396 VIII. HEMATIN ENZYMES, I. CYTOCHROME SYSTEM 



hematin also undergoes oxidation with liberation of its iron (1668). 

 The alteration of the globin part by the acid alters the oxygen-heme 

 linkage in such a way that the oxygen becomes activated and an 

 intramolecular oxidation of the globin ensues. If ascorbic acid is 

 present, it is oxidized instead of the globin. The oxidation occurs 

 instantaneously on acidification {1686); if ascorbic acid is added 

 shortly after acidification, much less of it is oxidized. The activated 

 oxygen reacts directly with ascorbic acid in an oxyhemoglobin- 

 ascorbic acid complex and the globin is thus protected. 



Other substances such as bilirubin {690) and biliverdin {1686, 

 1712) are oxidized in a more complicated way by the system. Here 

 there is no immediate decay of the active system after acidification. 

 The reaction of the activated oxygen with the globin leads to forma- 

 tion of hydrogen peroxide, which oxidizes these substances, the "acid 

 hematin" acting as peroxidase. These experiments reveal once more 

 the importance of hydrogen donor groups in the protein molecule. 



The activation of oxygen is not restricted to the effects of 

 acidification. Oxygen acting on dried oxyhemoglobin causes not only 

 formation of hemiglobin but also oxidative denaturation of the globin 

 {1293). If oxyhemoglobin is denatured by pyridine, again only 50% 

 of its oxygen is liberated instead of the 75% theoretically expected. 

 The reaction between cupric ions and oxyhemoglobin has been studied 

 by Rawlinson {2218). The oxidation of the iron of oxyhemoglobin 

 is accompanied by an oxidative denaturation of the globin by acti- 

 vated oxygen. There is also a direct denaturation of the globin if 

 hemoglobin or hemiglobin react with cupric ions, but this requires a 

 greater excess of copper than the denaturation of oxyhemoglobin. 

 In contradistinction to ferricyanide, bivalent copper thus causes the 

 formation of active oxygen, and intramolecular oxidation of the globin 

 by it. It is still unexplained why the oxygen liberated from oxyhemo- 

 globin by ferricyanide is unable to react with the hydrogen donor 

 groups of the globin, at least under certain conditions, whereas it is 

 able to react with added hydrogen donors such as ascorbic acid {2873) 

 or cysteine {291^0). 



Whatever may be the explanation of the mode of action of the 

 activated oxygen, it has been demonstrated that the inactive trans- 

 port oxygen of oxyhemoglobin is readily converted into activated 

 oxygen, and that this is able to react with hydrogen donor groups in 

 the protein part of the molecule. 



