Vitamin E radical

Compare the spin density surface for vitamin E radical to those of phenoxy and BHT radicals (see also Chapter 16, Problem 2). Are there significant differences among the three If so, elaborate. What is the function of the long alkyl chain in vitamin E Examine an electrostatic potential map for vitamin E radical. Do you expect it to be soluble in aqueous (polar) or non-aqueous (non-polar) environments, or both ... 

Thiols are also important protection against lipid peroxidation. Glutathione (7-Glu-Cys-Gly) is used by several glutathione-dependent enzymes such as free-radical reductase (converts vitamin E radical to vitamin E), glutathione peroxidase (reduces hydrogen peroxide and lipid hydroperoxides to water and to the lipid alcohol, respectively), and others. In addition, the thiol group of many proteins is essential for function. Oxidation of the thiol of calcium ATPases impairs function and leads to increased intracellular calcium. Thiol derivatives such as the ovothiols (l-methyl-4-mercaptohistidines) (Shapiro, 1991) have been explored as therapeutics. 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

Edge, R, Land, EJ, McGarvey, D, Mulroy, L, and Truscott, TG, 1998. Relative one-electron reduction potentials of carotenoid radical cations and the interactions of carotenoids with the vitamin E radical cation. J Am Chem Soc 120, 4087 1090. 

The ascorbate radical is one of the radicals that do not react readily with 02, but it reacts with 02 ". The product of this reaction is not yet known. There are other radicals that have similar properties such as phenoxyl-type radicals. A prominent member of this group is the vitamin E radical. In the phenoxyl radical series, addition as well as ET have been discussed (Jonsson et al. 1993 d Alessandro et al. 2000). The reaction of the tyrosyl radical with 02 is an example showing that addition is the main route despite of its relatively high redox potential [reactions (97)—(99) only one pathway is shown Jin et al. 1993],... 

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. 

Kagan, V. et al., Ultraviolett light-induced generation of vitamin E radicals and their recycling. A possible photosensitizing effect of vitamin E in skin, Free Radical Res. Commun., 16, 51, 1992. 

Moreover, when 02 is formed in the hydrophobic stage, vitamin E (20, tocopherol) creates a hydrogen atom. The hydrogen peroxide formed is decomposed to water and molecular oxygen catalyzed by catalase enzyme (protein containing Fe-complex), and the oxidized vitamin E radical is reduced to vitamin E again by vitamin C (eq. 1.10)... 

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. 

Bisby RH. (1990) Interaction of vitamin E radicals and membrane. Free Radical Res Com 8 299-306. 

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. 

The differing H donating potencies of various forms of vitamin E depend, in part, on how w ell the lone pair electrons car stabilize the vitamin E radical. The vitamin E radical may also be called a chromanoxyl radical. 

Vitamin E can interrupt or prevent the chain reaction. Vitamin E can ad to convert the PUFA peroxy radical to a FUFA hydroperoxide (Step 5). I his prevents the PUFA peroxy radical from inflicting damage on a neighboring PUFA. Tire vitamin, in turn, is converted to a vitamin E radical. The vitamin E radical is relatively stable and unreactive and is thought not to cause further damage to the cell membrane. 

Damage to cell membranes may be initiated by the reaction of the hydroxyl radical with a PUFA, generating a PUPA radical. The hydroxyl radical is converted to water (Figure 9.91). The PUFA radical, in turn, can be repaired by vitamin E (Figure 9.92). Involvement of vitamin E in this repair results in its conversion to a vitamin E radical. The vitamin E radical is relatively unreactive and does not cause further damage to the cell. In the absence of vitamin E, the PUFA radical may induce a chain reaction, resulting in widespread damage to cell membranes. 

Interaction Between Vitamin E- Radicals and Ascorbate. Vitamin E and ascorbate probably act synergistically (55) that is, vitamin E acts as the primary antioxidant (particularly in biomembranes) and the resulting vitamin E- radical then reacts with ascorbate to regenerate vitamin E. That such a reaction can occur was subsequently demonstrated (56), and the reaction rate (/c42 1.55 0.2 X 10 was... 

These molecules scavenge radicals and vitamin E can react with an alkoxyl radical by donating a hydrogen atom (from the OH group) to give an alcohol and a vitamin E radical, which is much less harmful. Vitamin E is believed to be regenerated by reaction with vitamin C at the cell membrane (water-lipid) surface. 

Edge, R., Land, E.J., McGarvey, D., Mulroy, L., and Truscott, T.G. (1998) Relative one-electron reduction potentials of carotenoid radical cations and the interactions of carotenoids with the vitamin E radical cation, J. Am. Chem. Soc., 120, 4087 4090. Fleschner, C.R. (1995) Fatty acid composition of triacylglycerols, free fatty acid and phospholipids from bovine lens membrane fractions, Invest. Ophthal. Vis. Sci., 36, 261-264. Fraunfelder, F.T. (1982) Drug-Induced Ocular Side Effects and Drug Interactions, 2nd ed., Philadelphia Lea Febiger. 

The interaction of carotenoids and carotenoid radicals with other anti-oxidants is of importance with respect to anti-oxidative and possibly pro-oxidative reactions of carotenoids. All the radical cations of the carotenoids studied reacted with vitamin C so as to repair the carotenoid (e.g. in methanol, CAR t AscH CAR + AscH -I- H ). hi polar environments the vitamin E radical cation is deprotonated (TOH —> TO -i- H ) and TO does not react with carotenoids, whereas in non-polar environments, TOH is converted into TOH by hydrocarbon carotenoids, hi aU solvents studied, singlet oxygen is efficiently quenched by carotenoids that have appropriate low-lying triplet energy levels O -i- CAR -> Oj -i- CAR". However, such reactions are stiU to be observed in vivo. 

Work with 1,1 dihydro-/3-carotene (7,8-dihydro-8, 7-rett2-/3,/3-carotene, 77DH) and vitamin E has allowed Edge et al. (1998) to gain a better understanding of the interaction of the vitamin E radicals with carotenoids. Figure 3 shows the transient... 

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