594 XII. HEMOGLOBIN CATABOLISM, II 



hemolytic anemia or pernicious anemia. We have seen, however, in 

 Section 3.3.4. that in all these cases the coproporphyrin is of type I 

 and thus cannot be derived from hemoglobin breakdown. 



In the anemia of chronic infections both types I and III have been 

 found, but the porphyrin formation is due to derangement of hemo- 

 globin synthesis, not to hemoglobin breakdown (c/. Chapter XIII). 



If we collect some of the arguments brought forward in support of the 

 theory of porphyrin formation by hemoglobin breakdown, it is not diflBcult 

 to recognize their speciousness. An abnormally high bile pigment excretion 

 accompanying increased porphyrin excretion is accepted as evidence in 

 favor of the theory; but so is an exceptionally low bile pigment excretion, 

 which is assumed to be due to a competition between bile pigment and 

 porphyrin formation from hemoglobin (Hoesch and Carrie, 1302). Increased 

 hemoglobin breakdown is usually accompanied by increased hemopoiesis 

 and the latter, not the hemoglobin breakdown, causes the increased porphyrin 

 formation in hemolytic anemia or after phenylhydrazine (ef. Chapter XIII). 

 Evidence in favor of porphyrin formation by hemoglobin breakdown, derived 

 from parallel increase of bile pigment formation, is therefore of little value. 

 Herold {124.8) found the postnatal porphyrin excretion maximal at the third 

 day of life, together with the peak of bilirubin excretion, but again the 

 coproporphyrin is probably of type I {cf. Waldenstrom, 2908). The por- 

 phyrin of the chick embryo is formed during a stage at which little hemo- 

 globin and probably no bile pigment is present and can hardly be formed by 

 hemoglobin breakdown (Sch0nheyder, 2458) ; in the frequently quoted paper 

 of Sendju (2530), bile pigment formation in the chick embryo had been 

 studied by the entirely unreliable method of iodine titration. 



Schreus and Carrie (2469) claimed that intravenous injection of hemo- 

 globin caused porphyrinuria, but Duesberg (639) found no increase of 

 porphyrin excretion after hemoglobin injection or after hemolysis caused by 

 injection of distilled water or saponin. Thomas {2798) also failed to notice 

 any increase of total porphyrin excretion in the rat by hemoglobin injection 

 or intravascular hemolysis. Maugeri {1885) found the fecal protoporphyrin, 

 but not the urinary porphyrin, increased by hemolysis. 



3.4.3. Porphyrin in Liver Diseases and Porphyria. Liver diseases, par- 

 ticularly yellow atrophy and carcinoma, are frequently accompanied by an 

 increase of porphyrin excretion, not only in the urine {cf. Section 3.3.4.), 

 but also in the feces. The hypothesis of a disturbed hemoglobin breakdown 

 in the diseased liver leading to porphyrin formation has been supported 

 particularly by Schreus and Carrie {400,2470), their evidence being based 

 mainly on the demonstration of a decrease in erythrocyte numbers in the 

 blood parallel with an increase in porphyrin excretion. Most of their experi- 

 ments were carried out with arsphenamines (salvarsan) as a liver-damaging 

 agent. Their claim to have demonstrated the formation of protoporphyrin 

 from hemoglobin by the liver in vitro, is open to criticism; the porphyrin 

 may have been set free from reduced hemoglobin by the action of acid {cf. 



