Superoxide Generating Activity of Nicotinamide Coenzymes

It has been shown that nicotinamide coenzymes (NADPH, NADH, NADP⁺, and NAD⁺) are capable of generating superoxide anions (\({\text{O}}_{2}^{{ - \,\bullet }}\)) in an alkaline environment. The superoxide-generating activity of the coenzymes is associated with high pH values and is sensitive to SOD. However, nicotinamide itself, being a functional part of coenzyme molecules, does not have this property. Polarographic studies showed that in the presence of coenzymes, molecular oxygen is consumed from the buffer, namely oxygen activation occurs due to the formation of \({\text{O}}_{2}^{{ - \,\bullet }}\). Based on the obtained results and in accordance with the literature, our observations suggest that the formation of adducts of nicotinamide, which is part of the coenzyme molecule, and hydroxyl anions (OH^–) may lead to the formation of \({\text{O}}_{2}^{{ - \,\bullet }}\). Under mild conditions in the organism, the studied coenzymes, while performing their main functions, are expected to generate superoxide, meaning that they can be signaling molecules.