Chemistry

A New SORt of Detoxification

Only six years after discovering the O₂•- detoxifying enzyme superoxide reductase (SOR), CNRS researcher Vincent Nivière and his team¹ in Grenoble have succeeded in suppressing production of H₂O₂, a toxic byproduct of the SOR reaction. Achieved by using the SOR enzyme coupled with the organometallic compound ferrocyanide, the finding could have a direct impact on a range of research concerned with the aging of the cell.

Free radicals are a waste product of chemical reactions. Lacking one electron, these elements become highly unstable and seek to recover the missing electron in any way possible, thus perturbing normal cellular chemical reactions. While natural defenses exist, they can be overwhelmed if there are too many of these radicals, ultimately leading to cell deterioration.

One of these free radicals, the superoxide radical O₂•-, is a toxic by-product of oxygen metabolism. Fortunately, cells possess O₂•- detoxifying enzymes. To date, two have been described: the superoxide dismutase (SOD), known for 35 years and present in almost all aerobic cells, and the more recently discovered superoxide reductase (SOR), which is only found in prokaryotic cells. But neither of these two systems is perfect. While eliminating the superoxide radical O₂•-, both produce H₂O₂, also a toxic substance and a precursor of HO• radicals, that in turn need to be eliminated from the cell by other enzymes. It would all be much simpler if the cell did not have to deal with H₂O₂. This is exactly the effect Nivière and his team managed to orchestrate, in collaboration with laboratories at the University of Orsay and the Commissariat à l'Energie Atomique (CEA Cadarache).² “SOR can bind with the organometallic compound ferrocyanide to form a reversible complex that reacts very efficiently with O₂•- radicals,” explains Nivière. “But H2O2, a toxic byproduct of the classical SOR reaction, is no longer produced.”

The researchers were surprised to discover that ferrocyanide–a well-known mediator in oxydo-reduction reactions–can be a cofactor of SOR. The unusual complex offers a new detoxification mechanism for the radical superoxide. This marks a meaningful step for studies on oxidative stress, which is a serious issue with implications not only for new antioxidant treatments concerning aging but also for diseases where a superoxide is involved, such as degenerative illnesses, Parkinson's and Alzheimer's diseases, and various forms of cancer.

Samantha Maguire