OXIDATIVE MECHANISMS IN ANIMAL TISSUES 29 



dase by the cytochromes. Now Barron (8) has presented ample 

 evidence that cyanide hemochromogens are able to act as reversible 

 oxidation-reduction catalysts. If the iron in such cyanide complexes 

 can be reduced, why is the ferric iron of the cyanide complex of 

 cytochrome oxidase not reduced? 



As one answer to this question I suggested several years ago (3) 

 that the oxidation-reduction potential of the cytochrome oxidase 

 system is lowered in the presence of cyanide below that of cyto- 

 chrome a or c. The reduction of cytochrome oxidase by these com- 

 pounds could then not occur and the respiratory chain as a whole 

 might thus be blocked. The experiments of Barron (8), which showed 

 that the cyanide hemochromogen systems were the most negative 

 of the hemochromogen systems investigated, were cited in support 

 of this idea. Since then Clark and his associates (10) have presented 

 their thorough analysis of such hemochromogen systems. As a result 

 of this study it may be said that the potentials of iron porphyrin 

 systems vary according to the type of nitrogen compound associated 

 with them. Also, if the aflBnity of the nitrogenous compound is great- 

 est for the ferric form, the potential of the system will decrease 

 progressively as the concentration of the coordinating compound is 

 increased. The reverse holds true if the feiTous form displays the 

 greatest affinity. Now assuming that the cytochrome oxidase system 

 behaves in a similar manner, we may picture the effect of cyanide 

 on the potential of the cytochrome oxidase system as shown in 

 Figure 4. Here the cytochrome oxidase system is arbitrarily assigned 

 a potential of 0.5 volts at pH 7.0. The potential of this system is 

 plotted against the log of the concentration of the coordinating com- 

 pound, as is done by Clark et al. (10) for the hemochromogen 

 systems. It is assumed that only the ferric form of cytochrome 

 oxidase reacts with cyanide and that since the first noticeable effects 

 of cyanide poisoning result at concentrations of 10~^ to lO*' molar, it 

 is within this range that a potential shift will first occur.* The 

 potential is assumed to change according to a 0.12 slope, since this 

 value has been found to hold for certain hemochromogen sys- 

 tems (10). It will be seen that, according to such a scheme, when the 

 concentration of cyanide reaches 10'^ molar, the potential of the 



* As shown by Clark et al. (10) for hemochromogen systems, this point de- 

 pends also upon tlie concentration of the hemochromogen system. The con- 

 centration of the cytochrome oxidase system is of course not known. It is 

 probably of the order of magnitude of the systems studied by Clark et al. (10) 

 if tlie concentration of cytochrome c in the tissues can be used as an index. 



