Reactive oxygen species are chemically reactive chemical species containing oxygen. Examples include peroxides, superoxide, hydroxyl radical, and singlet oxygen, in a biological context, ROS are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, during times of stress, ROS levels can increase dramatically. This may result in significant damage to cell structures, cumulatively, this is known as oxidative stress. ROS are also generated by sources such as ionizing radiation. Ionizing radiation can generate damaging intermediates through the interaction with water, since water comprises 55–60% of the human body, the probability of radiolysis is quite high under the presence of ionizing radiation. In the process, water loses an electron and becomes highly reactive, then through a three-step chain reaction, water is sequentially converted to hydroxyl radical, hydrogen peroxide, superoxide radical and ultimately oxygen. The hydroxyl radical is extremely reactive and immediately removes electrons from any molecule in its path, turning that molecule into a free radical, mitochondria convert energy for the cell into a usable form, adenosine triphosphate. The process in which ATP is produced, called oxidative phosphorylation, the last destination for an electron along this chain is an oxygen molecule. Superoxide is not particularly reactive by itself, but can inactivate specific enzymes or initiate lipid peroxidation in its protonated form, the pKa of hydroperoxyl is 4.8. Thus, at physiological pH, the majority will exist as superoxide anion, if too much damage is present in mitochondria, a cell undergoes apoptosis or programmed cell death. This cytochrome C binds to Apaf-1, or apoptotic protease activating factor-1, using energy from the ATPs in the mitochondrion, the Apaf-1 and cytochrome C bind together to form apoptosomes. The apoptosomes bind to and activate caspase-9, another free-floating protein, the caspase-9 then cleaves the proteins of the mitochondrial membrane, causing it to break down and start a chain reaction of protein denaturation and eventually phagocytosis of the cell. Superoxide dismutases are a class of enzymes catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in all cells exposed to oxygen. In mammals and most chordates, three forms of superoxide dismutase are present, sOD1 is located primarily in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first is a dimer, while the others are tetramers, sOD1 and SOD3 contain copper and zinc ions, while SOD2 has a manganese ion in its reactive centre. The genes are located on chromosomes 21,6, and 4, respectively
Image: Major cellular sources of Reactive Oxygen Species in living cells
Free Radical Mechanisms in Tissue Injury. Free radical toxicity induced by xenobiotics and the subsequent detoxification by cellular enzymes (termination).