Vitamin tocopheroxyl radical

Another approach to safer stabilization is to use a biological antioxidant such as vitamin E (a-tocopherol is the active form of vitamin E, AO-9, Table la). It is essentially a hindered phenol which acts as an effective chain breaking donor antioxidant, donating a hydrogen to ROO to yield a very stable tocopheroxyl radical, a-Tocopherol is a very effective melt stabilizer in polyolefins that offers high protection to the polymer at very low concentration [41], (Table 2). 

The main function of vitamin E is as a chain-breaking, free radical trapping antioxidant in cell membranes and plasma lipoproteins. It reacts with the lipid peroxide radicals formed by peroxidation of polyunsaturated fatty acids before they can establish a chain reaction. The tocopheroxyl free radical product is relatively unreactive and ultimately forms nonradical compounds. Commonly, the tocopheroxyl radical is... 

The occurrence of a 5a-C-centered tocopherol-derived radical 10, often called chromanol methide radical or chromanol methyl radical, had been postulated in literature dating back to the early days of vitamin E research,12 19 which have been cited or supposedly reconfirmed later (Fig. 6.5).8,20-22 In some accounts, radical structure 10 has been described in the literature as being a resonance form (canonic structure) of the tocopheroxyl radical, which of course is inaccurate. If indeed existing, radical 10 represents a tautomer of tocopheroxyl radical 2, being formed by achemical reaction, namely, a 1,4-shift of one 5a-proton to the 6-oxygen, but not just by a shift of electrons as in the case of resonance structures (Fig. 6.5). In all accounts mentioning... 

The last reaction commonly evoked to support the involvement of radical species 10 in tocopherol chemistry is the disproportionation of two molecules into the phenol a-tocopherol and the ort/zo-quinone methide 3 (Fig. 6.8), the latter immediately dimerizing into spiro dimer 9. This dimerization is actually a hetero-Diels-Alder process with inverse electron demand. It is largely favored, which is also reflected by the fact that spiro dimer 9 is an almost ubiquitous product and byproduct in vitamin E chemistry.28,29 The disproportionation mechanism was proposed to account for the fact that in reactions of tocopheroxyl radical 2 generated without chemical coreactants, that is, by irradiation, the spiro dimer 9 was the only major product found. 

M. Mukai, M. Nishimura, K. Ishizu, and Y. Kitamura, Kinetic study of the reaction of vitamin C with vitamin E radicals (tocopheroxyls) in solution, Biochim. Biophys. Acta, 991 (1989) 276-279. 

Similarly, the antioxidant activity of vitamin E is centreed on its chainbreaking donor activity in-vitro rate studies on a-tocopherol have shown that it is one of the most efficient alkylperoxyl radical traps, far better than commercial hindered phenols such as BHT, 2,6-di- ferf.butyl-4-methylphe-nol. Its efficiency was attributed [30, 31] to the highly stabilised structure of tocopheroxyl radical (which is formed during the rate-limiting step, reaction 3) because of favourable overlap between the p-orbitals on the two oxygen atoms. 

FIGURE 29.1 Pathways of the chain-breaking action of vitamin E in lipid peroxidation and its subsequent regeneration. LOOH lipid hydroperoxide, LOO lipid peroxyl radical, vitamin C ascorbate radical (semi-dehydroascorbate), vitamin E a-tocopheroxyl radical. The lipid peroxyl radical is reduced to lipid hydroperoxide by tocopherol. The resulting tocopheroxyl radical can be re-reduced by ascorbate. The thus formed ascorbate radical can be reduced to ascorbate by the NADH-dependent semidehydroascorbate reductase. 

The rate constant for the bimolecular decay of the a-tocopheroxyl radical is only 3.5x 102M-1 s . Therefore, its half-life is several hours in chloroform at ambient temperature. This implies that vitamin E free radical can react with a second peroxyl radical. In biological membranes, a-tocopherylquinone is generally believed to be the major end-product, but the mechanism of its production remains controversial. It may arise either from the decomposition of a-tocopherone, or from dismutation of a-tocopheroxyl radicals. However, the steady-state concentration of a-tocopherylquinone is usually too low to be measurable ex vivo when tissue homogenization and extraction are performed in the presence of pyrogallol and butylated hydroxytoluene, respectively,... 

Reduction of the Vitamin E Radical by Ascorbate Asdiscussed in Section 4.3.1, one of the major roles of vitamin E is as a radical-trapping antioxidant in membranes and lipoproteins. a-Tocopherol reacts with lipid peroxides forming the a-tocopheroxyl radical, which reacts with ascorbate in the aqueous phase, regenerating a-tocopherol, and forming monodehydroascorbate. Vitamin C may have a vitamin E-sparing antioxidant action, coupling lipophilic and hydrophilic reactions. 

In contrast with all the described antioxidant properties of vitamin E, it has been shown that lipid peroxidation of LDL is faster in the presence a-tocopherol, and is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or in vivo [10, 11]. It was thus proposed that peroxidation is propagated within lipoprotein particles by the vitamin E radical i.e. a-tocopheroxyl radical) unless it became reduced by vitamin C or ubiquinol-10 [12]. However, the importance of pro-oxidation reactions of a-tocopherol in vivo, under physiological conditions, appears to be questionable. 

Liebler, D., and Burr, J. (1992). Oxidation of vitamin E during iron-catalyzed lipid peroxidation Evidence for electron-transfer reactions of the tocopheroxyl radical. Biochemistry 31, 8278-8284. 

Ascorbate protects membranes through two mechanisms. First, ascorbate reacts with peroxyl radicals formed in the cytoplasm before they can reach the membrane, thereby preventing lipid peroxidation. Second, ascorbate enhances the antioxidant activity of vitamin E by regenerating reduced a-tocopherol from the a-tocopheroxyl radical (Figure 10.23). Ascorbate is then regenerated by reacting with GSH. 

Such ascorbate free radicals are important intermediates in a wide variety of in vitro reactions involving oxidation and reduction and there is evidence that ascorbate radicals also have an important role in living systems. Vitamin C is known to interact with the tocopheroxyl radical... 

Coenzyme Q (Q) in its reduced form (ubiquinol) is known to inhibit LPO in subcellular membranes (Mellors and Tappel, 1966 Forsmak et al., 1991), either by reducing the a-tocopheroxyl radical (TO) back to a-tocopherol (TOH) (Kagan et al., 1990) or by reacting directly with radicals. However, by far the most information exists, to date, for vitamin E and vitamin C (ascorbate). 

In vitro studies strongly support the theory that the antioxidant effect of ascorbate is related to the direct regeneration of vitamin E by reducing the tocopheroxyl radical in a one-electron redox cycle [Eq. (2) Sharma and Buettner, 1993]. 

However, the possibility that ascorbate prevents oxidation of vitamin E by reducing oxidated lipid substrates and not the tocopheroxyl radical cannot be excluded. Furthermore, in vivo studies do not show a clear correlation between ascorbate status and rates of a-tocopherol turnover (Liebler, 1993). 

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