Structure−Activity Relationship of the Free-Radical-Scavenging Reaction by Vitamin E (α-, β-, γ-, δ-Tocopherols) and Ubiquinol-10:  pH Dependence of the Reaction Rates

Abstract

The reaction rates (ks) of vitamin E (alpha-, beta-, gamma-, delta-tocopherols, TocH), ubiquinol-10, and related antioxidants (tocol, ubiquinol-0, and hydroquinone) with aroxyl (ArO(.-)) radical have been measured in micellar solution by stopped-flow spectrophotometer. The ks values increased in the order of hydroquinone < tocol < delta-TocH < ubiquinol-0 < gamma-TocH approximately beta-TocH < ubiquinol-10 < alpha-TocH at pH 4 approximately 8. The antioxidants which have lower oxidation potentials showed higher reactivities. The ks values of alpha-, beta-, gamma-, delta-tocopherol, and tocol remained constant between pH 4 and 10, and decreased rapidly at pH 11 approximately 12 by increasing pH value. From the pH dependence of ks values, the pKa values (= 13.1 approximately 12.6) have been determined for these tocopherols. The ks values of ubiquinol-10 also remained constant between pH 4 and 9, and increased rapidly at pH 9.5. Ubiquinol-10 is dibasic acid and can exist in three different molecular forms, depending on the pH value. By comparing the ks values with the mole fraction of each molecular form of ubiquinol-10, the reaction rate ks1 (= 1.21 x 10(5) M(-1)s(-1)) for the undissociated form, ks2 (= 1.04 x 10(6) M(-1)s(-1)) for monoanion and ks3 (= 0 M(-1)s(-1)) for dianion, and the pKa1 and pKa2 values (= 11.4 and 12.7) were determined. The ks2 value is 8.6 times as large as the ks1 value. Similar analyses were performed for ubiquinol-0 and hydroquinone. It was found that the relative ratio of ks values (100:21:20:2.9) of alpha-, beta-, gamma-, delta-tocopherols in micellar dispersion has good correlation with the relative biopotency ratios for rat fetal resorption, rat hemeolysis, and chicken muscle dystrophy. The relative antioxidant activities of alpha-tocopherol and ubiquinol-10 have been discussed based on the ks values obtained and their concentrations in serum and several tissues (heart, muscle, liver, kidney, and brain).

Antiproliferative and Proapoptotic Effects of Tocopherol and Tocol on Activated Hepatic Stellate Cells

“…The free radical scavenging reactivity at pH 4-8 is in the order ␣-tocopherolϾ␤-tocopherolϭ␥-tocopherolϾ ␦-tocopherolϾtocol (18,30). Therefore, the antiproliferative effects of the four tocopherol isomers and tocol on HSCs and HSC-T6 cells appear to be different compared to their antioxidant activities.…”

Safety and efficacy of coenzyme Q10 supplementation in early chronic Peyronie's disease: a double-blind, placebo-controlled randomized study

“…7 Furthermore, an increase in oxidative stress has been postulated as potentially damaging for the tunica albuginea in acute phase of the disease. 8 Coenzyme Q 10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone, CoQ 10 ) is a fat-soluble, vitamin-like quinone commonly known as ubiquinone or ubidecarenone. Ubiquinone is reduced to ubiquinole (CoQ 10 H 2 ) via semiubiquinone radical (CoQ 10 H).…”

“…9 The fully reduced form of CoQ 10 (CoQ 10 H 2 ) exerts strong effects against the oxidative damage of polyunsaturated fatty acids. 10,11 It is to be noted that CoQ 10 is known to be the only endogenously synthesized lipid-soluble antioxidant. 9 Decreased CoQ 10 levels in serum, 12 as well as a decrease of the CoQ 10 H 2 /CoQ 10 ratio, 13 have been demonstrated in diseases associated with oxidative stress.…”

“…It has been reported that solubilized CoQ 10 suppresses the expression of TGF-b1 induced by dimethylnitrosamine in mouse liver and mouse embryonic fibroblast cells. 16 In addition, CoQ 10 activates NF-E2-related factor-2 (Nrf2). 16 Nrf2 overexpression itself reduces the basal expression of a-smooth muscle actin and TGF-b1.…”

“…16 Nrf2 overexpression itself reduces the basal expression of a-smooth muscle actin and TGF-b1. 16 Therefore, CoQ 10 -induced Nrf2 activation may suppress TGF-b1 expression. This study is the first prospective, double-blind, placebo-controlled randomized study on the effects of CoQ 10 supplementation in men with early chronic PD.…”