Model of the antioxidant
metaboliteglutathione. The yellow sphere is the
redox-active sulfur atom that provides antioxidant activity, while the red, blue, white, and dark grey spheres represent oxygen, nitrogen, hydrogen, and carbon atoms, respectively.
An
antioxidant is a
molecule that inhibits the
oxidation of other molecules. Oxidation is a
chemical reaction involving the loss of electrons or an increase in oxidation state. Oxidation reactions can produce
free radicals. In turn, these radicals can start
chain reactions. When the chain reaction occurs in a
cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often
reducing agents such as
thiols,
ascorbic acid, or
polyphenols.
[1]
Substituted
phenols and derivatives of
phenylenediamine are common antioxidants used to inhibit gum formation in gasoline (petrol).
Although oxidation reactions are crucial for life, they can also be damaging; plants and animals maintain complex systems of multiple types of antioxidants, such as
glutathione,
vitamin C,
vitamin A, and
vitamin E as well as
enzymes such as
catalase,
superoxide dismutase and various
peroxidases. Insufficient levels of antioxidants, or
inhibition of the antioxidant enzymes, cause
oxidative stress and may damage or kill cells. Oxidative stress is damage to cell structure and cell function by overly reactive oxygen-containing molecules and chronic excessive inflammation. Oxidative stress seems to play a significant role in many human diseases, including cancers. The use of antioxidants in
pharmacology is intensively studied, particularly as treatments for stroke and
neurodegenerative diseases. For these reasons, oxidative stress can be considered to be both the cause and the consequence of some diseases.
Antioxidants are widely used in
dietary supplements and have been investigated for the prevention of diseases such as cancer,
coronary heart disease and even
altitude sickness.
[2] Although initial studies suggested that antioxidant supplements might promote health, later large
clinical trials of antioxidant supplements including beta-carotene, vitamin A, and vitamin E singly or in different combinations suggest that supplementation has no effect on mortality or possibly increases it.
[3][4][5]Randomized clinical trials of antioxidants including beta carotene, vitamin E, vitamin C and selenium have shown no effect on cancer risk or increased cancer risk associated with supplementation.
[6][7][8][9][10][11][12] Supplementation with selenium or vitamin E does not reduce the risk of cardiovascular disease.
[13][14]
Antioxidants also have many industrial uses, such as
preservatives in food and cosmetics and to prevent the degradation of rubber and gasoline.
[15]
History[edit]
Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of
unsaturated fats, which is the cause of
rancidity.
[18] Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of
vitamins A,
C, and
E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of
living organisms.
[19][20] The possible
mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized.
[21] Research into how
vitamin E prevents the process of
lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by
scavenging reactive oxygen species before they can damage cells.
[22]
Oxidative challenge in biology[edit]
A
paradox in
metabolism is that, while the vast majority of complex
life on Earthrequires
oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing
reactive oxygen species.
[23]Consequently, organisms contain a complex network of antioxidant
metabolitesand
enzymes that work together to prevent oxidative damage to cellular components such as
DNA,
proteins and
lipids.
[1][24] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.
[1][23] However, reactive oxygen species also have useful cellular functions, such as
redox signaling. Thus, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.
[25]
The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.
[31] In this process, the superoxide anion is produced as a
by-product of several steps in the
electron transport chain.
[32]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 oxygen and form the superoxide anion, instead of moving through the normal series of well-controlled reactions of the electron transport chain.
[33] Peroxide is also produced from the oxidation of reduced
flavoproteins, such as
complex I.
[34]However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.
[35][36] In plants,
algae, and
cyanobacteria, reactive oxygen species are also produced during
photosynthesis,
[37] particularly under conditions of high
light intensity.
[38] This effect is partly offset by the involvement of
carotenoids in
photoinhibition, and in algae and cyanobacteria, by large amount of
iodideand
selenium,
[39] which involves these antioxidants reacting with over-reduced forms of the
photosynthetic reaction centres to prevent the production of reactive oxygen species.
[40][41]
Metabolites[edit]
Overview[edit]
Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (
hydrophilic) or in lipids (
lipophilic). In general, water-soluble antioxidants react with oxidants in the cell
cytosol and the
blood plasma, while lipid-soluble antioxidants protect
cell membranes from lipid peroxidation.
[1] These compounds may be synthesized in the body or obtained from the diet.
[24] 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 (see table below). Some antioxidants are only found in a few organisms and these compounds can be important in
pathogens and can be
virulence factors.
[42]
The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having
synergistic and interdependent effects on one another.
[43][44] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.
[24]The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.
[24]
Some compounds contribute to antioxidant defense by
chelating transition 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.
[36] 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, as is discussed below.
