Antioxidants are intimately involved in the prevention of cellular damage that is the common pathway for cancer, aging, and a variety of diseases.
Reactive oxygen species (ROS), by-products of cellular respiration, protein folding, and end products of a number of metabolic reactions, include the superoxide anion (O2¯), hydrogen peroxide (H2O2), and the hydroxyl radical (OH*). ROS are intracellular chemical species that are formed upon partial reduction of oxygen (O2). As their name suggests, ROS are more chemically reactive than O2; thus, historically, ROS were thought to function exclusively as cellular damaging agents, indiscriminately reacting towards lipids, proteins, and DNA. However, over the past two decades, there is growing appreciation for the role of ROS as mediators of intracellular signaling to regulate numerous physiological and biological responses (i.e. redox biology).
Different types of ROS have different intrinsic chemical properties, which dictate their reactivity and preferred biological targets. The two main sources of ROS are mitochondria and the family of NADPH oxidases (NOXs). Complex I, II and III within the mitochondrial electron transport chain generate superoxide by the one-electron reduction of molecular oxygen. Complex I, II, and III release superoxide into the mitochondrial matrix where superoxide dismutase 2 (SOD2) rapidly converts it into H2O2. Complex III can also release superoxide into the mitochondrial intermembrane space. Specific SOD enzymes can localize in the cytosol (SOD1) and the extracellular matrix (SOD3) and convert superoxide to H2O2 at a rate that is diffusion-limited. H2O2, the more stable and diffusible form of ROS, is selectively reactive towards cysteine residues on proteins and therefore can control cell signaling. Peroxiredoxins (PRXs) have emerged as critical regulatory systems that quench H2O2. Glutathione peroxidases (GPXs) can also convert H2O2 to water in the cytosol and mitochondria. GSH can get reduced and therefore re-activated by glutathione reductase and NADPH. Lastly catalase is found in peroxisomes and removes intracellular H2O2 without cofactors.