REDUCTION OF BILIVERDIX TO BILIRUBIN 545 



The amounts of daily excretion of bilirubin in man and dog have 

 been discussed in Section 2.2.1. 



8.2. Reduction of Biliverdin to Bilirubin 



In a preliminary note Barry and Levine (190) mention the reduc- 

 tion of biliverdin to bilirubin by liver enzymes and the increase of 

 this reduction by glucose. We have been unable, however, to find 

 the publication of the evidence. In 1936 the subject was studied by 

 Lemberg and Wyndham (1715). If biliverdin solutions are incubated 

 with liver slices, typical "hematoidin" crystals appear in the liver 

 cells. The reducing power of the liver of starved animals was smaller 

 than that of normal animals; in the frog, which excretes biliverdin 

 in its bile, the reducing power of the liver was small. Anaerobically 

 all tissues were able to reduce biliverdin; aerobically, liver, kidney, 

 brain, spleen, and skin, and particularly the hair sheath, but not 

 lung, muscle, or heart. All tissues except heart prevented the oxida- 

 tion of bilirubin by atmospheric oxygen. The observation of Sumner 

 and Nyman {27OJ4) that milk peroxidase catalyzes the oxidation of 

 bilirubin to biliverdin is therefore unlikely to be of physiological 

 interest. Several enzyme systems were shown to use biliverdin as 

 hydrogen acceptor in vitro, particularly lactic acid dehydrogenase 

 and systems acting with glucose as substrate; ascorbic acid reduced 

 biliverdin more slowly than these enzyme systems. 



Biliverdin added to blood was not reduced, but since enzyme 

 systems reacting with biliverdin occur in the intact erythrocyte, 

 they reduce intracorpuscular biliverdin to bilirubin. The small 

 amounts of biliverdin obtainable from normal erythrocytes are 

 derived from choleglobin or a verdohemochrome, while phenyl- 

 hydrazine exhausts the reducing sj'stems and biliverdin is therefore 

 no longer reduced. 



The reduction of biliverdin to bilirubin by liver enzymes has been 

 confirmed by Baumgartel (194)', the reductases of intestinal bacteria 

 which reduce bilirubin to urobilinogen are unable to reduce the central 

 CH group of biliverdin and to form bilirubin. Biliverdin is therefore 

 not transformed into urobilinogen in the intestine. These observa- 

 tions explain why in animals in which biliverdin is normally found, 

 e.g., in frog bile (2055), in Rhodnius (3081), or under pathological 

 conditions in human bile (11^62), glucose causes the formation of 

 bilirubin, and, on the other hand, why the excretion of biliverdin in 

 the bile is observed under conditions of starvation (1342) or necrosis 



