Antioxidant Functions of Vitamin

Vitamin E functions as a lipid antioxidant hoth in vitro and in vivo a numher of synthetic antioxidants will prevent or cure most of the signs of vitamin E deficiency in experimental animals. Polyunsaturated fatty acids undergo oxidative attack by hydroxyl radicals and superoxide to yield alkylperoxyl (alkyl-dioxyl) radicals, whichperpetuate a chain reactionin the lipid-withpotentially disastrous consequences for cells. Similar oxidative radical damage can occur to proteins (especially in a lipid environment) and nucleic acids. 

Phenolic compounds can break such chain reactions hy trapping the radicals, with the formation of stable nonradical products from the oxidized lipid and phenoxyl radicals that are relatively unreactive because they are stabilized by resonance. The phenoxyl radical may either react with a further alkylperoxyl radical to yield nonradical products, or it may be reduced back to the starting phenol by reaction with a water-soluble reducing agent. 

Tocopherol can act catalyticaUy as a chain-breaking lipophilic antioxidant in membranes and plasma lipoproteins, because the tocopheroxyl radical formed by reaction of a-tocopherol with a lipid peroxide radical can be reduced to tocopherol in four main ways  

By reaction with ascorbate to yield the monodehydroascorbate radical, which in turn can either be reduced to ascorbate or can undergo dis-mutation to yield dehydroascorbate and ascorbate (Section 13.4.7.1). In vitro, the formation of the tocopheroxyl radical can be demonstrated by the appearance of its characteristic absorbance peak, which normally has a decay time of 3 msec in the presence of ascorbate, the tocopheroxyl peak has a decay time of 10 /rsec, and its disappearance is accompanied by the appearance of the monodehydroascorbate peak. There is an integral membrane oxidoreductase that uses ascorbate as the preferred electron donor, linked either directly to reduction of tocopheroxyl radical or via an electron transport chain involving ubiquinone (see no. 4 below May, 1999). 

By reaction with glutathione, catalyzed by a membrane-specific isoenzyme of glutathione peroxidase, which is a selenoenzyme. Thus, in 

By reaction with other lipid-soluble antioxidants in the membrane or lipoprotein, including ubiquinone (Section 14.6), wbicb is present in Ituge amounts in all membranes as part of an electron transport cbcdn, not just tbe mitocbondrial inner membrane (Thomas et al., 1995 Crtme tmd Navas, 1997 Tbomas and Stocker, 2000 Villalba and Navcis, 2000). 

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Vitamin E is widespread in foods and is stored in the body so that deficiency states are very rare. A possible exception may be premature infants with very low fat stores. The concentration of a-tocopherol in cows milk ranges from 3.0 to 5.0 mg/L and is present at about the same level in human milk. While vitamin E has been shown to be essential for normal fertility in rats and other animals, it has never been proven to be necessary for human fertility. However, in recent years there has been renewed interest in the antioxidant function of vitamin E [e.g., in protecting the cardiovascular system (Sytkowski et al., 1990 Gurr, 1994)]. 

V. Kagan and L. Packer, Antioxidative function of vitamin E and ubiquinols. Meth. Toxicol., 2,... 

Liebler, D. C., 1993, The role of metabolism in antioxidant functions of vitamin E, Crit. Rev. Toxicol. 23 147-169. 

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... 

Vitamin C occurs as L-ascorbic acid and dihydroascorbic acid in fruits, vegetables and potatoes, as well as in processed foods to which it has been added as an antioxidant. The only wholly undisputed function of vitamin C is the prevention of scurvy. Although this is the physiological rationale for the currently recommended intake levels, there is growing evidence that vitamin C may provide additional protective effects against other diseases including cancer, and the recommended dietary allowance (RDA) may be increased in the near future. Scurvy develops in adults whose habitual intake of vitamin C falls below 1 mg/d, and under experimental conditions 10 mg/d is sufficient to prevent or alleviate symptoms (Bartley et al., 1953). The RDA is 60 mg per day in the USA, but plasma levels of ascorbate do not achieve saturation until daily intakes reach around 100 mg (Bates et al., 1979). Most of the ascorbate in human diets is derived from natural sources, and consumers who eat five portions, or about 400-500 g, of fruits and vegetables per day could obtain as much as 200 mg of ascorbate. 

Huge literature on biological functions of flavonoids and their antioxidant and free radical scavenging activities successfully competes with work on antioxidant effects of vitamins E and C. Flavonoids have been reported to exert multiple biological effects and exhibit antiinflammatory, antiallergic, antiviral, and anticancer activities [85 89], However, considering flavonoids as the inhibitors of free radical-mediated processes, two types of their reactions should be discussed flavonoids as free radical scavengers (antioxidants) and flavonoids as metal chelators. 

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. 

The E vitamins consist of eight naturally occurring tocopherols, of which a-tocopherol is the most active (Figure 28.28). The primary function of vitamin E is as an antioxidant in prevention of the nonenzymic oxidation of cell components (for example, polyunsaturated fatty acids) by molec ular oxygen and free radicals. 

It has been known for some time that vitamin E can act as an antioxidant within the body [21, 61] and that the biological potency of the tocopherols is proportional to their antioxidant activity [62], Synthetic antioxidants, which often have structures unrelated to that of the vitamin, are also capable of preventing the symptoms of vitamin E deficiency [23, 24, 63, 64]. The general proposal [63, 65], therefore, is that the function of vitamin E is one of an in vivo antioxidant, protecting membrane phospholipids from attack by free radicals generated within the cell. 

Thought to function as antioxidants and also to enhance the antioxidant effects of vitamin C... 

For a long time, it was considered that, unlike the other vitamins, vitamin E had no specific functions rather it was the major Upid-soluble, radicaltrapping antioxidant in membranes. Many of its functions can be met by synthetic antioxidants however, some of the effects of vitamin E deficiency in experimental animals, including testicular atrophy and necrotizing myopathy, do not respond to synthetic antioxidants. The antioxidant roles of vitamin E and the trace element selenium are closely related and, to a great extent, either can compensate for a deficiency of the other. The sulfur amino acids (methionine and cysteine) also have a vitamin E-sparing effect. 

The best-established function of vitamin E is as a lipid-soluble antioxidant in plasma lipoproteins and cell membranes. Many of the antioxidant actions are unspecific, and a number of synthetic antioxidants have a vitamin E-sparing effect. There is considerable overlap between the antioxidant roles of vitamin E and selenium (Section 4.3.2). 

The amount of vitamin C sufficient to alleviate and cure the clinical signs of scurvy is only lOmg/day, which is probably near the minimum requirement in man. This amount, however, is not adequate to maintain near saturation of tissue in the adult human male, who has a body pool of 1.5 to 2 g and shows chnical symptoms of deficiency when this total pool falls below about 300 mg. Acknowledgment of functions of vitamin C beyond the antiscorbutic, particularly the antioxidant function, has led to the development of the concept of the optimal nutrition state, and the intake... 

The ene-diol function is essential to the antioxidant properties of vitamin C, it is therefore not surprising that its methylation leads to an inactive compound (Figure 20.9). 

Vitamin C traps radicals formed in aqueous environments (Section 9.8). It is an antioxidant because it prevents oxidation reactions by radicals. Not all the physiological functions of vitamin C are known. What is known, though, is that vitamin C is required for the synthesis of collagen, which is the structural protein of skin, tendons, connective tissue, and bone. If vitamin C is not present in the diet (it is abundant in citrus fruits and tomatoes), lesions appear on... 

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