Influence of metallic chelates on the diphosphopyridine nucleotide oxidase and diphosphopyridine nucleotide-cytochrome c reductase systems.

The need for additional study on the specific relation between metallic ions and metabolic function, especially in the case of the diphosphopyridine nucleotide oxidase system, has been expressed by Mahler (1) and others. This is particularly indicated in view of the fact that a number of the known components of this system contain iron. While it is broadly concluded that iron compounds facilitate electron transfer from the reduced flavins to the various cytochromes, the exact nature of this effect is not understood. It seems unlikely that free ferrous ions transfer electrons to cytochrome c since the oxidation-reduction potential of the Fe++:Fe+++ system is much more positive than that of cytochrome c. Metallic complexes, however, could mediate electron transport because of their more negative potential. According to another explanation of these reactions, metallic ions might act by effecting a tighter molecular bonding between the reactants. Indeed, Green (2) has suggested that metal atoms may connect neighboring hemes and crosslink parallel molecular chains. These considerations, therefore, rendered the analysis of the effects produced by the addition of metallic organic complexes to the DPNH-oxidase system of considerable interest. Preliminary investigations in which a spectrum of 10 naturally occurring and synthetic organic compounds containing iron in the ferrous and ferric states was tested revealed the ability of the ferric salt of ethylenediaminetetraacetic acid (Fe(III)-EDTA) to accelerate the DPNH-oxidase system to a marked degree. More detailed studies of this effect and the nature of the reaction involved constitute the subject of this investigation.