RADICAL CHAIN THEORY 387 



In these chains a large number of substrate molecules are transformed, 

 in our case hydrogen donors of an oxidase. Finally the ferrous 

 desoxyenzyme is retransformed to the ferric enzyme by a chain- 

 breaking reaction, such as: 



/ 

 (Fe'+) + OH -> (Fe'^) + OH" 



or the latter is re-formed by autoxidation of the former. In a similar 

 way the actions of catalase and peroxidase were explained (c/. 

 Chapter IX). 



The first idea, i.e., that of monovalent dehydrogenation, is now 

 well proved for the reaction of cytochromes with their substrates. 

 We now know that the flavoproteins which react with cytochrome c 

 (as well as the pyridine coenzymes which react with the flavoproteins) 

 are able to form radicals which are stabilized by resonance {cj. 

 Michaelis, 1935,2516; Pauling and Wheland, 2128,30Jf2). It is almost 

 certain that all the reactions of the hematin enzymes are such mono- 

 valent reactions. 



The second proposition, that of oxidation of the substrate by 

 radical chains, however, is certainly not correct for the cytochrome 



> 

 system. The substrate radical HA {e.g., dehydrogenated flavopro- 

 tein) is stabilized by resonance and is unable to initiate radical chains 

 of the kind postulated by Haber and Willstiitter. In Chapter IX it 

 will be shown that even with catalase and peroxidase, where such 

 radical chains are more likely, the radical chain theory has been 

 subjected to a well-founded criticism on kinetic, thermodynamic, and 

 specificity grounds (250,709,1099). Some of these objections have 

 been met by Weiss by adjustments of the theory, for instance by the 

 assumption of short radical chains. 



There are, however, even more fundamental biological reasons 

 against the radical chain theory as the explanation of the function 

 of respiratory enzymes. It appears impossible to bring into harmony 

 with the formation of highly diffusible, indiscriminately reacting free 

 radicals the remarkable correlation between the various enzymes, 

 which has been demonstrated lately in numerous instances. In this 

 connection it is significant that Haber and Willstiitter had to assume 

 a rather improbable trimolecular reaction between a radical, hydrogen 

 donor, and hydrogen peroxide in order to account for the fact that 

 peroxidase has no catalatic activity (cf. Chapter IX). 



