PORPHYRIN FROM AROMATIC AMINO COMPOUNDS 597 



have been noted, however; thus aspirin does not form hemiglobin, 

 but causes porphyrinuria. The porphyrin was found to be copro- 

 porphyrin III, but this is of no great evidential value since the 

 normal urinary porphyrin in rats may also be coproporphyrin III, 

 but is not derived from hemoglobin breakdown (Thomas, 2798). 



An increased fecal porphyrin excretion after injection of hematin 

 in man, monkeys, and rabbits has also been mentioned, without full 

 experimental data, by Rimington and Hemmings (2265,2271); the 

 fecal porphyrin was found to consist of proto- and coproporphyrin. 

 Rimington points out the repeated observations of "hematinemia" 

 together with porphyrinuria; but in hemolytic anemia as well as in 

 pernicious anemia, for which this is true, the porphyrin is of type I. 

 It would appear a matter of interest to establish the nature of the 

 excess coproporphyrin in the feces, which ought to be of type III, 

 while so far only type I has been found in normal feces. 



Rimington and, independently, Brownlee conclude that the aro- 

 matic amines, or substances derived from them, probably amino- 

 phenols, cause a deranged hemoglobin catabolism, in which hemo- 

 globin, as a ferric hematin compound, is not converted to bile pigment 

 but to porphyrin. 



Quantitatively the porphyrin formation is on a small scale, and it 

 is therefore certainly an exaggeration when Brownlee states: "Where 

 hemoglobin is oxidised to methaemoglobin, the normal conversion 

 into bilirubin cannot occur, but is replaced by degradation to copro- 

 porphyrin III." 



No chemical explanation for the formation of porphyrin from hemoglobin 

 is apparent. In ritrn, ferrous heme compounds are transformed far more 

 readily than ferric to porphyrin. Hem/globin can thus hardly be considered 

 a direct precursor of porphyrin. Rimington and Brownlee postulate an inhi- 

 bition of bile pigment formation by hem/globin formation, but so far there 

 is no evidence for this. On the contrary, van Loon, Clark, and collaborators 

 (4-^J780) found that acetanilide and phenacetin increase .serum bilirubin, 

 and urobilin excretion is increased by sulfonamides (1007,3004). Many 

 hem/globin-forming substances also cause irreversible breakdown of hemo- 

 globin to bile pigment, and we have met hem/globin as an intermediate of 

 choleglobin and biliverdin formation from hemoglobin (cf. Chapter X, 

 Section 4.4.1.). 



It is true that methemalbumin and hematin are transformed very 

 slowly to bile pigment, if at all. There is, however, no relationship 

 between hemiglobinemia and methemalbuminemia; there is no reli- 

 able ev^idence for increa.se of porphyrin formation under all conditions 



