Antioxidant mechanisms -
vitamin E, carotenoids, and lipoic acid are predominantly located in cell membranes. The antioxidants can also be categorized according to their size, the small-molecule antioxidants and large-molecule antioxidants.
The small-molecule antioxidants neutralize the ROS in a process called radical scavenging and carry them away. The main antioxidants in this category are vitamin C, vitamin E, carotenoids, and glutathione GSH. The large-molecule antioxidants are enzymes SOD, CAT, and GSHPx and sacrificial proteins albumin that absorb ROS and prevent them from attacking other essential proteins.
To understand the mechanism of action of antioxidants, it is necessary to understand the generation of free radicals and their damaging reactions. This review elaborates the generation and damages that free radicals create, mechanism of action of the natural antioxidant compounds and assays for the evaluation of their antioxidant properties.
The reaction mechanisms of the antioxidant assays are discussed. The scope of this article is limited to the natural antioxidants and the in vitro assays for evaluation of their antioxidant properties. These ROS can act by either of the two oxygen dependent mechanisms resulting in the destruction of the microorganism or other foreign matter.
The reactive species can also be generated by the myeloperoxidase—halide—H 2 O 2 system. The enzyme myeloperoxidase MPO is present in the neutrophil cytoplasmic granules. In presence of the chloride ion, which is ubiquitous, H 2 O 2 is converted to hypochlorous HOCl, eqn 3 , a potent oxidant and antimicrobial agent.
The enzyme nitric oxide synthase produce reactive nitrogen species RNS , such as nitric oxide NO˙ from arginine eqn 6. Peroxynitrite reacts with the aromatic amino acid residues in the enzyme resulting in the nitration of the aromatic amino acids. Such a change in the aminoacid residue can result in the enzyme inactivation.
However, nitric oxide is an important cytotoxic effector molecule in the defense against tumor cells, various protozoa, fungi, helminthes, and mycobacteria.
The general process of lipid peroxidation can be envisaged as depicted bellow eqn 8 — 11 , where LH is the target PUFA and R˙ is the initializing, oxidizing radical.
Oxidation of the PUFA generates a fatty acid radical L˙ eqn 8 , which rapidly adds oxygen to form a fatty acid peroxyl radical LOO˙, eqn 9. The peroxyl radicals are the carriers of the chain reactions. The peroxyl radicals can further oxidize PUFA molecules and initiate new chain reactions, producing lipid hydroperoxides LOOH eqn 10 and 11 that can break down to yet more radical species.
Lipid hydroperoxides always break down to aldehydes. Many of these aldehydes are biologically active compounds, which can diffuse from the original site of attack and spread the attack to the other parts of the cell.
The ˙OH is highly reactive and reacts with biological molecules such as DNAs, proteins, and lipids, which results in the chemical modifications of these molecules.
There are several research reports on the oxidative damage of DNA due to the ˙OH. The ˙OH reacts with the basepairs of DNA, resulting in the oxidative damage of the heterocyclic moiety and the sugar moiety in the oligonucleotides by a variety of mechanisms.
This type of oxidative damage to DNA is highly correlated to the physiological conditions such as mutagenesis, carcinogenesis, and aging. As shown in the Scheme 1 , the ˙OH reacts with the guanine of the DNA to produce the Chydroxy-adduct radical of guanine, which is converted to the 2,6-diaminohydroxyformamidopyrimidine upon reduction and ring opening reactions.
However, the Chydroxy-adduct radical of guanine is converted to the 8-hydroxyguanine upon oxidation reaction. The ˙OH radical reacts with the heterocyclic moiety of the thymine and cytosine at C5- and C6-positions, resulting in the C5—OH and C6—OH adduct radicals, respectively. The oxidation reaction of these adduct radicals with water followed by deprotonation results in the formation of the cytosine glycol and thymine glycol, respectively.
As shown in the Scheme 2 , the ˙OH reacts with the sugar moiety of DNA by abstracting an H-atom from rom C5 carbon atom. The reactions of carbon-centered sugar radicals result in the DNA strand breaks and base-free sites by a variety of mechanisms.
The amino acid's lysine, proline, histidine, and arginine have been found to be the most sensitive to oxidative damage. Recent studies indicate that, a wide range of residue modifications can occur including formation of peroxides, 27,28 and carbonyls. Thus, the oxidative damage to tissue results in the increased amount of oxidized protein.
A detailed review by Cooke et al. provides important informations on the oxidative DNA damage, mechanisms, mutations, and related diseases. Low levels of antioxidants have been associated with the heart disease and cancer.
The other disorders to which antioxidants provide protection are cataract, cerebral ischemia, diabetes mellitus, eczema, gastrointestinal inflammatory diseases, genetic disorders. GSHPx convert the H 2 O 2 into the water Table 2. The enzyme GSHPx has strong activity towards both H 2 O 2 and fatty acid hydroperoxides eqn The different expression profiles, subcellular locations, and substrates of the antioxidant enzymes reveal the complex nature of the ROS biology.
Clearly, the antioxidant enzymes play a major role in the prevention of oxidative damage. The enzymatic antioxidants and their mechanism of antioxidant activity has been explained in details in several review articles.
The nonenzymatic antioxidants are of two types, the natural antioxidants and the synthetic antioxidants. However, the scope of this article is limited to the natural antioxidants; hence the synthetic antioxidants will not be considered for the discussion.
It functions to intercept lipid peroxyl radicals LOO˙ and to terminate the lipid peroxidation chain reactions eqn The resultant tocopheroxyl radical is relatively stable and in normal circumstances, insufficiently reactive to initiate lipid peroxidation itself, which is an essential criterion of a good antioxidant.
However, vitamin E is not an efficient scavenger of ˙OH and alkoxyl radicals ˙OR in vivo. Vitamin C or ascorbic acid 2 , is a water-soluble free radical scavenger.
Moreover, it regenerates vitamin E in cell membranes in combination with GSH or compounds capable of donating reducing equivalents. The pairs of ascorbate radicals react rapidly to produce one molecule of ascorbate and one molecule of dehydroascorbate.
The dehydroascorbate does not have any antioxidant capacity. Hence, dehydroascorbate is converted back into the ascorbate by the addition of two electrons.
The last stage of the addition of two electrons to the dehydroascorbate has been proposed to be carried out by oxidoreductase. Antioxidant potential of vitamin A 3 was first described by Monaghan and Schmitt, 52 who reported that vitamin A can protect lipids against rancidity.
Several reviews have appeared to outline the basic structural and metabolic characteristics of vitamin A and information about its potential as antioxidants in relation to the heart diseases. Bioflavonoids are a group of natural benzo-γ-pyran derivatives 4—23 and are found to possess strong antioxidant activities.
It has been reported that the bioflavonoids have a protective effect on the DNA damage induced by the hydroxyl radicals. The flavonoids complexed with the copper or iron prevent the generation of the ROS. Therefore, it is very important to consider the concentration of the chelating metal ions, such as copper or iron while evaluating the protective or degenerative effects of quercetin and other bioflavonoids.
Anthocynidine, a class of flavonoids are potential antioxidants and their effectiveness in the inhibition of the lipid oxidation is related to their metal ion-chelating activity Scheme 8 and free-radical scavenging activity Scheme 9.
Three structural groups are important determinants of the radical-scavenging activity of anthocynidines 18— Second, the 2,3 double bond in conjugation.
Third, the 4-oxofunction in the C-ring. Flavonoids form complexes with the metal ions by using the 3- or 5-hydroxyl and 4-ketosubstituents or hydroxyl groups in ortho position in the B-ring.
As shown in the Scheme 9 , the anthocynidins cynidin 19 can donate an electron accompanied by a hydrogen nucleus to a free radical from —OH groups attached to the phenolic rings.
In this process, the polyphenolic reducing agent changes to an aroxyl radical, which is comparatively more stable due to resonance than the free radical that it has reduced. The overall result is the termination of damaging oxidative chain reactions.
Carotenoids are among the most common lipid soluble phytonutrients. Lycopene 24 and β-carotene 25 are the prominent carotenoids among other different compounds. Carotenoids are well known to scavenge the peroxyl radicals more efficiently as compared to any other ROS. The peroxyl radicals generated in the process of lipid peroxidation can damage the lipids in the cell wall.
Scavenging of peroxyl radicals can disrupt the reaction sequence and prevent the damage to cellular lipids. The long unsaturated alkyl chains in carotenoids make them highly lipophilic. Carotenoids are known to play an important role in the protection of cellular membranes and lipoproteins against the ROS due to their peroxyl radical scavenging activity.
Lycopene 24 , is the most potent antioxidant naturally present in many fruits and vegetables. The high number of conjugated double bonds in lycopen endows it the singlet oxygen quenching ability. Lycopene demonstrate the strong singlet oxygen quenching ability as compared to the α-tocopherol 1 or β-carotene It is widely accepted that, the dietary antioxidants that protect LDL from oxidation can prevent the atherosclerosis and coronary heart disease.
Hydroxycinnamic acids 30—33 and their conjugates prevent oxidative damage to the LDL. The presence of the o -dihydroxy group in the phenolic ring as in caffeic acid enhances the antioxidant activity of hydroxycinnamic acids toward human LDL oxidation in vitro.
The o -dihydroxy substituents also allow the metal ion chelation similar to that of flavanoids. Theaflavin 34 and theaflavingallate 35 possesses in vitro antioxidative properties against lipid peroxidation in the erythrocyte membranes and microsomes.
They also suppress the mutagenic effects induced by H 2 O 2. Apart from the aromatic hydroxyl groups of theaflavins, the gallic acid moiety is essential for their antioxidant activity.
The theaflavingallate 35 is a stronger antioxidant than that of theaflavin Moreover, the digallate derivatives of theaflavin demonstrate the increased antioxidant activity. Allicin diallyl thiosulfinate 36 is the biologically active compound mainly found in the garlic extracts. Allicin is known to possess various biological activities including the antibacterial, antifungal, and inhibition of cancer promotion.
The S—S bond in the thiosulfinate is much weaker than the S—C bond in a sulfoxide. Hence, this process can occur at room temperature. Jump to main content. Jump to site search. You do not have JavaScript enabled.
Please enable JavaScript to access the full features of the site or access our non-JavaScript page. Issue 35, From the journal: RSC Advances. Free radicals, natural antioxidants, and their reaction mechanisms.
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Antioxidany for the inconvenience: we are taking measures to prevent Low calorie intake form Heart-healthy superfood supplement by extractors mechansms page crawlers. Received: November 27, Published: February 21, Citation: Adwas AA, Elsayed ASI, Azab AE, et al. Oxidative stress and antioxidant mechanisms in human body. J Appl Biotechnol Bioeng. DOI: Download PDF. Thank you for visiting Antioxidant mechanisms. Antioxudant are using Heart-healthy superfood supplement Energy efficiency tips version with limited support for Antiosidant. To obtain the best experience, we recommend Antioxidantt Antioxidant mechanisms a mfchanisms up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Several different reactive oxygen species ROS are generated in vivo. They have roles in the development of certain human diseases whilst also performing physiological functions.
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