OXIDATIVE MECHANISMS IN ANIMAL TISSUES 



17 



school, headed by Wieland, claimed that activation of the substrate 

 was most important. In particular, activation of the hydrogen of the 

 substrate was stressed. Such activated hydrogen was believed 

 capable of reacting with atmospheric oxygen to form water. Both 

 schools seemed to agree that direct reaction between molecular 

 oxygen and the substrate could occur. A release of energy in one 

 tremendous burst was thus implied. As more data became available 

 it became evident that both schools of thought were right and that 

 biological oxidations took place only after both oxygen and the food- 

 stuff to be burned were acted upon by intracellular enzymes. Within 

 the last ten years we have also learned that it is doubtful whether 

 any direct reaction occurs between oxygen and the substrate to be 

 burned. Interposed between oxygen and the substrate are a series 

 of so-called carriers through which electron exchange occurs, and 

 energy is released in a series of successive steps. 



Beginning with the oxygen end, let us examine the chain of 

 events more closely. Evidence for the activation of oxygen has de- 

 pended largely upon the use of so-called respiratory poisons. As a 

 result of Warburg's earlier belief that iron in some form or other 

 was the activator of oxygen, cyanide and carbon monoxide have 

 become classical tools for the study of respiratory mechanisms. 

 With the aid of these tools it has been proved, thanks to the labora- 

 tories of Warburg and Keilin, that at least four iron porphyrin com- 

 pounds participate in biological oxidations. One of these, now 

 commonly called cytochrome oxidase, is known largely as the result 

 of its shadow-boxing with carbon monoxide. The other three, known 



CO dark . Fe^^CO - Cytochronne Oxidase 



+ re**Cytochrome Oxidase 



-» Fe ^O, ■ Cytochrome Oxidase 



■H* 



Fe^^^CN-Cytochrome Oxidose , ' CN' t Fe***Cytochrome Oxidase + H^O 



Fe*t!^^^^ Fe*t* Fe^t^. Fe^*-^ 



Cylochrome Oxidase~---,^Cy+ochrome 1 g ^\^tochrome | c ^\^ytochrome b 

 Fe** ^"~~^ Fe** ^^ Fe** ^^ Fe** 



Figure 1. — The cytochrome system 



