Vitamin interactions with /-tocopherol

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.)...

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

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]. 

The absorption of vitamin E is relatively poor - only some 20% to 40% of a test dose is normally absorbed from the small intestine, in mixed lipid micelles with other dietary lipids. This absorption is enhanced by medium-chain triglycerides and inhibited by polyunsaturated fatty acids, possibly because of chemical interactions between tocopherols and polyunsaturated fatty acids or their peroxidation products in the intestinal lumen. Esters are hydrolyzed in the intestinal lumen hy pancreatic esterase and also by intracellular esterases in the mucosal cells. 

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. 

The vitamins E and C are interrelated in their antioxidant capabilities. Active a-tocopherol can be regenerated by interaction with vitamin C following scavenge of a peroxy free radical. Alternatively, a-tocopherol can scavenge two peroxy free radicals and then be conjugated to glucuronate for excretion in the bile. 

Vitamin E stabilizes erythrocytes against lysis initiated by vitamin A vitro (Lucy and Dingle, 1964) and vivo (Soliman, 1972). Other reports demonstrated the conservation of hepatic stores of vitamin A by vitamin E (Davies and Moore, 1941) and confirmed by Cawthorne et al (1968). However, utilizations of 3-carotene in the presence of high intakes of tocopherol were blocked (Arnrich, 1978). The latter study suggested that tocopherol interacts with 3 carotene in the biochemical steps that occur just before the formation of retinol. 

Recent studies indicate that a-tocopherol can also directly react with alkyl macroradicals, this reaction being more likely due to the higher mobility of the alkyl macroradicals compared to that of peroxy radicals [70]. The alkyl macroradicals react with a-tocopherol, giving a polymeric saturated molecule and a stabilized phenoxy radical (Scheme 13, Part B). The phenoxy radical can in turn interact with another alkyl macroradical leading to the formation of a,(3-unsaturated ketones [69, 70]. This mechanism indicates a double efficiency of stabiUzation of vitamin E one vitamin E molecule can convert up to two alkyl macroradicals to umeactive species. 

Vitamin E deficiency occurs only rarely in humans and almost never as a result of inadequate vitamin E intakes, therefore, interactions with other nutrients have not been well studied. There have been reports of vitamin E deficiency symptoms in persons with protein-calorie malnutrition. Vitamin E deficiency does occur as a result of genetic abnormalities in a-TTP and as a result of various fat malabsorption syndromes. Vitamin E supplementation halts the progression of the neurologic abnormalities caused by inadequate nerve tissue a-tocopherol and, in some cases, has reversed them. 

Urano, S. etal., Membrane stabilization of vitamin E interactions of alpha-tocopherol with phospholipids in bilayer liposomes, Biochem. Biophys. Res. Commun., 146, 1413, 1987. 

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