Superoxide dismutase Sample Clauses

Superoxide dismutase. Superoxide radical spontaneously dismutes to O2 and hydrogen peroxide (H2O2) quite rapidly. However 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). At the subnanomolar concentrations superoxide can inactivate the citric acid cycle enzyme aconitase, can poison energy metabolism and releases potentially toxic iron. Aconitase is one of several iron-sulfur containing dehydratases in metabolic pathways shown to be inactivated by superoxide (Xxxxxxx et al., 1995). Therefore SOD is required to actively remove superoxide quickly at all concentrations. To this end SOD has one of the largest reaction rate with its substrate of any known enzyme, this reaction being only limited by the frequency of collision between itself and superoxide. Hence the SOD catalysed dismutation is favoured when concentrations of superoxide radicals are low, which occurs under physiological conditions, (Figure 1.3) and even more favoured as concentrations of superoxide become higher. There are currently three identified members of the enzyme family, namely cytosolic Cu/Zn SOD (SOD1), mitochondrial Mn-SOD (SOD2) and extracellular SOD or ec-SOD (SOD3) (Xxxxxx and Xxxxxx, 2004). The isoforms differ in their location, Cu/Zn SOD is found in the cytosol, Mn-SOD is localised to the mitochondria and ecSOD is found in the extracellular space. Cu/Zn SOD is the most widely distributed of these enzymes and comprises approximately 90% of the total SOD pool. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amidst massive oxidative stress (Xx et al., 1995). Mice lacking SOD1 develop a wide range of pathologies, including hepatocellular carcinoma (Xxxxxxx et al., 2005), an acceleration of age-related muscle mass loss (Xxxxxx et al., 2006), an earlier incidence of cataracts and a reduced lifespan. Mice lacking SOD3 do not show any obvious defects and exhibit a normal lifespan, though they are more sensitive to hyperoxic injury (Xxxxxxx et al., 2006).