Pro-oxidant activity of vitamin C in drinking water ... - Ã bo Akademi

Review of the literatureAsc • is a poorly reactive radical that can be converted back to ascorbate by other, strongerreducing agents, such as NADH-dependent enzymes. 67, 68 Alternatively, Asc • can undergodisproportionation to form DHA. 5, 69, 70 The reactivity of Asc • can account for many ofascorbate’s antioxidant effects. 70, 71 DHA on the other hand is very unstable, even in theabsence of oxygen, 72 and the lactone ring of DHA can be opened and cleaved into oxalicacid and threonic acid via diketo-gulonic acid (Figure 2).Vitamin C can reduce an oxidized substrate if the substrate has a lower reduction potential.One of the most well-documented antioxidant effects of vitamin C is to regenerate otheroxidized substrates such as vitamin E. Vitamin C has been suggested to be beneficial inatherosclerosis, due to its ability to regenerate oxidized vitamin E (α-tocopherol) inmembranes and lipoproteins in vitro. 73, 74 The ability of vitamin C to regenerate oxidizedsubstrate is not only seen in vitamin E, as vitamin C has also been shown to regenerateglutathione, β-carotene and urate from their one electron oxidized form in vitro. 6, 75, 76 In thecase of vitamin E, vitamin C has the capacity to regenerate vitamin E (α-tocopherol) fromthe α-tocopheryl radical (Figure 3).O 2HO2 OHLLHLIPIDMEMBRANELOOHLOOα-TOα-TOHAscAscFigure 3. A schematic illustration of the regeneration of vitamin E (α-tocopherol) by vitamin C (ascorbate)in the aqueous/lipid inter-phase of a lipid bilayer. The illustration also shows a hydroxyl radical(OH • ) attack on a lipid (LH) forming a lipid radical (L • ). The lipid radical will thereafter forma lipid peroxyl radical (LOO • ) in the presence of oxygen (O 2 ). Vitamin E (α-tocopherol (α-TOH)) will remove the lipid peroxyl radical. Ascorbate (Asc) recycle α-tocopherol (α-TOH)from the α-tocopheryl radical (α-TO • ) with the concomitant formation of the ascorbate radical(Asc • ). Lipids (LH) are illustrated with grey-coloured circles with two hydrophobic tails andvitamin E with black circles with one hydrophobic tail in the schematic picture of a lipidmembrane. Note that in some lipids and vitamin E molecules, the hydrophobic tails are removedfor clarity.14