506 XI. HEMOGLOBIN CATABOLISM, I 



{183 Jf), who in 1885 assumed a direct transformation of hemoglobin 

 into biliverdin. This failure to interpret observed facts correctly — 

 an interesting example is the paper of Auld {98) — is due to historical 

 facts. While bilirubin had been obtained in a pure crystalline state, 

 biliverdin was then known only as the green stage of the Gmelin 

 reaction and as a product of the autoxidation of bilirubin, for instance, 

 in bile standing exposed to the air. The analysis of the very impure 

 products then available indicated a higher oxygen content for bili- 

 verdin than for bilirubin. This was rectified when Lemberg {1676) 

 succeeded in crystallizing biliverdin; the proof that it differed by 

 only two hydrogen atoms from bilirubin made it possible to explain 

 most of the earlier physiological observations on the basis of the 

 hypothesis that bilirubin is formed in the body by a reduction of 

 biliverdin. This was finally proven by Lemberg and Wyndham 

 {1715), when they investigated the actual reducing systems respon- 

 sible for the reduction {cf. Section 8.). 



Biliverdin formation in animal tissues had actually been observed 

 very early. In 1830, Breschet {335) gave an account of the green 

 pigment of the dog's placenta. Toward the end of the last century 

 this was studied by a number of outstanding histologists (5i^,6^|, 

 1229,1739,2682,2730). The green pigment (and also bilirubin) has 

 occasionally been found in the placenta of other species {1875). Its 

 close relationship to biliverdin was suspected for some time but its 

 identity with the latter was not finally proved until the investiga- 

 tions of Lemberg and Barcroft {1691) in 1932. 



In 1858 Wicke {3068) described a green-blue pigment in bird egg 

 shells, which Sorby {2595) named oocyan. Its chemical structure 

 remained uncertain {8If8,1587,167Jf,17Jt.0,2802) until Lemberg {1676, 

 1680) finally confirmed its identity with biliverdin. 



Fresh human or ox bile is usually yellow and contains only bili- 

 rubin; the bile of some other species contains only biliverdin, e.g., 

 that of amphibia {1681,2055,2399) and of birds {23 W. Nisimaru 

 {2055) found excretion of green-blue bile when the liver of the giant 

 frog was perfused through the hepatic artery with solutions of horse 

 hemoglobin. The claim of von Recklinghausen {2221) that biliverdin 

 is formed in sterile frog blood has not been confirmed {224-0). 



In frogs' blood serum, biliverdin was observed in 1850 by Kunde 

 {1623) after liver extirpation. McNee {18^2) found it in the serum of 

 hepatectomized geese. While it does not occur in normal human sera, 

 Moleschott {1970) found it in pathological serum in 1852. Biliverdin 



