Figure 1424

Cellular sources of reactive oxygen species (ROS) defense systems from free radicals. Superoxide and hydrogen peroxide are produced during normal cellular metabolism. ROS are constantly being produced by the normal cell during a number of physiologic reactions. Mitochondrial respiration is an important source of superoxide production under normal conditions and can be increased during ischemia-reflow or gentamycin-induced renal injury. A number of enzymes generate superoxide and hydrogen peroxide during their catalytic cycling. These include cycloxygenases and lipoxygenes that catalyze prostanoid and leukotriene synthesis. Some cells (such as leukocytes, endothelial cells, and vascular smooth muscle cells) have NADH/ or NADPH oxidase enzymes in the plasma membrane that are capable of generating superoxide. Xanthine oxidase, which converts hypoxathine to xanthine, has been implicated as an important source of ROS after ischemia-reperfu-sion injury. Cytochrome p450, which is bound to the membrane of the endoplasmic reticulum, can be increased by the presence of high concentrations of metabolites that are oxidized by this cytochrome or by injurious events that uncouple the activity of the p450. Finally, the oxidation of small molecules including free heme, thiols, hydroquinines, catecholamines, flavins, and tetrahydropterins, also contribute to intracellular superoxide production. (Adapted from [22]; with permission.)

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