Space-filling model of the antioxidant metabolite glutathione. Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl 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. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state

An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. In Chemistry, a molecule is defined as a sufficiently stable electrically neutral group of at least two Atoms in a definite arrangement held together by Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. A chemical reaction is a process that always results in the interconversion of Chemical substances The substance or substances initially involved in a chemical reaction are called The electron is a fundamental Subatomic particle that was identified and assigned the negative charge in 1897 by J An oxidizing agent or oxidising agent (also called an oxidant, oxidizer or oxidiser) can be defined as either a Chemical compound Oxidation reactions can produce free radicals, which start chain reactions that damage cells. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell A chain reaction is a sequence of Reactions where a reactive product or by-product causes additional reactions to take place The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols or polyphenols. A reducing agent (also called a reductant or reducer) is the element or a compound in a Redox (reduction-oxidation reaction (see Electrochemistry In Organic chemistry, a thiol is a compound that contains the functional group composed of a Sulfur atom and a Hydrogen atom (-SH Polyphenols are a group of chemical substances found in plants characterized by the presence of more than one Phenol unit or building block per molecule

Although oxidation reactions are crucial 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. Plants are living Organisms belonging to the kingdom Plantae. Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl Vitamin C or L-ascorbate is an Essential nutrient for a large number of higher primate species a small number of other Mammalian See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. Peroxidases ( EC number 1111x are a large family of Enzymes A majority of peroxidase protein sequences can be found in the PeroxiBase database Low levels of antioxidants, or inhibition of the antioxidant enzymes, causes oxidative stress and may damage or kill cells. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. Pharmacology (from Greek grc φάρμακον pharmakon, "drug" and grc -λογία -logia) is the study of how Drugs A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Neurodegenerative Disease ( Greek νέυρο- néuro-, "nerval" and Latin dēgenerāre, "to decline" or "to However, it is unknown whether oxidative stress is the cause or the consequence of disease. 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. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Coronary disease (or coronary heart disease) refers to the failure of Coronary circulation to supply adequate circulation to Cardiac muscle and surrounding 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 be harmful. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices ^[1] 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 preservative is a natural or synthetic chemical that is added to products such as foods pharmaceuticals paints biological samples wood etc

History

The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th century, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines. Corrosion means the breaking down of essential properties in a material due to Chemical reactions with its surroundings Vulcanization (or Vulcanisation refers to a specific curing process of Rubber involving high heat and the addition of Sulfur or other equivalent curatives In Polymer chemistry, polymerization is a process of reacting Monomer Molecules together in a Chemical reaction to form three-dimensional networks Components subject to fouling The following lists examples of components that may be subject of fouling and the direct effects of fouling heat exchanger surfaces The internal combustion engine is an engine in which the Combustion of Fuel and an Oxidizer (typically air occurs in a confined space called a ^[2]

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. An unsaturated fat is a Fat or Fatty acid in which there are one or more Double bonds in the fatty acid chain Rancidification is the decomposition of Fats Oils and other Lipids by Hydrolysis or Oxidation, or both ^[3] 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 biochemistry of living organisms. Vitamin A refers to a family of similarly shaped molecules the Retinoids. Vitamin C or L-ascorbate is an Essential nutrient for a large number of higher primate species a small number of other Mammalian ^[4][5]

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. In Pharmacology, the term mechanism of action (MOA refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect ^[6] 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. Lipid peroxidation refers to the oxidative degradation of Lipids It is the process whereby free radicals "steal" electrons from the lipids in Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and ^[7]

The oxidative challenge in biology

Further information: Oxidative stress

The structure of the antioxidant vitamin ascorbic acid (vitamin C). Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily A vitamin is an Organic compound required as a Nutrient in tiny amounts by an Organism. This article deals with the molecular aspects of ascorbic acid

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. Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the ^[8] 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. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble ^[9][10] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. ^[9][8]

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⁻). Hydrogen peroxide (H2O2 is a very pale blue liquid which appears colorless in a dilute solution slightly more Viscous than water Hypochlorous acid ( IUPAC name chloric(I acid) is a weak Acid with the Chemical formula HOCl Hydroxyl in Chemistry describes a molecule consisting of an Oxygen atom and a Hydrogen atom joined by a Covalent bond. Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature ^[11] 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. Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst Fenton's reagent is a solution of Hydrogen peroxide and an Iron Catalyst that is used to Oxidize Contaminants or Waste waters ^[12] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins. ^[9] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,^[13][14] while damage to proteins causes enzyme inhibition, denaturation and protein degradation. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome. Denaturation is a process in which Proteins or Nucleic acids lose their structure (tertiary structure by application of some external stress or compound for Proteasomes are large Protein complexes inside all Eukaryotes and Archaea, as well as in some Bacteria. ^[15]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species. ^[16] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain. An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer ^[17] Particularly important is the reduction of coenzyme Q in complex III, since a highly reactive free radical is formed as an intermediate (Q·⁻). Coenzyme Q10 (also known as ubiquinone ubidecarenone coenzyme Q and abbreviated at times to CoQ10 CoQ Q10 or Q is a Benzoquinone, where Q The coenzyme Q: cytochrome c — oxidoreductase, sometimes called the cytochrome bc 1 complex, and at other times complex III 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. ^[18] In a similar set of reactions in plants, reactive oxygen species are also produced during photosynthesis under conditions of high light intensity. Photosynthesis is a Metabolic pathway that converts Light Energy into Chemical energy. ^[19] 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 to prevent the production of reactive oxygen species. Carotenoids are organic Pigments that are naturally occurring in Chromoplasts of plants and some other photosynthetic Organisms Photoinhibition is a reduction in a plant's (or other photosynthetic organism's capacity for Photosynthesis caused by exposure to strong light (above the saturation point A photosynthetic reaction center is a complex of three types of protein that is the site where molecular excitations originating from sunlight are transformed into a series of electron-transfer ^[20]

Metabolites

Overview

Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). Water is a common Chemical substance that is essential for the survival of all known forms of Life. Hydrophile, from the Greek (hydros "water" and φιλια (philia "friendship" refers to a physical property of a Molecule In Chemistry, hydrophobicity (from the combining form of water in Attic Greek hydro- and for fear phobos) refers to the physical property of 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. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer ^[9] These compounds may be synthesized in the body or obtained from the diet. ^[10] 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). Coenzyme Q10 (also known as ubiquinone ubidecarenone coenzyme Q and abbreviated at times to CoQ10 CoQ Q10 or Q is a Benzoquinone, where Q Uric acid (or urate) is an Organic compound of Carbon, Nitrogen, Oxygen and Hydrogen with the formula C5H4N4O3

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. Synergy (from the Greek el-Latn syn-ergo, el συνεργός meaning working together is the term used to describe a situation where the final outcome ^[21][22] The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system. ^[10] 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. ^[10]

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Chelation is the binding or complexation of a bi- or multidentate Ligand. In Chemistry, the term transition metal (sometimes also called a transition element) has two possible meanings It commonly refers to any element in Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin. Iron-binding proteins are Carrier proteins and Metalloproteins which play many important roles in Metabolism. Transferrin is a Blood plasma Protein for Iron Ion delivery Transferrin is a Glycoprotein, which binds iron very tightly but reversibly Ferritin is a Globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both Prokaryotes ^[23] 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. Selenium (səˈliniəm is a Chemical element with the Atomic number 34 represented by the chemical symbol Se, an atomic mass of 78 Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 A chemical element is a type of Atom that is distinguished by its Atomic number; that is by the number of Protons in its nucleus.

Ascorbic acid

Ascorbic acid or "vitamin C" is a monosaccharide antioxidant found in both animals and plants. Retinol (Afaxin, the animal form of Vitamin A, is a fat-soluble vitamin important in vision and Bone growth Tocopherol, a class of chemical compounds of which many have Vitamin E activity describes a series of Organic compounds consisting of various methylated phenols Coenzyme Q10 (also known as ubiquinone ubidecarenone coenzyme Q and abbreviated at times to CoQ10 CoQ Q10 or Q is a Benzoquinone, where Q Monosaccharides (from Greek monos: single sacchar: sugar are the most basic unit of Carbohydrates They consist of one sugar and As it cannot be synthesised in humans and must be obtained from the diet, it is a vitamin. ^[36] Most other animals are able to produce this compound in their bodies and do not require it in their diets. ^[37] In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins. Protein disulfide isomerase or PDI ( is an Enzyme in the Endoplasmic reticulum in eukaryotes or Periplasmic space of prokaryotes that catalyzes Glutaredoxins are small Redox enzymes of approximately one hundred amino-acid residues which use Glutathione as a cofactor ^[38][39] Ascorbic acid is a reducing agent and can reduce and thereby neutralize reactive oxygen species such as hydrogen peroxide. ^[40] In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the antioxidant enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants. Ascorbate peroxidases (or APX) are enzymes that detoxify Peroxides such as Hydrogen peroxide using Ascorbate as a substrate ^[41]

Glutathione

The free radical mechanism of lipid peroxidation. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell

Glutathione is a cysteine-containing peptide found in most forms of aerobic life. Not to be confused with Cystine, its oxidized dimer Cysteine (abbreviated as Cys or C) is an α- Amino acid with Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino ^[42] It is not required in the diet and is instead synthesized in cells from its constituent amino acids. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this ^[43] Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems as well as reacting directly with oxidants. Glutathione reductase, also known as GSR, is a human Gene. The Protein encoded by this gene is an Enzyme ( which reduces Glutathione ^[38] Due to its high concentration and its central role in maintaining the cell's redox state, glutathione is one of the most important cellular antioxidants. ^[42]

Melatonin

Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier. Melatonin is a naturally occurring Hormone found in most animals including humans and some other living organisms including Algae. The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic ^[44] Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation. Pro-oxidants are chemicals that induce Oxidative stress, either through creating Reactive oxygen species or inhibiting Antioxidant systems Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant. ^[45]

Tocopherols and tocotrienols (vitamin E)

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties. See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble Tocotrienols – together with Tocopherols – compose the Vitamin E family ^[46][47] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of ^[48]

It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. ^[46][49] This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol. ^[50]

However, the roles and importance of the various forms of vitamin E are presently unclear,^[51][52] and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism. Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions ^[53][54] The functions of the other forms of vitamin E are even less well-understood, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens,^[48] and tocotrienols may be important in protecting neurons from damage. In Chemistry, a nucleophile (literally nucleus lover as in nucleus and phile) is a Reagent that forms a Chemical bond to In Chemistry, an electrophile (literally electron-lover) is a Reagent attracted to Electrons that participates in a chemical reaction by accepting Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information ^[55]

Pro-oxidant activities

Further information: Pro-oxidant

Antioxidants that are reducing agents can also act as pro-oxidants. Pro-oxidants are chemicals that induce Oxidative stress, either through creating Reactive oxygen species or inhibiting Antioxidant systems For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide,^[56] however, it will also reduce metal ions that generate free radicals through the Fenton reaction. Fenton's reagent is a solution of Hydrogen peroxide and an Iron Catalyst that is used to Oxidize Contaminants or Waste waters ^[57][58]

2 Fe³⁺ + Ascorbate → 2 Fe²⁺ + Dehydroascorbate

2 Fe²⁺ + 2 H₂O₂ → 2 Fe³⁺ + 2 OH· + 2 OH⁻

The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, for example, appears to have a mostly antioxidant action in the body. ^[59][57] However, fewer data are available for other dietary antioxidants, such as vitamin E. ^[60]

Enzyme systems

Enzymatic pathway for detoxification of reactive oxygen species.

Overview

As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes. ^[9][8] Here, the superoxide released by processes such as oxidative phosphorylation is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes to the antioxidant defenses of a cell can be hard to separate from one another, but the generation of transgenic mice lacking just one antioxidant enzyme can be informative. This article is about organisms which have been genetically modified ^[61]

Superoxide dismutase, catalase and peroxiredoxins

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyse the breakdown of the superoxide anion into oxygen and hydrogen peroxide. The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. ^[62][63] SOD enzymes are present in almost all aerobic cells and in extracellular fluids. ^[64] Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, manganese or iron. Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Manganese (ˈmæŋgəniːz is a Chemical element, designated by the symbol Mn. Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 In humans, the copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. ^[63] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites. Extracellular fluid (ECF usually denotes all body fluid outside of cells ^[65] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth. ^[66] In contrast, the mice lacking copper/zinc SOD are viable but have lowered fertility, while mice without the extracellular SOD have minimal defects. ^[61][67] In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in chloroplasts that is absent from vertebrates and yeast. Chloroplasts are Organelles found in Plant cells and eukaryotic Algae that conduct Photosynthesis. Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described ^[68]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor. Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to ^[69][70] This protein is localized to peroxisomes in most eukaryotic cells. Peroxisomes are Ubiquitous Organelles in Eukaryotes that participate in the metabolism of Fatty acids and other metabolites Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex ^[71] Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism. Enzyme kinetics is the study of the Chemical reactions that are catalysed by Enzymes, with a focus on their Reaction rates The study of Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate. ^[72] Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — "acatalasemia" — or mice genetically engineered to lack catalase completely, suffer few ill effects. Acatalasemia a genetic deficiency of erythrocyte Catalase inherited as an autosomal Recessive trait ^[73][74]

Decameric structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium. In Biochemistry, quaternary structure is the arrangement of multiple folded Protein molecules in a multi-subunit complex The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Peroxiredoxins (Prxs EC 111115 are a ubiquitous family of Antioxidant Enzymes that also control Cytokine -induced peroxide levels and thereby mediate Salmonella enterica is a rod shaped Flagellated Gram-negative Bacterium, and a member of the Genus Salmonella ^[75]

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite. Peroxiredoxins (Prxs EC 111115 are a ubiquitous family of Antioxidant Enzymes that also control Cytokine -induced peroxide levels and thereby mediate Organic peroxides are Organic compounds containing the Peroxide Functional group (ROOR' Peroxynitrite is the Anion with the formula ONOO− It is an unstable "valence isomer" of Nitrate, NO3− which has the ^[76] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins. ^[77] These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate. A sulfenic acid is an Organosulfur compound and Oxoacid with the general formula R[[sulfur S]] O[[hydrogen H]] where R ≠ H ^[78] Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts. Hemolytic anemia is Anemia due to Hemolysis, the abnormal breakdown of Red blood cells (RBCs either in the Blood vessels (intravascular hemolysis ^[79][80][81]

Thioredoxin and glutathione systems

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase. Thioredoxins are Proteins that act as antioxidants by facilitating the reduction of other proteins by Cysteine Thiol-disulfide exchange. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express Thioredoxin Reductase (TR TrxR ( are the only known enzymes to reduce Thioredoxin (Trx ^[82] Proteins related to thioredoxin are present in all sequenced organisms, with plants such as Arabidopsis thaliana having a particularly great diversity of isoforms. Arabidopsis thaliana ( A-ra-bi-dóp-sis tha-li-á-na; thale cress, mouse-ear cress or Arabidopsis) is a small ^[83] The active site of thioredoxin consists of two neighboring cysteines, as part of a highly-conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In Chemistry vicinal (from Latin vicinus = neighbour stands for any two Functional groups bonded to two adjacent Carbon atoms In Genetics, a sequence motif is a Nucleotide or amino-acid Sequence pattern that is widespread and has or is conjectured to have a biological In Chemistry, a disulfide usually refers to the structural unit composed of a linked pair of sulfur atoms In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state. ^[84] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor. Nicotinamide adenine dinucleotide phosphate ( NADP+, in older notation triphosphopyridine nucleotide TPN) is used in anabolic reactions such as Lipid ^[85]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases. Glutathione peroxidase () is the general name of an Enzyme family with Peroxidase activity whose main biological role is to protect the organism from oxidative damage ^[42] This system is found in animals, plants and microorganisms. ^[86][42] Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. Selenium (səˈliniəm is a Chemical element with the Atomic number 34 represented by the chemical symbol Se, an atomic mass of 78 There are at least four different glutathione peroxidase isozymes in animals. Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction ^[87] Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme have normal lifespans,^[88] but they are hypersensitive to induced oxidative stress. ^[89] In addition, the glutathione S-transferases are another class of glutathione-dependent antioxidant enzymes that show high activity with lipid peroxides. The glutathione S -transferase (GST family of Enzymes comprises a long list of Cytosolic, Mitochondrial, and Microsomal ^[90] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism. Detoxification, or detox for short is the removal of Toxic substances from the body ^[91]

Oxidative stress in disease

Further information: Pathology, Free-radical theory of aging

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease,^[92][93] Parkinson's disease,^[94] the pathologies caused by diabetes,^[95][96] rheumatoid arthritis,^[97] and neurodegeneration in motor neurone diseases. Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and The free-radical theory of aging states that organisms age because cells accumulate Free radical damage over Time. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Neurodegeneration is progressive loss of structure or function of Neurons including death of neurons The motor neurone diseases (or motor neuron diseases) (MND are a group of progressive neurological disorders that destroy Motor neurones the cells that control voluntary ^[98] In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a consequence of the disease and cause the disease symptoms;^[11] as a plausible alternative, a neurodegenerative disease might result from defective axonal transport of mitochondria, which carry out oxidation reactions. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Axoplasmic transport, also called axonal transport, is responsible for movement of mitochondria, Lipids Synaptic vesicles Proteins One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease. Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation ^[99][100]

A low calorie diet extends median and maximum lifespan in many animals. Calorie restriction, or caloric restriction (CR aims to improve health and slow the aging process by limiting dietary energy intake This effect may involve a reduction in oxidative stress. ^[101] While there is good evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,^[102][103] the evidence in mammals is less clear. Drosophila melanogaster (from the Greek for black-bellied dew-lover) is a two-winged insect that belongs to the Diptera, the order Caenorhabditis elegans (ˌsiːnoʊræbˈdaɪtɪs ˈɛlɪgænz is a free-living Nematode (roundworm about 1  mm in length which ^{[104][105][106]} Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging, however antioxidant vitamin supplementation has no detectable effect on the aging process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents. ^[107][108] One reason for this might be the fact that consuming antioxidant molecules such as polyphenols and vitamin E will produce changes in other parts of metabolism, so it may be these other non-antioxidant effects that are the real reason they are important in human nutrition. ^[109][53]

Health effects

Disease treatment

The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain ^[110] Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Here, superoxide dismutase mimetics,^[111] sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury,^[112] while the experimental drug NXY-059^[113][114] and ebselen^[115] are being applied in the treatment of stroke. The fictional truth drug Hyoscine-pentothal does not describe real pentothal accurately Propofol is a short-acting Intravenous sedative agent used for the induction of general Anesthesia for adults and children maintenance of general anesthesia and Reperfusion injury refers to damage to tissue caused when Blood supply returns to the tissue after a period of Ischemia. Traumatic brain injury (TBI also called intracranial injury, occurs when Physical trauma injures the Brain. Disufenton sodium ( NXY-059) is the disulfonyl derivative of the neuroprotective spintrap Phenylbutynitrone or "PBN" Ebselen or 2-phenyl-1 2-benzisoselenazol-3(2H-one (also called PZ 51 or DR3305) is a mimic of Glutathione peroxidase and can also react These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis,^[116][117] and as a way to prevent noise-induced hearing loss. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Amyotrophic Lateral Sclerosis ( ALS, sometimes called Maladie de Charcot, or in the United States Lou Gehrig's Disease) is a progressive Noise-induced hearing loss (NIHL is an increasingly prevalent disorder that results from exposure to high-intensity Sound, especially over a long period of time ^[118]

Disease prevention

Structure of the polyphenol antioxidant resveratrol. A polyphenol antioxidant is a type of Antioxidant containing a Polyphenolic substructure Resveratrol is a Phytoalexin produced naturally by several Plants when under attack by Pathogens such as Bacteria or Fungi

Antioxidants can cancel out the cell-damaging effects of free radicals. ^[9] Furthermore, people who eat fruits and vegetables, which are good sources of antioxidants, have a lower risk of heart disease and some neurological diseases,^[119] and there is evidence that some types of vegetables, and fruits in general, probably protect against a number of cancers. ^[120] These observations suggested that antioxidants might help prevent these conditions. There is some evidence that antioxidants might help prevent diseases such as macular degeneration,^[121] suppressed immunity due to poor nutrition,^[122] and neurodegeneration. Macular degeneration is a medical condition usually of older adults which results in a loss of vision in the center of the visual field (the Macula) because An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor ^[123] However, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no reduction in either the risk of developing heart disease, or the rate of progression of existing disease. ^[124][125] This suggests that other substances in fruit and vegetables (possibly flavonoids), or a complex mix of substances, may contribute to the better cardiovascular health of those who consume more fruit and vegetables. The term flavonoid (or bioflavonoid refers to a class of Plant Secondary metabolites According to the IUPAC nomenclature they can be classified into ^[126][127]

It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease. ^[128] Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease. ^[129] It is not clear if the doses used in these trials or in most dietary supplements are capable of producing any significant decrease in oxidative stress. ^[130]

While several trials have investigated supplements with high doses of antioxidants, the "Supplémentation en Vitamines et Mineraux Antioxydants" (SU. VI. MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet. ^[131] Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc) or placebo pills for an average of 7. Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity 5 years. The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, a subgroup analysis showed a 31% reduction in the risk of cancer in men, but not women.

Many nutraceutical and health food companies now sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries. Nutraceutical, a Portmanteau of Nutrition and Pharmaceutical, refers to extracts of foods claimed to have a medicinal effect on human health ^[132] These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds), combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or herbs that contain antioxidants - such as green tea and jiaogulan. Green tea is a type of Tea made solely with the leaves of Camellia sinensis, that has undergone minimal Oxidation during processing Gynostemma pentaphyllum, also called jiaogulan ( literally "twisting-vine-orchid" Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether antioxidant supplementation is beneficial, and if so, which antioxidant(s) are beneficial and in what amounts. ^{[133][134][119]}

It has been suggested that moderate levels of oxidative stress may increase life expectancy in the worm Caenorhabditis elegans, by inducing a protective response to increased levels of reactive oxygen species. ^[135] However, the suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae,^[136] and the situation in mammals is even less clear. Saccharomyces cerevisiae is a Species of Budding Yeast. It is perhaps the most useful Yeast owing to its use since ancient times ^{[104][137][138]}

Physical exercise

During exercise, oxygen consumption can increase by a factor of more than 10. ^[139] This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens The immune system response to damage done by exercise peaks 2 to 7 days after exercise, the period during which adaptation resulting in greater fitness is greatest. During this process, free radicals are produced by neutrophils to remove damaged tissue. Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the As a result, excessive antioxidant levels have the potential to inhibit recovery and adaptation mechanisms. ^[140]

The evidence for benefits from antioxidant supplementation in vigorous exercise is mixed. There is strong evidence that one of the adaptations resulting from exercise is a strengthening of the body's antioxidant defenses, particularly the glutathione system, to deal with the increased oxidative stress. ^[141] It is possible that this effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise. ^[142]

However, no benefits to athletes are seen with vitamin A or E supplementation. ^[143] For example, despite its key role in preventing lipid membrane peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners. ^[144] Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage. ^[145][146] However, other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery. ^[147]

Adverse effects

Further information: Micronutrients

Structure of the metal chelator phytic acid. Micronutrients are Nutrients needed for life in small quantities IP6 redirects here For the Internet Protocol see IPv6 Phytic acid (known as Inositol hexakisphosphate (IP6, or

Relatively strong reducing acids can have anti-nutritional effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed. ^[148] Notable examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets. Oxalic acid is the Chemical compound with the formula H2C2O4 This Dicarboxylic acid is better described with the Tannins are Astringent, bitter plant Polyphenols that either bind and Precipitate or shrink Proteins The astringency from the tannins is what IP6 redirects here For the Internet Protocol see IPv6 Phytic acid (known as Inositol hexakisphosphate (IP6, or ^[149] Calcium and iron deficiencies are not uncommon in diets in developing countries where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain bread. Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Developing countries are countries that haven't reached Western-style standards of democratic government free market economy industrialization social programs and human rights guaranties Whole grains are cereal grains that Bran and germ as well as the Endosperm, in contrast to Refined grains, which retain only ^[150]

Nonpolar antioxidants such as eugenol, a major component of oil of cloves have toxicity limits that can be exceeded with the misuse of undiluted essential oils. Tannins are Astringent, bitter plant Polyphenols that either bind and Precipitate or shrink Proteins The astringency from the tannins is what "Polar molecule" and "Non-polar" redirect here Eugenol (C10H12O2 is an allyl chain-substituted Guaiacol. Eugenol is a member of the Phenylpropanoids class of chemical compounds Oil of cloves, also known as Clove oil, is an Essential oil from the Clove plant Syzygium aromaticum. An essential oil is a concentrated Hydrophobic Liquid containing volatile Aroma compounds from Plants They are also known as volatile ^[154] Toxicity associated with high doses of water-soluble antioxidants such as ascorbic acid are less of a concern, as these compounds can be excreted rapidly in urine. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. ^[155] More seriously, very high doses of some antioxidants may have harmful long-term effects. The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer patients found that smokers given supplements containing beta-carotene and vitamin A had increased rates of lung cancer. ^[156] Subsequent studies confirmed these adverse effects. ^[157]

These harmful effects may also be seen in non-smokers, as a recent meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality but saw no significant effect from vitamin C. ^[158] No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected only when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people, or people already suffering disease, these results may not apply to the general population. ^[159] This meta-analysis was later repeated and extended by the same authors, with the new analysis published by the Cochrane Collaboration; confirming the previous results. The Cochrane Collaboration is a group of over 11500 volunteers in more than 90 countries who apply a rigorous systematic process to review the effects of interventions tested in biomedical ^[160] These two publications are consistent with some previous meta-analyzes that also suggested that Vitamin E supplementation increased mortality,^[161] and that antioxidant supplements increased the risk of colon cancer. ^[162] However, the results of this meta-analysis are inconsistent with other studies such as the SU. VI. MAX trial, which suggested that antioxidants have no effect on cause-all mortality. ^{[131][163][164][165]} Overall, the large number of clinical trials carried out on antioxidant supplements suggest that either these products have no effect on health, or that they cause a small increase in mortality in elderly or vulnerable populations. ^{[133][119][158]}

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, it has been proposed that antioxidants may, paradoxically, interfere with cancer treatments. ^[166] This was thought to occur since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments. As a result, by reducing the redox stress in cancer cells, antioxidant supplements were thought to decrease the effectiveness of radiotherapy and chemotherapy. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. ^[167] However, this concern appears not to be valid, as it has been addressed by multiple clinical trials that indicate that antioxidants are either neutral or beneficial in cancer therapy. ^[168][169]

Measurement and levels in food

Further information: List of antioxidants in food, Polyphenol antioxidants

Fruits and vegetables are good sources of antioxidants. Vitamins Vitamin A (retinol also synthesized by the body from Beta-carotene, protects dark green yellow and orange vegetables and fruits from A polyphenol antioxidant is a type of Antioxidant containing a Polyphenolic substructure The term fruit has different meanings dependent on context and the term is not synonymous in Food preparation and Biology. The term " vegetable " generally means the edible parts of Plants The definition of the word is traditional rather than Scientific, however

Measurement of antioxidants is not a straightforward process, as this is a diverse group of compounds with different reactivities to different reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives. Food science is a discipline concerned with all technical aspects of Food, beginning with Harvesting or slaughtering, and ending with its Cooking Oxygen Radical Absorbance Capacity ( ORAC) is a method of measuring Antioxidant capacities of different foods ^[170][171] Other measurement tests include the Folin-Ciocalteu reagent, and the trolox equivalent antioxidant capacity assay. The Folin-Ciocalteu reagent (FCR or Folin's phenol reagent or Folin-Denis reagent is a mixture of phosphomolybdate and phosphotungstate used for the colorimetric Oxygen Radical Absorbance Capacity ( ORAC) is a method of measuring Antioxidant capacities of different foods ^[172] In medicine, a range of different assays are used to assess the antioxidant capability of blood plasma and of these, the ORAC assay may be the most reliable. ^[173]

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, legumes and nuts. Some antioxidants such as lycopene and ascorbic acid can be destroyed by long-term storage or prolonged cooking. Lycopene is a bright red Carotenoid pigment and Phytochemical found in Tomatoes and other red fruits ^[174][175] Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea. ^[176][177] In general, processed foods contain less antioxidants than fresh and uncooked foods, since the preparation processes may expose the food to oxygen. ^[178]

Some antioxidants are made in the body and are not absorbed from the intestine. Carotenoids are organic Pigments that are naturally occurring in Chromoplasts of plants and some other photosynthetic Organisms In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists One example is glutathione, which is made from amino acids. As any glutathione in the gut is broken down to free cysteine, glycine and glutamic acid before being absorbed, even large oral doses have little effect on the concentration of glutathione in the body. Glycine (abbreviated as Gly or G) is the Organic compound with the formula NH2CH2COOH Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its ^[181] Ubiquinol (coenzyme Q) is also poorly absorbed from the gut and is made in humans through the mevalonate pathway. Coenzyme Q10 (also known as ubiquinone ubidecarenone coenzyme Q and abbreviated at times to CoQ10 CoQ Q10 or Q is a Benzoquinone, where Q The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD route, is an important cellular Metabolic pathway present ^[35]

Uses in technology

Food preservatives

Antioxidants are used as food additives to help guard against food deterioration. Food additives are substances added to food to preserve flavour or improve its taste and appearance A preservative is a natural or synthetic chemical that is added to products such as foods pharmaceuticals paints biological samples wood etc Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers. However, as oxygen is also important for plant respiration, storing plant materials in anaerobic conditions produces unpleasant flavors and unappealing colors. In Animal physiology, respiration is the transport of Oxygen from the outside air to the cells within tissues and the transport of Carbon dioxide ^[182] Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or fungal spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ ^[183] These preservatives include ascorbic acid (AA, E300), propyl gallate (PG, E310), tocopherols (E306), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321). Propyl gallate, or propyl 345-trihydroxybenzoate is an Ester formed by the Condensation of Gallic acid and propanol. tert -Butylhydroquinone ( TBHQ, tertiary butylhydroquinone) is an Aromatic Organic compound which is a type of phenol E320 redirects here For the automobile see Mercedes-Benz E-Class. Butylated hydroxytoluene (BHT also known as Butylhydroxytoluene, is a Lipophilic (fat-soluble Organic compound that is primarily used as an ^[184][185]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid. Rancidification is the decomposition of Fats Oils and other Lipids by Hydrolysis or Oxidation, or both ^[186] Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfurous flavors, it is important to avoid oxidation in fat-rich foods. Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking, salting or fermenting. Smoking is the process of flavoring, Cooking, or preserving Food by exposing it to the Smoke from burning or smoldering plant materials Salting is the preservation of Food with salt. It is related to Pickling (preparing food with brine rather than dry salt Fermentation in Food processing typically refers to the conversion of Sugar to Alcohol using Yeast under Anaerobic conditions Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil or kept in metal containers. WikipediaManual of Style#National varieties of English --> Aluminium foil (known Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation. ^[187]

Industrial uses

Some antioxidants are added to industrial products. A common use is as stabilizers in fuels and lubricants to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues. Gasoline additives increase Gasoline 's Octane rating or act as Corrosion inhibitors or lubricators, thus allowing the use of higher Compression Fuel is any material that is burned or altered in order to obtain energy A lubricant (sometimes referred to as a "Lube" is a substance (often a liquid introduced between two moving surfaces to reduce the Friction between them improving ^[188] They are also used to prevent the oxidative degradation of rubber, plastics and adhesives that causes a loss of strength and flexibility in these materials. Plastic is the general common term for a wide range of synthetic or semisynthetic organic solid materials suitable for the manufacture of industrial products Glue or adhesive is a compound that adheres or bonds two items together ^[189] Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity. Lipstick is a cosmetic product containing pigments oils waxes and emollients that applies color and texture to the lips. Moisturisers or moisturizers (see spelling differences) are complex mixtures of chemical agents specially designed to make the external layers of the Skin

See also

• Evolution of dietary antioxidants
• Free radical theory
• Life extension
• Nootropics
• Nutrition
• Phytochemical
• Mitohormesis
• List of phytochemicals and foods in which they are prominent
• Polymer degradation
• Forensic polymer engineering

Further reading

• Nick Lane Oxygen: The Molecule That Made the World (Oxford University Press, 2003) ISBN 0-198-60783-0
• Barry Halliwell and John M. NN'-Di-2-butyl-14-phenylenediamine is an aromatic Amine used industrially as an Antioxidant to prevent degradation of turbine oils Transformer oils Transformer oil is usually a highly- refined Mineral oil that is stable at high temperatures and has excellent electrical insulating properties Hydraulic fluids are a large group of fluids used as the motive medium in Hydraulic machinery. Wax has traditionally referred to a substance that is secreted by Bees ( Beeswax) and used by them in constructing their Although the word grease originally described the rendered fat of animals the term is now applied more broadly to mean a Lubricant of higher initial Viscosity Butylated hydroxytoluene (BHT also known as Butylhydroxytoluene, is a Lipophilic (fat-soluble Organic compound that is primarily used as an 24-Dimethyl-6- tert -butylphenol is an Alkylated Phenol used industrially as an Antioxidant, eg Jet fuel is a type of Aviation fuel designed for use in Aircraft powered by gas-turbine engines. 26-Di- tert -butylphenol ( 26-DTBP) is an Alkylated Phenol industrially used as an UV stabilizer and an Antioxidant Aviation fuel is a specialized type of Petroleum -based fuel used to power Aircraft. The evolution of oxygen-producing cells was probably one of the most significant events in the history of life The free-radical theory of aging states that organisms age because cells accumulate Free radical damage over Time. Life extension refers to an increase in maximum or average lifespan, especially in humans by slowing down or reversing the processes of aging. '''Nootropics''' popularly referred to as " smart drugs " " smart nutrients " " cognitive enhancers " and " brain enhancers Nutrition (also called nourishment or aliment) is the provision to cells and Organisms of the materials necessary (in the form of food to support Phytochemicals are plant-derived chemical compounds under scientific research for their potential health-promoting properties but with unproved benefits Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is While there is ample evidence to support the health benefits of diets rich in fruits vegetables legumes whole grains and nuts evidence that these effects are due to specific nutrients or Polymer degradation is a change in the properties - Tensile strength, Colour, shape etc - of a Polymer or polymer based product under the influence of The study of failure in Polymeric products is called forensic polymer engineering. C. Gutteridge Free Radicals in Biology and Medicine(Oxford University Press, 2007) ISBN 0-198-56869-X
• Jan Pokorny, Nelly Yanishlieva and Michael H. Gordon Antioxidants in Food: Practical Applications (CRC Press Inc, 2001) ISBN 0-849-31222-1

External links

• Foods that are rich in antioxidants
• U.S. National Institute Health, Office on Dietary Supplements
• List of antioxidants, food sources, and Potential Benefits
• MedlinePlus: Antioxidants.

References