 



Porphyrin formation from respiratory enzymes has also been 

 assumed {599,1004,1J^74,2798,2908), but there is no real evidence in 

 its favor {1516). We have mentioned that the porphyrin of yeast is 

 certainly not derived from its cytochrome since it is mainly of type I. 

 Thomas noted that cytochrome c .injected intradermally was con- 

 verted to a porphyrin, but the porphyrin was ether insoluble. 



The presence of protoporphyrin in chloroma or myeloid leukemia 

 has been explained by Thomas {2798) as due to a disturbance of 

 peroxidase synthesis. While the cells from which the tumor is derived 

 are rich in peroxidase, the tumor contains remarkably little, and 

 Thomas assumes a hyperactivity of the synthesis of porphyrin 

 normally used for peroxidase synthesis. 



3.5. Pharmacology and Toxicology of Porphyrins 

 3.5.1. Photosensitization. If animals after injection of porphyrin 

 solutions, or animals and patients suffering from chronic porphyria, 



