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Mechanisms and Biomarkers (WG 4) page 15<br />

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radicals including N-acetylcysteine acting through elevation of intracellular cysteine (hence<br />

glutathione) and homocysteine which can be involved in the control of the plasma redox thiol<br />

status (Brooks et al., 1991).<br />

Ubiquinone (Coenzyme Q10): this powerful antioxidant is a fat soluble quinone mainly found<br />

in the inner membrane of mitochondria. Its level in mitochondrial membrane is 10 times<br />

higher than in plasma membrane when compared with another lipid soluble antioxidant such<br />

as vitamin E (Takada et al., 1982). It is as efficient as vitamin E in chain-breaking antioxidant<br />

reactions. However, it is believed to regenerate vitamin E radical (tocopheroxyl) formed while<br />

preventing lipid peroxidation (Frei et al., 1990). The oxidised product of ubiquinone<br />

(ubisemiquinone) is reduced back by the electron transport chain of mitochondrial respiratory<br />

chain.<br />

Vitamin E provided by the food is a fat soluble antioxidant found in all lipid structures<br />

(membranes and HDL/LDL). The plasma level is about 15 µg/mL and up to 7 molecules of<br />

vitamin E was found per molecule of LDL (Esterbauer et al., 1989). Vitamin E comprises 8<br />

naturally occurring homologues defined as tocopherols. The most abundant α-tocopherol is a<br />

chain breaking agent reacting with lipid oxides and preventing lipid peroxidation (Diplock et<br />

al., 1989). Such a reaction leads to the formation of tocopheroxyl radical which, by spreading<br />

the energy of the unpaired electron into the entire structure, increases the half life of the<br />

radical and hence blocks the reactivity of the captured electron. Tocopheroxyl can react either<br />

with another tocopheroxyl or lipid peroxide radical to form stable vitamin E dimer and<br />

vitamin E-lipid adduct respectively. The tocopheroxyl radical can also be regenerated to<br />

tocopherol either by ubiquinone from inner mitochondrial membrane or by vitamin C from<br />

the aqueous compartment of cell cytoplasm (Kagan et al., 1990). This latter reaction is an<br />

important way to maintain the level of α-tocopherol in the membrane at the expense of<br />

vitamin C.<br />

Vitamin C (or ascorbic acid) is a water soluble compound found at relatively low<br />

concentration in the plasma (40-140 µmol/L) and can attain millimolar level in tissues. It is<br />

essential for humans as it cannot be synthesised and is obtained from the diet (and/or<br />

supplement). Besides of several important metabolic roles, ascorbate also has the capacity to<br />

scavenge in vivo almost all reactive oxygen and nitrogen radical species (Rose and Bode,<br />

1993). Its antioxidant property results from the formation of semidehydroascorbate which is<br />

less reactive than the free radicals scavenged (Bendish et al., 1986). As discussed above, one<br />

of the roles of vitamin C is to act synergistically with vitamin E through the reduction of α-

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