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Reduction of cytochrome c from both horse heart and Candida krusei by FeSO4 has been demonstrated. This reaction was stimulated by nalidixic acid and structurally related compounds, and the effect was more pronounced for the yeast cytochrome. Divalent metal ions other than Fe2+ lessened or abolished the stimulation by these compounds. Fe2+ and other metal ions altered the spectra of nalidixic acid and related compounds indicating the formation of metal chelate complexes. 1,10-Phenanthroline inhibited reduction of cytochrome c by Fe2+. Other divalent metal ions relieved the inhibition, probably by forming chelates with 1, 10-phenanthroline. These results suggest that metal ion chelation may be involved in the molecular mode of action of nalidixic acid and related drugs. The relevance of this artificial election transfer system to bacterial electron transfer in vivo is discussed.
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