598 XII. HEMOGLOBIN CATABOLISM, II 



under which methemalbuminemia would be expected {cf. Section 

 3.4.2.); and where methemalbuminemia is accompanied by increased 

 porphyrin excretion, the nature of the porphyrin proves that it is 

 not derived from methemalbumin or hemoglobin {cf. above). Our 

 scepticism with regard to the theory of Rimington and Brownlee is 

 shared by Heubner {125Jt). 



An alternative hypothesis is that the aromatic amino compounds derange 

 hemoglobin breakdown in the liver, as perhaps the arsphenamines do. 



Finally, the possibility must be considered that the effect is on hemopoiesis 

 rather than on hemoglobin breakdown. Van Loon, Clark, and collaborators 

 (4-4S,1780) found that acetanilide and phenacetin cause a marked increase of 

 hemopoiesis in the bone marrow. They consider the reduced venous oxygen 

 saturation in hemiglobinemia a stimulant of erythropoiesis. On the other 

 hand, Watson and Spink (3004) found sulfonamides to cause a lowered color 

 index of the blood, indicative of interference with hemoglobin synthesis. 

 This will be further discussed in Chapter XIII. 



3.4.6. Porphyrin Formation by Hemoglobin Breakdown. Sum- 

 marizing the evidence discussed in Sections 3.4.2. to 3.4.5. one can 

 state that only in a few instances (some cases of liver disease and 

 toxic porphyrinurias caused by aromatic amino compounds) is por- 

 phyrin formation by hemoglobin breakdown likely and that even in 

 these it has not been proved. To these instances may be added the 

 porphyrinuria caused by methyl chloride for which another explana- 

 tion will be suggested in Chapter XIII. 



The term "hematoporphyrinuria" is, therefore, not only misleading 

 with regard to the chemical nature of the porphyrin in the urine, 

 but is also incorrect from a physiologic point of view since it implies 

 formation of porphyrin from hemoglobin. 



There can be no doubt that protoporphyrin can be formed in the 

 animal body by hemoglobin breakdown without bacterial action. 

 The protoporphyrin in bird egg shells and in the rat placenta {cf. 

 Section 3.2.6.) are certainly derived from hemoglobin, and Thomas 

 {2798) has shown that the damaged liver of the rat transforms 

 hemoglobin to porphyrin, probably again protoporphyrin. The proto- 

 porphyrin found by Thomas {2798) in chloroma and in myeloid 

 leukemia may also be derived from hemoglobin, although Thomas 

 came to the conclusion that it was synthesized in the cells of the 

 tumor {cf. Section 3.4.7.). There is at present no proof, however, 

 that coproporphyrin or uroporphyrin can be formed in hemoglobin 

 breakdown. 



