Reduction of the Vitamin E Radical by Ascorbate

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. 

Antioxidant activity involving the transfer of two electrons between the ascorbate/dehy-droascorbate redox couple or donation of one electron to inactivate highly reactive free radicals, e.g., protection of vitamin E by reduction of the tocopheryl radical Competitive inhibition in substrate binding reactions, including inhibition of the formation of carcinogenic nitrosamines... 

Already three decades ago, it was proposed by Tappel (45) that a synergy between Vitamin E and ascorbic acid existed (46), as the reduction potential of the ascorbate radical/ascorbate system at pH 7.0 is 0.28 V, vdiich is above that of the a-tocopherol radical/a-tocopherol (E = 0.5) (47) a-Toc + AscH" —> a-TocH + Asc ... 

The discovery and characterization of the thiyl/thiolate conjugation equilibrium (3) [14] is one of the most significant contributions of the pulse radiolysis technique to the chemistry of cellular oxidative stress. Without such measurements, including the direct observation of the reduction of thiyl radicals by ascorbate [13] and electron transfer from disulphide radical anions to oxygen [ 15], it would be indeed difficult to prepare a reasoned argument for the competing reaction pathways from a quantitative viewpoint. Further work is needed to develop these concepts further. Not least, the dimension of space (as well as an appreciation of interfacial phenomena) needs to be added to the dimension of time if we are to model realistically the cellular environment and assess quantitatively, for example, the importance of the synergy between the lipophilic phenolic antioxidant, vitamin E and the hydrophilic electron-donor, vitamin C (ascorbate) [134]. 

The antioxidants studied can be classified into two broad types phenolic antioxidants and non-phenolic antioxidants. Phenolic antioxidants have been found to be more promising as they are obtained from dietary sources.Vitamin E (a-tocopherol), the first known chainbreaking antioxidant, is also an o-methoxy phenol. Pulse radiolysis studies of vitamin E and its water-soluble analogue, trolox C, have been reported several years ago. a-tocopherol reacts with almost all the oxidizing free radicals, and the phenoxyl radicals produced during oxidation reactions absorb at -460 nm (Fig. 1). The regeneration reaction of a-tocopherol phenoxyl radicals back to a-tocopherol by water-soluble antioxidant ascorbic acid was also first reported by pulse radiolysis method. The one-electron reduction potential of vitamin E is -0.48 V vs. NHE. Both a-tocopherol and trolox C are used as standards for evaluating the antioxidant ability of new compounds. 

Low molecular weight antioxidants react with ROS in cell compartments which for some reasons are lack of antioxidant enzymes. Thus, suppression of bifurcate chain reactions of lipid peroxidation in hydrophobic core of cell membrane is mostly effectively performed by vitamin E (a-tocopherol). Interaction of lipid molecules with hydroxyl radical in the absence of vitamin E results in bifurcation of oxidative processes and formation of peroxyl and alcoxyl radicals. They are quickly accumulated in the restricted volume of the membrane and reaction began to be uncontrolled. a-Tocopherol interacts with peroxyl radicals with high affinity, reduces them and is then oxidized itself into relatively nonactive phenoxyl radical [8]. The latter can be accumulated within the bilayer until it will be returned to initial state by reduction by ascorbate [9]. Pair Vitamin E - Vitamin C is a good example of a mutual interaction between hydrophobic and hydrophilic low molecular weight antioxidants. Recently, tight relations were demonstrated for several natural antioxidants which interaction balances the red/ox state of the cell [3.5.10-12]. Figure 4 demonstrates such interaction between some of them. 

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