Redox cycles of vitamin E: hydrolysis and ascorbic acid dependent reduction of 8a-(alkyldioxy)tocopherones

Abstract

Oxidation of the biological antioxidant alpha-tocopherol (vitamin E; TH) by peroxyl radicals yields 8a-(alkyldioxy)tocopherones, which either may hydrolyze to alpha-tocopheryl quinone (TQ) or may be reduced by ascorbic acid to regenerate TH. To define the chemistry of this putative two-electron TH redox cycle, we studied the hydrolysis and reduction of 8a-[(2,4-dimethyl-1-nitrilopent-2-yl)dioxy]tocopherone (1) in acetonitrile/buffer mixtures and in phospholipid liposomes. TQ formation in acetonitrile/buffer mixtures, which was monitored spectrophotometrically, declined with increasing pH and could not be detected above pH 4. The rate of TQ formation from 1 first increased with time and then decreased in a first-order terminal phase. Rearrangement of 8a-hydroxy-alpha-tocopherone (2) to TQ displayed first-order kinetics identical with the terminal phase for TQ formation from 1. Both rate constants increased with decreasing pH. Hydrolysis of 1 in acetonitrile/H2(18)O yielded [18O]TQ. These observations suggest that 1 loses the 8a-(alkyldioxy) moiety to produce the tocopherone cation (T+), which hydrolyzes to 2, the TQ-forming intermediate. Incubation of either 1 or 2 with ascorbic acid in acetonitrile/buffer yielded TH. Reduction of both 1 and 2 decreased with increasing pH. In phosphatidylcholine liposomes at pH 7, approximately 10% of the T+ generated from 1 was reduced to TH by 5 mM ascorbic acid. The results collectively demonstrate that T+ is the ascorbic acid reducible intermediate in a two-electron TH redox cycle, a process that probably would require biocatalysis to proceed in biological membranes.

Reactions of Peroxynitrite with γ-Tocopherol

“…The UV-vis spectra are similar to those previously reported for 8a-(hydroxy)-R-tocopherone (33,34), which readily arranges to R-tocopherylquinone. Because the 8a-substituted tocopherones readily undergo reduction by ascorbic acid to the corresponding tocopherols (28,29,33,34), we treated both products with ascorbic acid in sodium formate buffer (29). HPLC analysis revealed the disappearance of both products, with a concomitant increase in the formation of γ-TH.…”

Plasma antioxidant status in septic critically ill patients: a decrease over time

“…There is a co‐operative interaction between vitamin C and E in suppressing lipid peroxidation, the mixture of these two antioxidants is much more effective than the sum of both vitamins alone [23]. In addition, vitamin C regenerates α‐tocopherol from the vitamin E radical, when vitamin E acts as the primary antioxidant [24]. This point may be crucial in maintaining vitamin E in the normal range, as seen in this study and several other investigations [25,26,27].…”

Induction of Phase 2 Antioxidant Enzymes by Broccoli Sulforaphane: Perspectives in Maintaining the Antioxidant Activity of Vitamins A, C, and E

“…Cellular reductases, such as NQO1, may also play a role in the maintenance of cellular vitamin E. Oxidation of α-tocopherol yields a tocopherone intermediate that is further hydrolyzed to the primary oxidation product α-tocopherylquinone (TQ; Liebler et al, 1989). In vitro evidence suggests that α-tocopherol may be regenerated directly from α-tocopherones without further hydrolysis to the TQ oxidative product.…”

“…In vitro evidence suggests that α-tocopherol may be regenerated directly from α-tocopherones without further hydrolysis to the TQ oxidative product. This reaction may occur via a two-electron reduction, which is hypothesized to be catalyzed by a reductase similar to NQO1 (Liebler et al, 1989; Siegel et al, 1997). Whether this reaction occurs in vivo is yet to be demonstrated.…”