IMPORTANCE OF BILIVERDIN 505 



clinical observations of Schottmiiller (2462), Schumm (2^90), and 

 Watson {2989) failed to show increases in serum bilirubin after injec- 

 tion of heniatin. Duesberg therefore supported the earlier views of 

 Bingold (265,267,269) that hematin was not an intermediate in the 

 breakdown. The metabolism of hematin is dealt with in the next 

 chapter. 



The last step, transformation of hematoporphyrin or of any other 

 porphyrin into bilirubin, has never been carried out directly in vitro, 

 while the clinical observations of Meyer-Betz (1931) showed only 

 that the injection of hematoporphyrin gave rise to a dangerous 

 photosensitization. 



This theory of the mechanism, therefore, while it still appears in 

 most modern textbooks and reviews, has extremely little to recom- 

 mend it from a biochemical point of view. In view of the ease with 

 which many tissues (cf. 22^0) are able to carry out the transformation 

 of hemoglobin to bile pigment, the exact mechanism was envisaged 

 rather vaguely as an enzymic process. 



1.3. Importance of Biliverdin 



The earliest observers of bile pigment formation noted the appear- 

 ance of biliverdin together with bilirubin. In 1870, Langhans pub- 

 lished his classical description of the hemoglobin breakdown in 

 hematomas. He found biliverdin in phagocytic cells entering the 

 outer zone of the blood extravasation, while hematoidin crystals 

 appeared further inside in the blood clot. Lignac (174.3) later con- 

 firmed these observations and concluded that bilirubin had diffused 

 into the inner necrotic zone. Rich (2238) found biliverdin in phago- 

 cytic wandering cells ingesting red corpuscles in tissue cultures, and 

 Stein (2618), in cultures of chicken embryo liver incubated with 

 hemolyzed blood. In the classic experiments of Minkowsky and 

 Naunyn (1959) much biliverdin was seen in the phagocytic Kupffer 

 cells of geese after arsine poisoning; this was confirmed by McNee 

 (1842) and Lepehne (1717) who also observed biliverdin in the 

 Kupffer cells of normal pigeons and geese. Auld (98) found it in the 

 endothelial cells of the rabbit spleen after phenylhydrazine adminis- 

 tration. 



In view of these observations and the obvious appearance of the 

 blue-green stage in a bruise before the yellow stage, it seems aston- 

 ishing that most workers relegated biliverdin to the status of a sec- 

 ondary oxidation product of bilirubin. An exception was MacMunn 



