MODE OF ACTION OF RESPIRATORY ENZYME 397 



6.4. Mode of Action of the Respiratory Enzyme 



When we attempt to apply the experiences gained with the 

 autoxidation of hemoglobin to the main unsolved problem of the mode 

 of action of the respiratory enzyme, the transformation of the form 

 Fe^"'"02 to Fe^"*", we are quite conscious of entering the realm of 

 speculation. Clark stated in 1939 (450): "It is not unlikely that the 

 activation of oxygen ... is within a co-ordination complex and by 

 a specific channel that removes the action from the general field." 



Cytochrome oxidase and cytochrome c form such a complex, in 

 which at least two molecules of hematin iron are present (cf. Section 

 3.6.4.). We assume that, as in the autoxidation of hemoglobin, a 

 hydrogen donor group H2X is present in the protein of the oxidase 

 or bound to it, and plays a role in the autoxidation of both ferrous 

 heme iron atoms in the complex of cytochrome oxidase (Fe„^) with 

 cytochrome c (Fe^j^,) : 



Fet (H2X) FeS + O2 ^ Felt (X) + FeJ + 2 OH" 



It is possible that the second, component of cytochrome oxidase, 

 recently isolated by Haas {1075) contains the hydrogen donor group 

 H2X. Figure 5 shows the assumed catalytic cycle. In this scheme 



Fe XH2 



I L_ 



represents the oxidase, and 



Fe 



represents cytochrome c, the cross in the latter indicating the point 

 at which the hydrogen donor, HA {e.g., cytochrome reductase) is 

 attached to cytochrome c. 



The oxidase is written on the left side, cytochrome c on the right 

 side, both forming the complex; whether this complex dissociates 

 at certain stages of the cycle or not is of no significance for the 

 scheme. Step 1 in Figure 5 represents the autoxidation as discussed 

 above. Ferricytochrome c is then reduced by the substrate in steps 

 2 and 3. Step 4 represents the oxidation of ferrocytochrome c by 

 the ferric oxidase. This is the slowest rate-determining reaction 

 (Warburg, 2929) and is inhibited by cyanide, the cyanide combining 

 with the ferric oxidase. The ferrous oxidase now combines with 

 oxygen (step 5). This reaction is inhibited by carbon monoxide. In 



