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Antioxidants

Antioxidants

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Antioxidants

Antioxidants are molecules that slow or prevent the oxidation of other chemicals. Oxidation is a redox chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can involve the production of free radicals, which can form dangerous chain reactions. Antioxidants can terminate these chain reactions by removing radical intermediates and can inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols or phenols.

Although oxidation reactions are critical for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Low levels of antioxidant molecules or inhibition of these antioxidant enzymes causes oxidative stress and may damage or kill cells.

As oxidative stress has been implicated in the pathogenesis of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of such diseases. Antioxidants are also widely used as ingredients in dietary supplements in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease. Although some studies have suggested antioxidant supplements have health benefits, other large clinical trials did not detect any benefit for the formulations tested, and excess supplementation may occasionally be harmful. In addition to these uses in medicine, antioxidants have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.

A paradox in metabolism is that while the vast majority of complex life requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species. Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.

The reactive oxygen species produced in cells include hydrogen peroxide (H2O2), hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (-OH) and the superoxide anion (O2-). The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton reaction. These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins. Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms, while damage to proteins causes enzyme inhibition, denaturation and protein degradation.

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species. In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain. Particularly important is the reduction of coenzyme Q in complex III, since a highly reactive free radical is formed as an intermediate (Q.-). This unstable intermediate can lead to electron leakage when electrons jump directly to molecular oxygen and form the superoxide anion, instead of moving through the series of well-controlled reactions of the electron transport chain. In a similar set of reactions in plants, reactive oxygen species are also produced during photosynthesis under conditions of high light intensity. This effect is partly offset by the involvement of carotenoids in photoinhibition, which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres and thereby preventing superoxide production.

Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). In general, water-soluble antioxidants react with oxidants in the cell cytoplasm and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation. These compounds may be synthesized in the body or obtained from the diet. The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid are more evenly distributed throughout the body.

The relative importance and interactions between these different antioxidants is a complex area, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another. The action of one antioxidant may depend on the proper function of other members of the antioxidant system. The amount of protection provided by any one antioxidant therefore depends on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.

Some compounds contribute to antioxidant defense by chelating metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin. Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes.


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