Quinones, Hydroquinones, and Tocopherols

As shown in Figure 4.3, tocopherol can undergo reversible oxidation to an epoxide, followed by ring cleavage to yield a quinone, which is reduced to the hydroquinone and conjugated with glucuronic acid, for excretion in the bile, which is the major route of excretion. The side chain of the quinone and... 

The most interesting reactions of the natural quinone-hydroquinone pairs are (a) their reversible one-electron redox reactions, (b) the Michael reactions of quinones, and (c) the formation of polyquinones. Oxidation of tocopherol with FeClj leads to a cleavage of the enol ether and quinone formation (Scheme 7.2.2). 

Studies of the metabolism of vitamin E were triggered by the observations of Alaupovic and coworkers [126, 127]. When " [Cj-D-a-tocopherol-5-methyl was administered to rats or pigs and attempts were made to detect metabolic derivatives, two compounds were separated by chromatography. One of the compounds is " [C]-D-a-tocopherol quinone the other is either a dimer or a trimer of a-tocopherol. The dimer and trimer are terminal oxidation products of a-tocopherol and are excreted in the bile. a-Tocopherol quinone can be converted to a-hydroquinone. a-Tocopherol hydroquinone may be esterified in liver and eliminated in the feces after concentration in the bile and excretion in the intestine, or it may be oxidized in the kidney to a-tocopheronic acid, which may be converted into an a-tocopheronolactone conjugate, which is excreted in the urine. In conclusion, vitamin E is excreted as such in the urine or the bile after conversion to a dimer or a trimer, in the form of a conjugated hydroxy-quinone or tocopheronic acid (see Fig. 4-43). 

Tocopherols and tocotrienols are monoethers of the respective hydroquinones and are therefore readily oxidised, for example by ferric ions, Hpid hydroperoxides and other oxidants. This creates the corresponding quinones (tocopheryl quinones or tocoquinones). Tocopheryl quinones can be reduced to tocopheryl hydroquinones (tocohydroquinones). The most important reactions are those with oxidised lipids (Figures 5.7 and 5.8). 

In contrast to photosynthetic bacteria the photosynthetic apparatus of algae and higher plants comprises a uniform prenylquinone composition (Table 3) with plastoquinone-9 + its hydroquinone (PQ-9 + PQ-9.H2) as the major component and smaller amounts of phylloquinone (vitamin K ) and o<-tocoquinone (o -TQ) (1,2). All three prenylquinones are potential photosynthetic electron carriers. The role of -tocopherol, the cyclic form of the reduced ol-tocoquinone, seems to be primarily that of a lipid antioxidant. In older, in senescent or chromoplast-bearing tissue other plastoquinone-forms (plasto-quinone B and C) may show up, or in etiolated tissue there are biosynthetic precursors of and o(-TQ (for literature see 2,17,18), but these minor quinone components do not play any role in photosynthesis. 

Tocopherol carries six methyl groups three on the hydroquinone ring and three on the side chain. The three chiral centers are all of R configuration (2-R, 4 -R, 8 -R). The most significant chiral center at C2 is as stable to oxidative cleavage as the remote centers at C4 and C8, but it disappears, of course, upon oxidation to the quinone (see Scheme 7.2.1). The UV spectrum shows a maximum at 284 nm (e = 30,000) in petrol ether and at 292 nm in ethanol. Quantitative determination in food occurs by extraction with ether, HPLC, and reduction of Fe(III) ions to Fe(II). The iron(II) concentration is then determined colorimet-rically with 2,2 -dipyridyl = 520 nm) or 4,7-diphenyl-1,10-phenanthrolin. Solutions of free tocopherol fluoresce in the UV( ), whereas neither tocopherol acetate nor the quinone shows any fluorescence (Lang, 1974 Isler and Bmbacker, 1982). This phenomenon is not understood. 

Quinones are firmly established in photosynthesis models. But how about vitamins E and K How do quinones work in animals First of all they transport electrons in a similar way as in photosynthesis (Metzler, 1977 Voet, 1990). Second, tocopherol is known to act as an antioxidant or radical quencher. The radical chain starting with the decomposition of unsaturated lipid peroxides, for example, is inhibited by tocopherol, which produces long-lived semiquinone radicals (Scheme 7.2.10). Vitamin E prevents, for example, sterility in rats fed rancid lipids. Vitamin E in connection with carotenes is also used as a stabilizer for diet margarines containing large amounts of essential fatty acids. Another possible activity of tocopherol is participation in oxidative phosphorylation a hydroquinone is mono-esterified with phosphoric acid to form a quinol phosphate and then oxidized to the quinone. The cationic quinone-phosphate adduct then reacts with anionic phosphate to form pyrophosphate (Scheme 7.2.10), (Wang, 1969 Breslow, 1980 Isler and Brubacher, 1982). 

The tocopherols are converted by oxidation to tocopheryl quinones, which upon reduction become tocopheryl hydroquinones. The reduction of a-tocopheryl quinone to a-tocopheryl hydroquinone occurs either via NADPH-cytochrome P45Q reductase, NAD(P)H quinone oxidoreductase 1, or ascorbate for the other tocopherols these pathways have not been tested. The tocophrayl hydroquinones can regenerate the toeopheroxyl radical and thus preserve a-tocophraol with different effieieneies (a > p > y-toeopheryl hydroquinone). ... 

Standards a-, P-, y-, and 8-Tocopherols, tocopherol quinones, tocopherol hydroquinones TMS derivatives GC-MS Rtx-5MS column, temperature 220-290°C 0-15 ng tocopherols 40 pg/pL for all tocopherols Melchert et al. (2002)... 

Numerous examples of couplings between hydroquinone, paro-quinone or toluquinone and a linear terpenic chain have been observed in Dictyotales and Fucales. Most prenylquinones and prenylated hydroquinones have a diterpenic chain and a methyl on the aromatic ring. The analogy with tocopherols and vitamin K is clear, and these compounds may be active as antioxidants and/or antiradicals (Isler and Montavon, 1965 Fisch et al, 2003). The following examples are intended to illustrate these observations. 

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