Epinephrine and other activators of prostaglandin endoperoxide synthetase can reduce Fe³⁺-heme to Fe²⁺-heme

In view of recent evidence that activation of prostaglandin endoperoxide synthetase by lipid peroxides may relate to the ability of such peroxides to reduce heme, we tested other activators of this enzyme. Epinephrine, norepinephrine, ascorbic acid and tryptophan were all found to reduce Fe³⁺-heme to Fe²⁺-heme, though trypophan was considerably weaker than the others. We suggest that reduction of heme by these compounds might account for their ability to reduce the lag phase on addition of substrate to the enzyme. Epinephrine was assessed for its effects on the lag phase in activation of soybean lipoxygenase and was found to cause a similar reduction of the lag phase of this related enzyme. These findings support the concept that reduction of Fe³⁺-heme to Fe²⁺-heme is critical to activation of both the prostaglandin endoperoxide synthetase and soybean lipoxygenase enzymes, and that mechanisms involved in regulation of the valence of iron are important for regulating enzyme activity.