Tocopherol metabolites

The selectivity of higher organisms for a-tocopherol has been impressively demonstrated in recent years by analysing the metabolism of vitamin E. Excess a-tocopherol and the other tocopherol analogs are extensively metabolized before excretion. This finding suggests that the organism maintains the correct vitamin E level by selective retention of a-tocopherol, and by specific metabolism of all the other tocopherols and of the excess a-tocopherol. Keep in mind that the tocopherol metabolites can also act as bioactive compounds, which can bind to... 

The tocopherols may be metabolized to bioactive compounds, such as Simon metabolites, CEHCs, or tocopheryl quinones (see sections on tocopherol metabolites and tocopheryl quinones), which can bind to transcription factors and enzymes and modulate their activity. 

Experiments performed by Corwin and Schwarz (1960) gave evidence that the a-tocopherol metabolite (X) (Fig. 7) exerts tocopherol-like activity in the respiratory decline test. In order to mal e some material available for further biological testing, the tritium-labeled y-lactone (X) was synthesized following the lines given by Weichet et al. (1959) ... 

Fig. 4. The tocopherol metabolite of Simon et al. (1956). 2-(3-Hydroxy-3-methyl-5-carboxypentyl)-3,5,6-trimethylbenzoquinone (I) and its v-lactone (II).

Frank, J., Kamal-Eldin, A., and Traber, M.G., Consumption of sesame oil muffins decreases the urinary excretion of -y-tocopherol metabolites in humans, Ann. N.Y. Acad. Sci., 1031, 365-367, 2004. 

Nonaqueous Systems In nonaqueous (nonpolar) solvent systems, nitrosatlon also proceeds. In these solvents, alpha-tocopherol acts as a lipid soluble blocking agent in much the same fashion as ascorbic acid functions in the aqueous phase. Alpha-tocopherol reacts with a nitrosating agent and reduces it to nitric oxide. At the same time, alpha-tocopherol is oxidized to tocoquinone, which is the first oxidation product of vitamin E and also a normal metabolite in vivo. 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

Consequently, soil samples from feedlots have a dual origin of toco-pherols. This is illustrated with the GC-MS data of a study done in the San Joaquin Valley of California (Fig. 5b, ). The y-tocopherol is derived exclusively from the vegetation fodder, while a-tocopherol is derived from both vegetation and the hydrolysis of the tocopheryl acetate feed supplement. Excess a-tocopherol acetate, not hydrolyzed in the animal gut, is also present. Because a-tocopherol acetate is relatively stable, its presence in soil dust samples indicates the level of its usage as a feed supplement. A significant metabolite of a-tocopherol elutes after the acetate and the... 

Fig. 5. Examples of GC-MS data for vitamin E in a vegetable oil and cattle feedlot soil (a) vegetable oil, sum of key ions mjz 129 (TMS for sterols), 474, 488 and 502 of tocopherols as TMS), (b) feedlot soil, sum of key ions ra/z 416 and 430 for tocopherols, a-tocopheryl acetate, and the metabolite (as free phenols), and (c) mass spectrum of a-tocopherol hydroquinone (V).

Table 6.6 indicates that the diet-derived PPT metabolites are able thermodynamically to scavenge some or all of the damaging radicals should they come into contact. However, these metabolites are so hydrophilic, e.g., quercetin-3-glucuronide (Ai= 0.008) " compared with quercetin and a-tocopherol (if = 550), that it is unlikely they will encounter... 

While the angiotensins promote release of aldosterone, the atrial natriuretic hormoner aa cc inhibits release. This group of 21- to 33-residue polypeptides, secreted by cells of the atria (auricles) of the heart, also inhibits release of renin and promotes secretion of both Na+ and water. Thus, they antagonize the action of aldosterone, which promotes Na+ retention. However, there is uncertainty as to the significance of these peptides. The following metabolite of y-tocopherol (Fig. 15-24) has been isolated from urine and is proposed as a new endogenous natriuretic factor.dd... 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

Plants are significant to the diet of humans and animals since they provide most of the essential nutrients and vitamins. Vitamins C (ascorbic acid), E (a-tocopherol) and K (phylloquinone) are biosynthesized by plants, while (3-carotene, the precursor of vitamin A and ergosterol, the precursor of vitamin D, are also secondary plant metabolites. These metabolites are used in folk medicine and for industrial purposes, as raw materials for pharmaceutical and other products [3]. On the other hand, plants may produce substances, which are toxic and/or irritant to man. 

Another important field of application concerns food and beverages, especially wine, juices, and tea (A2, A11, A17, B4, K12, V7, Yl). The antioxidant components of food include vitamin E (a-tocopherol), vitamin A (retinoids), vitamin C (ascorbic acid), and also fi-carotene (provitamin A), other carotenoids (of which more than 600 compounds have been identified), flavonoids, simple phenols, and glucobrasicins (H3). Unfortunately, the TAC value of a food is not informative on the bioavailability of its antioxidants. It has been estimated that polyphenols are normally present in blood plasma at concentrations of 0.2-2 //M (PI). However, it has been demonstrated that feeding rats a quercetin-augmented diet can increase their plasma levels of quercetin and its metabolites up to 10-100 //M (M27), and transient increases in the concentration of plant-derived phenolic compounds can take place after ingestion of food and beverages, which may affect blood plasma TAC (see later). 

The reason for this increase in mortality is considered to be due to the displacement of other fat-soluble antioxidant such as y-tocopherol (29) and to the possible inhibition of the cytosolic glutathione S-transpherase, which is involved in the detoxification process of endogenous toxins (30). One of the oxidized metabolites of vitamin E, the vitamin E quinone, has a very strong activity as an inhibitor of vitamin Independent clotting mechanism (3 I),... 

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