REDOX CYCLES OF VITAMIN-E - HYDROLYSIS AND ASCORBIC-ACID DEPENDENT REDUCTION OF 8A-(ALKYLDIOXY)TOCOPHERONES
REDOX CYCLES OF VITAMIN-E - HYDROLYSIS AND ASCORBIC-ACID DEPENDENT REDUCTION OF 8A-(ALKYLDIOXY)TOCOPHERONES
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DOI：
10.1021/bi00451a034
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发表时间：
1989-12-12
期刊：
影响因子：
2.9
通讯作者：
KENNEDY, TA
中科院分区：
文献类型：
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作者：
LIEBLER, DC;KAYSEN, KL;KENNEDY, TA
生物抗氧化剂α-生育酚(维生素E；TH)被过氧基氧化生成8a-(烷基二氧基)生育酚，它可以被水解为α-生育酚(TQ)，也可以被抗坏血酸还原以再生TH。为了确定这个可能的两电子TH氧化还原循环的化学成分，我们研究了8a-[(2，4-dimethyl-l-nitrilopent-2-yl)diox]tocopherone(1)在乙腈/缓冲液混合物和磷脂脂质体中的水解和还原。用分光光度法监测乙腈/缓冲液中TQ的生成，随着pH的升高，TQ的生成呈下降趋势，pH 4以上不能检测到TQ的生成。从1开始的TQ生成速率随时间的延长而增加，然后在一级终止阶段下降。8a-羟基-α-生育酚(2)重排为TQ的反应符合一级动力学，与TQ的生成终相相同。这两个速率常数都随着pH的降低而增大。1在乙腈/H_(18)O中水解生成[18O]TQ。这些观察结果表明，1失去了8a-(烷基二氧基)部分，产生生育酮阳离子(T+)，该阳离子可水解成TQ形成的中间体2。1或2与抗坏血酸在乙腈/缓冲液中孵育产生TH。1和2的还原均随pH的升高而降低。在pH为7的磷脂酰胆碱脂质体中，由1生成的T+约有10%被5 mM抗坏血酸还原为TH。这些结果共同证明，T+是两电子TH氧化还原循环中抗坏血酸可还原的中间体，这一过程可能需要生物催化才能在生物膜中进行。
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-l-nitrilopent-2-yl)diox]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 18O 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.