Diphtheria toxin; a comparison between the diphtherial succinoxidase system and that of beef heart muscle.

The major iron-containing respiratory pigment of Corynebacterium diphtheriae is spectroscopically related to cytochrome b (l-3). In a previous communication (2) we presented evidence which suggests that diphtheria toxin may be closely related to the protein moiety of diphtherial eytochrome b. The tentative hypothesis was advanced that diphtheria toxin may act by interfering with the normal function of cytochrome b in the tissues of the susceptible host, possibly by blocking its synthesis. Before attempting to verify this hypothesis, it has seemed necessary to investigate further the r61e of cytochrome b both in mammalian tissue respiration and in the bacterial cell. There seems to be little doubt that cytochrome b is concerned in the oxidation of succinate by heart muscle succinoxidase preparations in which it may serve as a link between succindehydrogenase and the cytochrome c-cytochrome oxidase system (Keilin and Hartree (4) ; Ball et al. (5)). The diphtheria bacillus, on the other hand, contains very little cytochrome c or cytochrome oxidase, and cytochrome b appears to be the limiting factor concerned in succinate oxidation by these organisms (2). In the present study we have investigated the succinoxidase systems of beef heart muscle and of the diphtheria bacillus. The principal difference between the bacterial and mammalian systems resides in the relative amounts of the various components of the succinoxidase system present, as noted above. Of particular interest is the exceptionally high succindehydrogenase activity of the diphtheria bacillus, which parallels its high cytochrome b content. The evidence to be presented suggests that cytochrome b oxidation is the limiting factor in the oxidation of succinate by tissue and bacterial extracts in the presence of methylene blue and cyanide and that succindehydrogenase and cytochrome b may be identical both in diphtherial extracts and beef heart muscle succinoxidase preparations.