Tocopherols vitamin free radicals

Figure 45-6. Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) of the cell and the aqueous phase (cytosol). (R-,free radical PUFA-00-, peroxyl free radical of polyunsaturated fatty acid in membrane phospholipid PUFA-OOH, hydroperoxy polyunsaturated fatty acid in membrane phospholipid released as hydroperoxy free fatty acid into cytosol by the action of phospholipase Aj PUFA-OH, hydroxy polyunsaturated fatty acid TocOH, vitamin E (a-tocopherol) TocO, free radical of a-tocopherol Se, selenium GSH, reduced glutathione GS-SG, oxidized glutathione, which is returned to the reduced state after reaction with NADPH catalyzed by glutathione reductase PUFA-H, polyunsaturated fatty acid.)...

Fig 24.18. Vitamin E (a-tocopherol) terminates free radical hpid peroxidation by donating single electrons to hpid peroxyl radicals (LOO ) to form the more stable lipid pieroxide, LOOK. In so doing, the a-tocopherol is converted to the fully oxidized tocopheryl quinone. 

Vitamin E actually consists of a family of compounds, the most active of which is a-tocopherol. The mechanism of the vitamin s action is not completely certain, but it seems likely that it might undergo hydrogen atom transfer reactions with free radicals to give a stable radical (see also Chapter 17, Problem 7). 

In 1922, Evans and Bishop named the animal nutritional factor essential of reproduction Vitamin E . In the 1960s, vitamin E was associated with antioxidant function. Twenty-five years later, vitamin E has been found to possess functions that are independent of its antioxidant and free radical scavenging ability. a-Tocopherol specific molecular mechanisms were discovered which are still under investigation. 

Vitamin E (tocopherol) is the most important antioxidant in the body, acting in the lipid phase of membranes and protecting against the effects of free radicals. Vitamin K functions as cofactor to a carboxylase that acts on glutamate residues of clotting factor precursor proteins to enable them to chelate calcium. 

Antioxidants Reducing agents, such as vitamins C (ascorbic acid) and E (a-tocopherol), which scavenge toxic free radicals generated by oxidative reactions in the cell. 

The efficiency of vitamin E in the suppression of free radical-mediated damage induced by iron overload has been studied in animals and humans. Galleano and Puntarulo [46] showed that iron overload increased lipid and protein peroxidation in rat liver. Vitamin E supplementation successfully suppressed these effects and led to an increase in a-tocopherol, ubiquinone-9, and ubiquinone-10 contents in liver. Important results were obtained by Roob et al. [47] who found that vitamin E supplementation attenuated lipid peroxidation (measured as plasma MDA and plasma lipid peroxides) in patients on hemodialysis after receiving iron hydroxide sucrose complex intravenously during hemodialysis session. These findings support the proposal that iron overload enhances free radical-mediated damage in humans. 

Both vitamin E and vitamin C are able to react with peroxynitrite and suppress its toxic effects in biological systems. For example, it has been shown [83] that peroxynitrite efficiently oxidized both mitochondrial and synaptosomal a-tocopherol. Ascorbate protected against peroxynitrite-induced oxidation reactions by the interaction with free radicals formed in these reactions [84]. 

Another fat-soluble vitamin, E, was found by Evans and Bishop in 1923. Pregnant rats on a defined diet (alcohol-extracted casein, cornstarch, and lard) supplemented with butter (vitamins A and D) and yeast extract (vitamin B group) produced few young because of fetal resorption. Male rats on the same diet were sterile. The disorders, which have not been identified in man, were corrected by wheat-germ oil, from which tocopherol, the active ingredient, was isolated in 1936. In spite of intensive investigations and a recognition that the vitamin is an antioxidant and destroyer of free radicals, the function of vitamin E remains obscure. 

Biological antioxidants such as a-tocopherol (65, vitamin E) serve to inhibit free radical chain oxidation, and the mechanisms of their reactions have attracted close attention. The chain-breaking reaction of such phenols with peroxyl radicals is by hydrogen transfer (equation 101). 

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