Tocopheronic acid

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

Vitamin E is absorbed in the gastrointestinal tract. Bile is necessary for absorption. Vitamin E is metabolized in the liver. The major metabolites of vitamin E are the glucuronides of tocopheronic acid. Vitamin E is distributed to all tissues. Lipid tissues store the vitamin for prolonged periods of time. Up to 30% is... 

Simon metabolites Initially, two major metabolites of a-tocopherol, the Simon metabolites (tocopheronic acid and tocopheronolactone) were described. Since they have a shortened side chain and an opened chroman structure, they are often quoted to demonstrate the antioxidant function of a-tocopherol in vivo. These metabolites are excreted in the urine as glucuronides or sulfates. The level of these metabolites increases markedly in the urine of healthy volunteers after a daily intake of 2 to 3 g all rac-a-tocopherol. 

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). 

The latter can be further reduced to a-tocopherolhydroquinone, which is secreted in bile and feces as a glucuronide conjugate (5). Other oxidative urinary metabolites include a-tocopheronic acid and 2,5,7,8-tetramethyI-2-(2 -carboxy-... 

In urine, a-tocopherol is excreted after transformation to a-tocopheronic acid, a-tocopheronolactone, and two other acids. Recently, a new metabolite, i.e., a-CEHC (2,5,7,8-tetramethyl-2-(2 -carboxyethyl)-6-hydroxychroman), has been isolated and identified by GC-MS (8,9). 

Chromanoxylium cation 4 preferably adds nucleophiles in 8a-position producing 8a-substituted tocopherones 6, similar in structure to those obtained by radical recombination between C-8a of chromanoxyl 2 and coreacting radicals (Fig. 6.4). Addition of a hydroxyl ion to 4, for instance, results in a 8a-hydroxy-tocopherone, which in a subsequent step gives the /zara-tocopherylquinone (7), the main (and in most cases, the only) product of two-electron oxidation of tocopherol in aqueous media. A second interesting reaction of chromanoxylium cation 4 is the loss of aproton at C-5a, producing the o-QM 3. This reaction is mostly carried out starting from tocopherones 6 or /zora-tocopherylquinone (7) under acidic catalysis, so that chromanoxylium 4 is produced in the first step, followed by proton elimination from C-5a. In the overall reaction of a tocopherone 6, a [ 1,4] -elimination has occurred. The central species in the oxidation chemistry of a-tocopherol is the o-QM 3, which is discussed in detail subsequently. 

Liebler, D.C., Kaysen, K.L., and Kennedy, T.A., Redox cycles of vitamin E hydrolysis and ascorbic acid dependent reduction of 8a-(alkyldioxy)tocopherones, Biochemistry 28 (25), 9Tll-Tni, 1989. 

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