Superoxide Dismutase and Catalase

More than two billion years ago, photosynthesis of cyanobacteria (blue-green algae) created an environment in the Earth’s atmosphere that gave rise to oxygen. This biologically critical gas now constitutes about 21% of the Earth׳s atmosphere and plays a crucial role in energy production in nearly all aerobic organisms. The use of molecular oxygen produces an array of reactive products collectively known as “reactive oxygen species” (ROS), which have pro-survival or pro-death consequences depending on the local cellular environments. Two species, superoxide anion (O2•−) and hydrogen peroxide (H2O2), are key signaling molecules at physiological levels. However, excessive levels of these ROS can damage biomolecules, including nucleic acids, proteins, and lipids. To regulate the physiological levels of ROS, organisms use a variety of antioxidant enzymes working in concert with copious low-molecular-weight antioxidants. Here, we focus on enzymes that remove O2•− and H2O2, specifically superoxide dismutase and catalase, respectively. Significant advances have been made in understanding the role and regulation of these enzymes under physiological, oxidative stress, and disease conditions involving neurological and metabolic regulation, modulation by environmental factors, aging, and cancer. This understanding, coupled with recognition of the different redox stresses of normal and cancer cells, has set the stage for developing a redox-active antioxidant (RAA) approach to cancer therapy. Small molecule RAAs mimicking these enzymes have been produced and are being tested in clinical trials with encouraging results. Thus, we may expect that identification of RAA targets and translation of this concept will continue into the future.