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  1. 1. Contents:-AntioxidantsThe oxidative challenge in biologyMetabolitesUric acidAscorbic acidPro-oxidant activitiesPotential of antioxidant supplements to damage health 1
  2. 2. AntioxidantsAn antioxidant is a molecule capable of inhibiting the oxidation of othermolecules. Oxidation is a chemical reaction that transfers electrons orhydrogen from a substance to an oxidizing agent. Oxidation reactions canproduce free radicals. In turn, these radicals can start chain reactions. Whenthe chain reaction occurs in a cell, it can cause damage or death to the cell.Antioxidants terminate these chain reactions by removing free radicalintermediates, and inhibit other oxidation reactions. They do this by beingoxidized themselves, so antioxidants are often reducing agents such asthiols, ascorbic acid, or polyphenols.Antioxidants are important additives in gasoline. These antioxidants preventthe formation of gums that interfere with the operation of internalcombustion engines.Although oxidation reactions are crucial for life, they can also be damaging;plants and animals maintain complex systems of multiple types ofantioxidants, such as glutathione, vitamin C, and vitamin E as well asenzymes such as catalase, superoxide dismutase and various peroxidases.Low levels of antioxidants, or inhibition of the antioxidant enzymes, causeoxidative stress and may damage or kill cells.Antioxidants are widely used in dietary supplements and have beeninvestigated for the prevention of diseases such as cancer, coronary heartdisease and even altitude sickness. Although initial studies suggested thatantioxidant supplements might promote health, later large clinical trials witha limited number of antioxidants detect no benefit and even suggested thatexcess supplementation with certain putative antioxidants may be harmful.Antioxidants also have many industrial uses, such as preservatives in foodand cosmetics and to prevent the degradation of rubber and gasoline. 2
  3. 3. The oxidative challenge in biologyA paradox in metabolism is that, while the vast majority of complex life onEarth requires oxygen for its existence, oxygen is a highly reactive moleculethat damages living organisms by producing reactive oxygen species.Consequently, organisms contain a complex network of antioxidantmetabolites and enzymes that work together to prevent oxidative damage tocellular 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.However, reactive oxygen species also have useful cellular functions, suchas redox signaling. Thus, the function of antioxidant systems is not toremove oxidants entirely, but instead to keep them at an optimum level.The reactive oxygen species produced in cells include hydrogen peroxide(H2O2), hypochlorous acid (HClO), and free radicals such as the hydroxylradical (·OH) and the superoxide anion (O2−). The hydroxyl radical isparticularly unstable and will react rapidly and non-specifically with mostbiological molecules. This species is produced from hydrogen peroxide inmetal-catalyzed redox reactions such as the Fenton reaction. These oxidantscan damage cells by starting chemical chain reactions such as lipidperoxidation, or by oxidizing DNA or proteins. Damage to DNA can causemutations and possibly cancer, if not reversed by DNA repair mechanisms,while damage to proteins causes enzyme inhibition, denaturation and proteindegradation.MetabolitesAntioxidants are classified into two broad divisions, depending on whetherthey are soluble in water (hydrophilic) or in lipids (hydrophobic). In general,water-soluble antioxidants react with oxidants in the cell cytosol and theblood plasma, while lipid-soluble antioxidants protect cell membranes fromlipid peroxidation. These compounds may be synthesized in the body orobtained from the diet. The different antioxidants are present at a wide range 3
  4. 4. of concentrations in body fluids and tissues, with some such as glutathioneor ubiquinone mostly present within cells, while others such as uric acid aremore evenly distributed (see table below). Some antioxidants are only foundin a few organisms and these compounds can be important in pathogens andcan be virulence factors.The relative importance and interactions between these differentantioxidants is a very complex question, with the various metabolites andenzyme systems having synergistic and interdependent effects on oneanother. The action of one antioxidant may therefore depend on the properfunction of other members of the antioxidant system. The amount ofprotection provided by any one antioxidant will also depend on itsconcentration, its reactivity towards the particular reactive oxygen speciesbeing considered, and the status of the antioxidants with which it interacts.Uric acidUric acid is by-far the highest concentration antioxidant in human blood.Uric acid (UA) is an antioxidant oxypurine produced from xanthine by theenzyme xanthine oxidase, and is an intermediate product of purinemetabolism. In almost all land animals, urate oxidase further catalyzes theoxidation of uric acid to allantoin, but in humans and most higher primates,the urate oxidase gene is nonfunctional, so that UA is not further brokendown. The evolutionary reasons for this loss of urate converstion to allantoinremain the topic of active speculation. The antioxidant effects of uric acidhave led researchers to suggest this mutation was beneficial to earlyprimates and humans Studies of high altitude acclimatization support thehypothesis that urate acts as an antioxidant by mitigating the oxidative stresscaused by high-altitude hypoxia. In animal studies that investigate diseasesfacilitated by oxidative stress, introduction of UA both prevents the diseaseor reduces it, leading researchers to propose this is due to UAs antioxidantproperties. Studies of UAs antioxidant mechanism support this proposal. 4
  5. 5. With respect to multiple sclerosis, Gwen Scott explains the significance ofuric acid as an antioxidant by proposing that "Serum UA levels are inverselyassociated with the incidence of MS in humans because MS patients havelow serum UA levels and individuals with hyperuricemia (gout) rarelydevelop the disease. Moreover, the administration of UA is therapeutic inexperimental allergic encephalomyelitis (EAE), an animal model of MS." Insum, while the mechanism of UA as an antioxidant is well-supported, theclaim that its levels affect MS risk is still controversial, and requires moreresearch.Ascorbic acidAscorbic acid or "vitamin C" is a monosaccharide oxidation-reduction(redox) catalyst found in both animals and plants. As one of the enzymesneeded to make ascorbic acid has been lost by mutation during primateevolution, humans must obtain it from the diet; it is therefore a vitamin.Most other animals are able to produce this compound in their bodies and donot require it in their diets. Ascorbic acid is required for the conversion ofthe procollagen to collagen by oxidizing proline residues to hydroxyproline.In other cells, it is maintained in its reduced form by reaction withglutathione, which can be catalysed by protein disulfide isomerase andglutaredoxins. Ascorbic acid is redox catalyst which can reduce, and therebyneutralize, reactive oxygen species such as hydrogen peroxide. In addition toits direct antioxidant effects, ascorbic acid is also a substrate for the redoxenzyme ascorbate peroxidase, a function that is particularly important instress resistance in plants. Ascorbic acid is present at high levels in all partsof plants and can reach concentrations of 20 millimolar in chloroplasts.Pro-oxidant activitiesAntioxidants that are reducing agents can also act as pro-oxidants. Forexample, vitamin C has antioxidant activity when it reduces oxidizing 5
  6. 6. substances such as hydrogen peroxide, however, it will also reduce metalions that generate free radicals through the Fenton reaction. 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 ofantioxidants are an area of current research, but vitamin C, which exerts itseffects as a vitamin by oxidizing polypeptides, appears to have a mostlyantioxidant action in the human body. However, less data is available forother dietary antioxidants, such as vitamin E, or the polyphenols. Likewise,the pathogenesis of diseases involving hyperuricemia likely involve uricacids direct and indirect pro-oxidant properties.Potential of antioxidant supplements to damage healthSome antioxidant supplements may promote disease and increase mortalityin humans. Hypothetically, free radicals induce an endogenous responsewhich protects against exogenous radicals (and possibly other toxiccompounds). Recent experimental evidence strongly suggests that this isindeed the case, and that such induction of endogenous free radicalproduction extends the life span of Caenorhabditis elegans. Mostimportantly, this induction of life span is prevented by antioxidants,providing direct evidence that toxic radicals may mitohormetically exert lifeextending and health promoting effects. 6
  7. 7. References1- Werner Dabelstein, Arno Reglitzky, Andrea Schütze and Klaus Reders"Automotive Fuels" in Ullmanns Encyclopedia of Industrial Chemistry2007,2- Benzie, I (2003). "Evolution of dietary antioxidants". ComparativeBiochemistry and Physiology 136 (1): 113–26.3- Venturi, Sebastiano; Donati, Francesco M.; Venturi, Alessandro; Venturi,Mattia (2000).4- Moureu, Charles; Dufraisse, Charles (1922). "Sur lautoxydation: Lesantioxygènes" (in French).5- Davies, KJ (1995). "Oxidative stress: The paradox of aerobic life".Biochemical Society Symposia 61: 1–31 7