Superoxide Dismutase - Biochemistry

Biochemistry

Simply stated, SOD out-competes damaging reactions of superoxide, thus protecting the cell from superoxide toxicity. The reaction of superoxide with non-radicals is spin forbidden. In biological systems, this means its main reactions are with itself (dismutation) or with another biological radical such as nitric oxide (NO) or with a transition-series metal. The superoxide anion radical (O₂−) spontaneously dismutes to O₂ and hydrogen peroxide (H₂O₂) quite rapidly (~105 M−1s−1 at pH 7). SOD is necessary because superoxide reacts with sensitive and critical cellular targets. For example, it reacts the NO radical, and makes toxic peroxynitrite. The dismutation rate is second order with respect to initial superoxide concentration. Thus, the half-life of superoxide, although very short at high concentrations (e.g., 0.05 seconds at 0.1mM) is actually quite long at low concentrations (e.g., 14 hours at 0.1 nM). In contrast, the reaction of superoxide with SOD is first order with respect to superoxide concentration. Moreover, superoxide dismutase has the largest k_cat/K_M (an approximation of catalytic efficiency) of any known enzyme (~7 x 109 M−1s−1), this reaction being only limited by the frequency of collision between itself and superoxide. That is, the reaction rate is "diffusion limited". Even at the subnanomolar concentrations achieved by the high concentrations of SOD within cells, superoxide inactivates the citric acid cycle enzyme aconitase, can poison energy metabolism, and releases potentially toxic iron. Aconitase is one of several iron-sulfur containing (de)hydratases in metabolic pathways shown to be inactivated by superoxide.