Vitamins E and

Methyl groups of the aromatic ring of vitamins E and K have been replaced by trifluoromethyl. Replacement of the three methyls of the side chain by one or several trifluoromethyls (Wittig-Uke approach from ad hoc trifluoromethyl ketones) as well as the difluorination at CA (synthesized from bromodifluoroacetate) in vitamin E (tocopherol) have also been realized (Eigure 4.28). The relaxation times T2 of the various CF3 groups have been measured in suspensions of hposomic bilayers and compared to those obtained in solution. The goal of these studies was to determine the mobility and the molecular orientation of the vitamin in a lipidic bilayer. 

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Infants maybe sensitive to doses of vitamin A [11103-57-4] in the range of 75,000—200,000 lU (22.5—60 mg), although the toxic dose in adults is probably 2—5 million lU (90.6—1.5 g). Intakes in this range from normal food suppHes without oral supplements are simply beyond imagination (79). Vitamin D [1406-16-2] toxicity is much more difficult to substantiate clinically. Humans can synthesize active forms of the vitamin in the skin upon irradiation of 7-dehydrocholesterol. Toxic symptoms are relatively nonspecific, and dangerous doses seem to He in the range of 1000—3000 lU/kg body wt (25—75 flg/kg body wt) (80). Cases of toxicity of both vitamins E and K have been reported, but under ordinary circumstances these vitamins are considered relatively innocuous (81). 

Phytol [505-06-5] (111) and isophytol [150-86-7] (112) are important intermediates used in commercial synthesis of Vitamins E and K. There is a variety of synthetic methods for their manufacture. Chlorophyll [479-61-8] is a phytyl ester. 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Thus, it is uncertain to what extent the apparent protective effects of fruit and vegetable consumption on risk of stomach cancer can be attributable to their phytoestrogen content. This appears not to have been studied directly, and other constituents such as ascorbic acid (vitamin C), a-tocopherol (vitamin E) and /1-carotene may be potentially protective. 

Heinecke JW (2001) Is the emperor wearing clothes Clinical trials of vitamin E and the LDL oxidation hypothesis. Arterioscler Thromb Vase Biol 21 1261—1264... 

One excellent UV protector for foods is PABA, a B vitamin. Likewise, many of the same antioxidants we ingest as health supplements—such as vitamin C and a similar chemical, erythorbic acid vitamin E and lecithin, a source of the important nutrients choline and inositol—occur naturally in food. 

Besides other functions, vitamin Bj2 and fohc acid take part in providing one-carbon residues for DNA synthesis, deficiency resulting in megaloblastic anemia. Vitamin C is a water-soluble antioxidant that maintains vitamin E and many metal cofactors in the reduced state. 

ALPHA-TOCOPHEROL BETA-CAROTENE (ATBC) CANCER PREVENTION STUDY GROUP (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers , New Engl J Med, 330, 1029. 

Natural antioxidants may be classified according to their nutritive value or according to their solubility. The hydrophobic vitamin E and the hydrophilic vitamin C are thus important both as nutrients and as antioxidants. The nonnutritive antioxidants may similarly be divided into lipid-soluble and water-soluble antioxidants, as shown in Fig. 16.3, which will also form the basis for a discussion of exploitation of combinations of anhoxidants in order to improve protective effects. 

NIKI E, SAITO T, KAWAKAMI A and KAMIYA Y (1984) Inhibition of oxidation of methyl linoleate by vitamin E and vitamin C, J Biol Chem, 259, 4177-82. 

VALGiMiGLi L, BANKS J T, INGOLD K u and LuszTYK J (1995) Kiuetic solveut effects on hydroxylic hydrogen atom abstractions are independent of the nature of the abstrarting radical. Two extreme tests using vitamin E and phenol, J Am Chem Soc, 117, 9966-71. 

Squalene is an isoprenoid compound that is found in large quantities in shark liver and in smaller quantities in olives, rice bran and wheat germ. It is a bactericidal compound and an antioxidant and it aids in skin nutrition. Several cosmetic applications of rice bran and rice bran oil arise from the biological effects of their squalene, vitamin E and y-oryzanol content. Since these compounds are fat-soluble, rice bran oil is used for all these preparations. 

Nonaqueous Systems In nonaqueous (nonpolar) solvent systems, nitrosatlon also proceeds. In these solvents, alpha-tocopherol acts as a lipid soluble blocking agent in much the same fashion as ascorbic acid functions in the aqueous phase. Alpha-tocopherol reacts with a nitrosating agent and reduces it to nitric oxide. At the same time, alpha-tocopherol is oxidized to tocoquinone, which is the first oxidation product of vitamin E and also a normal metabolite in vivo. 

Sato, K., Niki, E. and Shimasaki, H. (1990). Free radical mediated chain oxidation of LDL and its synergistic inhibition by vitamin E and vitamin C. Arch. Biochem. Biophys. 279, 402-405. 

Gey, K.F., Puska, J.M., Jordan, P. and Moser, U.K. (1991). Inverse correlation between plasma vitamin E and mortality from ischaemic heart disease in cross-cultural epidemiology. Am. J. CUn. Nutr. 53, 3265-3345. 

Packer, J.E., Slater, T.F. and Willson, R.L. (1979). Direct observation of a fiee radical reaction between vitamin E and vitamin C. Nature 278, 737-738. 

The free-radical defence mechanisms utilized by the brain are similar to those found in other tissues. The enzymes SOD, catalase, glutathione peroxidase, and the typical radical scavengers, ascorbate, vitamin E and vitamin A are present in the brain, as they are in peripheral tissues. However, the brain may actually be slightly deficient in some of these defence mechanisms when compared to the amounts present in other tissues. 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Tripathi, B. and Tripathi, R. (1984). Cellular and subcellular events in retinopathy of oxygen toxicity with a preliminary report on the preventative role of vitamin E and gamma-aminobutyric acid a study in vitro. Curr. Eye Res. 3, 193-208. 

Empey, L.R., Papp, J.D., Jewell, L.D. and Fedorak, R.N. (1992). Mucosal protective effects of vitamin E and misoprostol during acute radiation-induced enteritis. Dig. Dis. Sci. 37, 205-214. 

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