What are free radicals?DefinitionFree radicals are molecules or atoms with unpaired electrons. This open shell configuration is highly reactive, making the molecule or atom extremely likely to take part in a chemical reaction. Generally, radicals can be formed by homolytic bond cleavage usually between 2 atoms of similar electronegativity (often O-O or O-N bonds), or by single electron oxidation or reduction of an atom or molecule (eg, production of superoxide anions). Molecular oxygen is an example of a stable radical. Vitamin E forms a relatively stable (resonance stabilization) free radical intermediate during the repair of free radical damage. Persistent radicals are also relatively stable due to steric hindrance near the radical center, making it more difficult for the radical to react with another molecule. Examples of peristent radicals are nitroxides. Stable radicals and persistent radicals are examples of long lived radicals.
Biology of free radicalsGenerally, free radicals react with other molecules, damaging them. However some processes such as the killing of bacteria by neutrophil granulocytes is beneficial. The most important oxygen-based free radicals are superoxide and the hydroxyl radical, produced from the reduction of molecular oxygen. These free radicals are extremely reactive and are often associated with cell damage, mutations, and even malignancies. Symptoms of aging such as atherosclerosis is thought to be due to oxidation by free radicals. The free radical theory of aging postulates that free radical damage is the primary mechanism of aging. Free radicals are also associated with liver damage due to alcohol and the development of emphysema from ciagrette smoking. The body has developed a number of mechanisms to minimize free radical damage and even repair damage. Enzymes such as superoxide dismutase, catalase, [[glutathione peroxidase]], and glutathione reductase, as well as antioxidants such as vitamin A, vitamin C, vitamin E, and polyphenols play important roles in protecting the body from free radical damage.
Mitochondria and free radicalsFree radicals can be produced inside mitochondria and are frequently released into the cytosol. The production of ATP in the mitochondria involves the transport of protons across the inner mitochondrial membrane via the electron transport chain. The electron transport chain passes electrons among molecules with each successive molecule having a greater reduction potential. The final electron acceptor is an oxygen molecule that normally is reduced to water, but in a small but significant percent of cases (1-2%), a superoxide anion results. The superoxide anion will take an extra electron from mtDNA, the mitochondrial membrane, proteins, resulting in mitochondrial damage. If too much damage takes place, the cell will undergo apoptosis. Apoptosis occurs due to a cascade initiated by Bcl-2 proteins on the surface of mitochondria. The free radical theory of aging states that aging occurs due to a loss of energy producing cells when mitochondria begin to die due to free radical damage.
Free radical defenseSuperoxide dismutase (SOD) is present in both the mitochondria and the cytosol. SOD reacts with 2 superoxide anions to form 1 molecule of hydrogen peroxide. Hydrogen peroxide can be easily transformed into the dangerous hydroxyl radical via reaction with Fe2+. Catalase reacts with hydrogen peroxide to form water and oxygen. Glutathione peroxidase can also react with hydrogen peroxide, by reducing hydrogen peroxide and oxidizing glutathione. Glutathione is an antioxidant. Antioxidants are an important part of the free radical defense mechanism along with the enzymatic processes.
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