46 A SYMPOSIUM ON RESPIRATORY ENZYMES 



of hydrogen transport may exist. Dr. Stotz has agreed to open the 

 discussion of this interesting possibiHty. 



POSSIBILITY OF A BY-PASS AROUND THE 



CYTOCHROME SYSTEM 



ELMER STOTZ 

 Harvard University 



The possibihty of a 'Tsy-pass" around the cytochrome system in 

 certain phases of tissue respiration has eUcited considerable discus- 

 sion of late. The discovery of the flavoproteins, and their function 

 in isolated systems as autoxidizable substances, had raised a doubt 

 as to the exclusive role of the iron system in "oxygen activation." 

 However, this threat to the autonomy of the iron compounds was 

 dispelled by the correction of certain technical points and by the 

 work of Theorell and of Barron. The most recent threats have come 

 from a study of the effects of cyanide and azide ( as oxidase inhibit- 

 ors) on the respiration of "resting" and "stimulated" tissues. The work 

 of Stannard and of Korr on this topic is reviewed in my paper on 

 page 169. Their results may be summarized briefly by the state- 

 ment that the respiration of "resting" tissue is insensitive to azide, 

 whereas that of the stimulated tissue becomes azide-sensitive. Tissues 

 in either phase may, however, be cyanide-sensitive. The 'Iby-pass" 

 theory therefore implies that in the resting tissue an oxidation path- 

 way other than the cytochrome system is functioning. In Korr's 

 terminology, tissues that have been stimulated may liberate sub- 

 stances that "link" or "gear" the reducing systems to the cytochrome 

 system. 



The by-pass theory, although possibly correct, is in my judgment 

 a rather sweeping conclusion to make from evidence based chiefly 

 on the use of these inhibitors, and without knowledge of the nature 

 of an alternative pathway. Even if we assume an identical action 

 of the inhibitors in isolated systems, as in the muscle and tissue 

 slices, we are far from understanding the mechanism of their action. 

 Stannard believes that cyanide affects not only cytochrome oxidase 

 but also other enzymes essential in respiration, and, to be sure, he 

 offers some evidence for this belief. On the other hand, this does 

 not imply that azide is any more specific than cyanide and that only 

 the effects of the former need be considered. 



It would seem more conservative at the moment to consider how 

 the differences between cyanide and azide might be explained on 

 the basis of the existing knowledge of the cytochrome-cytochrome 



