Antioxidant mechanisms superoxide dismutases

Winn LM, Wells PG. Phenytoin-initiated DNA oxidation in murine embryo culture, and embryo protection by the antioxidative enzymes superoxide dismutase and catalase Evidence for reactive oxygen species-mediated DNA oxidation in the molecular mechanism of phenytoin teratogenicity. Mol Pharmacol 1995 48 112-20. 

Fig. 121.3 Antioxidant mechanism garlic inhibiting oxidative modification of LDL-C, scavenging ROS, enhancing the cellular antioxidant enzymes superoxide dismutase, catalase and glutothione peroxidase and glutothione in the cells, thus protecting endothelial cells from the injury by the oxidized molecules...

On the other hand, several ROS are highly cytotoxic. Consequently, eukaryotic cells have developed an elaborate arsenal of antioxidant mechanisms to neutrahze their deleterious effects (enzymes such as superoxide dismutases, catalases, glutathione peroxidases, thioredoxin inhibitors of free-radical chain reaction such as tocopherol, carotenoids, ascorbic acid chelating proteins such as lactoferrin and transferrin). It can be postulated that ROS may induce an oxidative stress leading to cell death when the level of intracellular ROS exceeds an undefined threshold. Indeed, numerous observations have shown that ROS are mediators of cell death, particularly apoptosis (Maziere et al., 2000 Girotti, 1998 Kinscherf et al., 1998 Suzuki et al., 1997 Buttke and Sanstrom, 1994 Albina et al., 1993). 

The enzyme copper, zinc superoxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) catalyzes the disproportionation of superoxide anion to dioxygen and hydrogen peroxide (equations 1 and 2). Crystallographic data can be found in References 41-46. This antioxidant enzyme is present in the cytosol and mitochondrial intermembrane space of eukaryotic cells and in the periplasmic space of bacterial cells as a homodimer of 32 kDa. Each monomer binds one copper and one zinc ion. The reaction mechanism involves the... 

ROS are maintained at tolerable levels through the combined efforts of antioxidant mechanisms, which include both enzymes and nonenzymatic molecules. Important antioxidant enzymes include superoxide dismutases (SODs), catalases (CATs), peroxidases, and those maintaining reduced glutathione (GSH) levels. Nonenzymatic antioxidants include GSH, a tripeptide containing a cysteinamino acid, and vitamins, such as vitamin A, E, and C. 

Little information about the mechanism of action of flavonoids is anticipated from in vivo studies. The mechanism of catechin and morin seems to be related to an increase of the activity of detoxifying enzymes like glutathione-S-transferase and NADPH quinone reductase [198, 211]. Similarly, EGCG effect at the colonic level is associated to an increase in tissue superoxide dismutase levels, suggesting that it may act through a potentiation of the antioxidative defense [210]. 

Superoxide dismutases (SOD EC 1.15.1.1) constitute a group of metalloisoenzymes that neutralise the very reactive superoxide radical, generated in the cell as a by-product of the reduction of molecular oxygen (Salin, 1988). SOD is a highly efficient enzyme system involved in the cellular antioxidant system (cf. section on defence mechanisms). 

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