PORPHYRINS AS INTERMEDIATES AND BY-PRODUCTS 629 



response {60 Jf). In pernicious anemia the fecal coproporphyrin I 

 excretion is high in relapse and (hiring the response to hver therapy, 

 but dechnes sharply after the reticulocyte crisis to remain normal in 

 remission; it is found to be roughly parallel to the degree of hemo- 

 poiesis (Dobriner and co-workers, 601,603,60^: Watson, 2976). In 

 refractory anemias, too, fecal coproporphyrin I excretion is found to 

 be correlated with the state of the bone marrow as revealed by biopsy 

 (604). Libowitzky and Scheid {1733) found increased hemopoietic 

 activity in febrile episodes of schizophrenia associated with increased 

 excretion of coproporphyrin I. 



In addition to this increase of porphyrin formation associated with a 

 general increase of hemopoiesis, there is, however, in other diseases evidence 

 of a more specific derangement. This is found, first, in chronic porphyria, 

 in which large amounts of predominantly type I porphyrin are excreted 

 ($258), and, second, in acute porphyria, aplastic anemia, and porphyrinurias 

 caused by lead, methyl chloride, and perhaps also aromatic amino com- 

 pounds in which there is increased formation of tj'pe III porphyrin. 



Duesberg {638) and later Rimington {2259; cf. also Vannotti, 28^9) 

 explained the increased excretion of coproporphyrin in lead intoxication by 

 assuming that the combination of iron and protoporphyrin in the immature 

 cell was inhibited and that the increased protoporphyrin in the blood was 

 ultimately excreted as coproporphyrin. In addition the lead inhibited 

 hemopoiesis. 



Against this theory Kench, Gillam, and Lane {1515) have raised several 

 objections. First, they found the porphyrin formation much too small to 

 account for the anemia and found no constant relationship between the 

 degree of anemia and porphyrin excretion. This is certainly correct, but is 

 no argument against the hypothesis of Duesberg and Rimington, unless the 

 assumption is made that the inhibition of hemopoiesis by lead is solely due 

 to the inhibition of iron incorporation {cf. Section 8. "2. ^2.). Second, they find 

 no correlation between stippled cells and porphyrin excretion. Since the 

 fluorescytes and not the stippled cells are the porphyrin-containing cells, 

 this is not surprising. Third, they do not find the constant relationship 

 between protoporphyrin content of the blood and coproporphyrin excretion, 

 which might be expected were the coproporphyrin III derived from the 

 protoporphyrin. There is no evidence {cf. Chapter XII) that protoporphj'rin 

 IX can be transformed in vivo to coproporphyrin III, and an alternative 

 explanation for its formation in lead intoxication as well as in other con- 

 ditions in which hemopoiesis is inhibited will be given in Section 8. 



The increase of coproporphyrin excretion in infections, which had been 

 explained by Schreus {2465) as due to increased hemoglobin breakdown, is 

 also due to inhibited hemoglobin synthesis {2862; cf. also Section 4.3.). 



It is now generally agreed that the protoporphyrin in the erythro- 

 cytes is formed as an intermediate of hemoglobin synthesis. The 



