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Maret G Traber - One of the best experts on this subject based on the ideXlab platform.
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studies in humans using deuterium labeled α and γ Tocopherols demonstrate faster plasma γ Tocopherol disappearance and greater γ metabolite production
Free Radical Biology and Medicine, 2005Co-Authors: Scott W. Leonard, Rajasekhar Ramakrishnan, Elaine Paterson, Jeffrey Atkinson, Carroll E Cross, Maret G TraberAbstract:Abstract We hypothesized that human plasma α- and γ-Tocopherol concentrations reflect differences in their kinetics, especially influenced by γ-Tocopherol metabolism. Vitamin E kinetics were evaluated in humans ( n = 14) using ∼50 mg each of an equimolar ratio of d 6 -α- and d 2 -γ-tocopheryl acetates administered orally. Mass spectrometry was used to measure deuterated plasma Tocopherols, as well as plasma and urinary vitamin E metabolites, α- and γ-carboxyethylhydroxychromans (CEHCs). Plasma d 2 -γ-Tocopherol fractional disappearance rates (FDR; 1.39 ± 0.44 pools/day, mean ± SD) were more than three times greater than those of d 6 -α-Tocopherol (0.33 ± 0.11, p d 2 -γ-Tocopherol half-life was 13 ± 4 h compared with 57 ± 19 for d 6 -α-Tocopherol. Whereas neither plasma nor urinary d 6 -α-CEHC was detectable (limit of detection 1 nmol/L), γ-CEHC (labeled plus unlabeled) increased from 129 ± 20 to 258 ± 40 nmol/L by 12 h and returned to baseline by 48 h; at 12 h d 2 -γ-CEHC represented 54 ± 4% of plasma γ-CEHC. Women compared with men had a greater d 2 -γ-Tocopherol FDR ( p d 2 -γ-CEHC concentration ( p p d 2 -γ-CEHC ( p
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Incorporation of deuterated RRR- or all-rac-α-Tocopherol in plasma and tissues of α-Tocopherol transfer protein–null mice
The American Journal of Clinical Nutrition, 2002Co-Authors: Scott W. Leonard, Yuko Terasawa, Robert V. Farese, Maret G TraberAbstract:BACKGROUND: Most vitamin E supplements contain synthetic all-rac-alpha-Tocopherol [2,5,7,8-tetramethyl-2RS-(4'RS,8'RS,12-trimethyltridecyl)-6-chromanol] with 8 stereoisomers; only 1 is identical to the natural stereoisomer, RRR-alpha-Tocopherol [2,5,7,8-tetramethyl-2R-(4'R,8'R,12-trimethyltridecyl)-6-chromanol]. In humans, 2R-alpha-Tocopherol stereoisomers are preferentially maintained in the plasma, a function that has been attributed to hepatic alpha-Tocopherol transfer protein (alpha-TTP), but this hypothesis has not been tested. OBJECTIVE: We sought to determine the functions of alpha-TTP by comparing mice that express alpha-TTP with mice that are genetically unable to express alpha-TTP. DESIGN: Adult alpha-TTP null (Ttpa(-/-); n = 5), heterozygous (Ttpa(+/-); n = 7), and wild-type (Ttpa(+/+); n = 3) mice consumed equimolar RRR-alpha-[5,7-(C(2)H(3))(2)]-(d(6))- and all-rac-alpha-[5-(C(2)H(3))]-(d(3))-tocopheryl acetates (30 mg/kg diet each) for 3 mo. Subsequently, we measured labeled and unlabeled alpha-Tocopherols in plasma and 17 tissues. RESULTS: In all mice, plasma and tissue d(6)- + d(3)-alpha-Tocopherols represented approximate 80-90% of total alpha-Tocopherol. In the Ttpa(-/-) mice, low total alpha-Tocopherol concentrations were found in plasma (5.4%) and most other tissues (2-20%), but liver concentrations were 39% of those of Ttpa(+/+) mice. Peripheral tissue ratios of d(6)- to d(3)-alpha-Tocopherol were 1.1 plus minus 0.1 and 1.8 plus minus 0.2 in Ttpa(-/-) and Ttpa(+/+) mice, respectively (P < 0.0001), showing that alpha-TTP preferentially selects 2R-alpha-Tocopherols for secretion into plasma. This 2:1 ratio does not support the currently defined international unit of 1.36:1 RRR-alpha-Tocopherol to all-rac-alpha-Tocopherol. CONCLUSION: Deletion of the alpha-TTP gene in mice results in an accumulation of dietary alpha-Tocopherol in the liver and depletion of peripheral tissue alpha-Tocopherol.
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vitamin e function and metabolism
The FASEB Journal, 1999Co-Authors: Regina Brigeliusflohe, Maret G TraberAbstract:Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of Tocopherols and tocotrienols, of which α-Tocopherol has the highest biological activity. Due to the potent antioxidant properties of Tocopherols, the impact of α-Tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the α-Tocopherol transfer protein in the liver specifically sorts out RRR-α-Tocopherol from all incoming Tocopherols for incorporation into plasma lipoproteins, and that α-Tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of Tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, γ-Tocopherol might have functions apart from ...
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Vitamin E: function and metabolism
The FASEB Journal, 1999Co-Authors: Regina Brigelius-flohé, Maret G TraberAbstract:Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of Tocopherols and tocotrienols, of which alpha-Tocopherol has the highest biological activity. Due to the potent antioxidant properties of Tocopherols, the impact of alpha-Tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the alpha-Tocopherol transfer protein in the liver specifically sorts out RRR-alpha-Tocopherol from all incoming Tocopherols for incorporation into plasma lipoproteins, and that alpha-Tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of Tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, gamma-Tocopherol might have functions apart from being an antioxidant. It is a nucleophile able to trap electrophilic mutagens in lipophilic compartments and generates a metabolite that facilitates natriuresis. The metabolism of vitamin E is equally unclear. Excess alpha-Tocopherol is converted into alpha-CEHC and excreted in the urine. Other Tocopherols, like gamma- and delta-Tocopherol, are almost quantitatively degraded and excreted in the urine as the corresponding CEHCs. All rac alpha-Tocopherol compared to RRR-alpha-Tocopherol is preferentially degraded to alpha-CEHC. Thus, there must be a specific, molecular role of RRR-alpha-Tocopherol that is regulated by a system that sorts, distributes, and degrades the different forms of vitamin E, but has not yet been identified. In this article we try to summarize current knowledge on the function of vitamin E, with emphasis on its antioxidant vs. other properties, the preference of the organism for RRR-alpha-Tocopherol, and its metabolism to CEHCs.
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human plasma and tissue alpha Tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin e
The American Journal of Clinical Nutrition, 1998Co-Authors: Graham W Burton, L Hughes, Herbert J. Kayden, Maret G Traber, R V Acuff, D N Walters, K U IngoldAbstract:Abstract We report a comparison of natural and synthetic vitamin E in humans using deuterium labeling to permit the two forms of vitamin E to be measured independently in plasma and tissues of each subject. Differences in natural and synthetic vitamin E concentrations were measured directly under equal dosage conditions using an equimolar mixture of deuterated RRR-alpha-tocopheryl acetate and all-rac-alpha-tocopheryl acetate. Two groups of five adults took 30 mg of the mixture as a single dose and as eight consecutive daily doses, respectively. After a 1-mo interval the schedule was repeated but with a 10-fold higher dose (ie, 300 mg). In each case, the ratio of plasma d3-RRR-alpha-Tocopherol to d6-all-rac-alpha-Tocopherol (RRR:rac) increased from approximately 1.5-1.8 to approximately 2 after dosing ended. In an elective surgery study in which 22 patients were given 150 mg/d for up to 41 d before surgery, the RRR:rac in tissues was lower than in plasma and the percentage of deuterated alpha-Tocopherol was lower in all tissues except gallbladder and liver. In a terminally ill patient given 30 mg/d for 361 d, plasma and tissue (x+/-SD) RRR-rac ratios (and % deuterated alpha-Tocopherol) at autopsy were 2.06 (6.3%) and 1.71+/-0.24 (5.9+/-2.2%), respectively. In a second terminally ill patient given 300 mg/d for 615 d, the corresponding values were 2.11 (68%) and 2.01+/-0.17 (65+/-10%), respectively. The results indicated that natural vitamin E has roughly twice the availability of synthetic vitamin E. This 2:1 ratio is significantly higher than the currently accepted RRR:rac of 1.36:1.00. Gamma-Tocopherol, expressed as a fraction of total unlabeled Tocopherols in 15 elective surgery patients, was 1.4-4.6 (mean: 2.6) times greater in adipose tissue, muscle, skin, and vein than in plasma, which is a substantially larger fraction than had been recognized previously.
Mirjana Minceva - One of the best experts on this subject based on the ideXlab platform.
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computational solvent system screening for the separation of Tocopherols with centrifugal partition chromatography using deep eutectic solvent based biphasic systems
Journal of Chromatography A, 2017Co-Authors: Franziska Bezold, Maria E Weinberger, Mirjana MincevaAbstract:Abstract Tocopherols are a class of molecules with vitamin E activity. Among those, α-Tocopherol is the most important vitamin E source in the human diet. The purification of Tocopherols involving biphasic liquid systems can be challenging since these vitamins are poorly soluble in water. Deep eutectic solvents (DES) can be used to form water-free biphasic systems and have already proven applicable for centrifugal partition chromatography separations. In this work, a computational solvent system screening was performed using the predictive thermodynamic model COSMO-RS. Liquid-liquid equilibria of solvent systems composed of alkanes, alcohols and DES, as well as partition coefficients of α-Tocopherol, β-Tocopherol, γ-Tocopherol, and σ-Tocopherol in these biphasic solvent systems were calculated. From the results the best suited biphasic solvent system, namely heptane/ethanol/choline chloride-1,4-butanediol, was chosen and a batch injection of a Tocopherol mixture, mainly consisting of α- and γ-Tocopherol, was performed using a centrifugal partition chromatography set up (SCPE 250-BIO). A separation factor of 1.74 was achieved for α- and γ-Tocopherol.
Angelo Azzi - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanism of α Tocopherol action
Free Radical Biology and Medicine, 2007Co-Authors: Angelo AzziAbstract:The inability of other antioxidants to substitute for α-Tocopherol in a number of cellular reactions, the lack of a compensatory antioxidant response in the gene expression under conditions of α-Tocopherol deficiency, the unique uptake of α-Tocopherol relative to the other Tocopherols and its slower catabolism, and the striking differences in the molecular function of the different Tocopherols and tocotrienols, observed in vitro, unrelated to their antioxidant properties, are all data in support of a nonantioxidant molecular function of α-Tocopherol. Furthermore, in vivo studies have also shown that α-Tocopherol is not able, at physiological concentrations, to protect against oxidant-induced damage or prevent disease allegedly caused by oxidative damage. α-Tocopherol appears to act as a ligand of not yet identified specific proteins (receptors, transcription factors) capable of regulating signal transduction and gene expression.
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vitamin e non antioxidant roles
Progress in Lipid Research, 2000Co-Authors: Angelo Azzi, Achim StockerAbstract:Abstract Vitamin E was originally considered a dietary factor of animal nutrition especially important for normal reproduction. The significance of vitamin E has been subsequently proven as a radical chain breaking antioxidant that can protect the integrity of tissues and play an important role in life processes. More recently α-Tocopherol has been found to possess functions that are independent of its antioxidant/radical scavenging ability. Absorption in the body is α-Tocopherol selective and other Tocopherols are not absorbed or are absorbed to a lesser extent. Furthermore, pro-oxidant effects have been attributed to Tocopherols as well as an anti-nitrating action. Non-antioxidant and non-pro-oxidant molecular mechanisms of Tocopherols have been also described that are produced by α-Tocopherol and not by β-Tocopherol. α-Tocopherol specific inhibitory effects have been seen on protein kinase C, on the growth of certain cells and on the transcription of some genes (CD36, and collagenase). Activation events have been seen on the protein phosphatase PP2A and on the expression of other genes (α-tropomyosin and Connective Tissue Growth Factor). Non-antioxidant molecular mechanisms have been also described for γ-Tocopherol, δ-Tocopherol and tocotrienols.
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Vitamin E: Non-antioxidant roles
Progress in Lipid Research, 2000Co-Authors: Angelo Azzi, Alexander StockerAbstract:Vitamin E was originally considered a dietary factor of animal nutrition especially important for normal reproduction. The significance of vitamin E has been subsequently proven as a radical chain breaking antioxidant that can protect the integrity of tissues and play an important role in life processes. More recently α-Tocopherol has been found to possess functions that are independent of its antioxidant/radical scavenging ability. Absorption in the body is α-Tocopherol selective and other Tocopherols are not absorbed or are absorbed to a lesser extent. Furthermore, pro-oxidant effects have been attributed to Tocopherols as well as an anti-nitrating action. Non-antioxidant and non-pro-oxidant molecular mechanisms of Tocopherols have been also described that are produced by α-Tocopherol and not by β-Tocopherol. α-Tocopherol specific inhibitory effects have been seen on protein kinase C, on the growth of certain cells and on the transcription of some genes (CD36, and collagenase). Activation events have been seen on the protein phosphatase PP2A and on the expression of other genes (α-tropomyosin and Connective Tissue Growth Factor). Non-antioxidant molecular mechanisms have been also described for γ-Tocopherol, δ-Tocopherol and tocotrienols. © 2000 Elsevier Science Ltd.
Wolfgang Bilger - One of the best experts on this subject based on the ideXlab platform.
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Screening of microalgae and cyanobacteria strains for α-Tocopherol content at different growth phases and the influence of nitrate reduction on α-Tocopherol production
Journal of Applied Phycology, 2017Co-Authors: Opayi Mudimu, Inga Klara Koopmann, Nataliya Rybalka, Thomas Friedl, Rüdiger Schulz, Wolfgang BilgerAbstract:Tocopherols (vitamin E) are only synthesized by photosynthetic organisms and have wide applications in cosmetics and as dietary supplements in human nutrition and aquaculture. Tocopherols from microalgae and cyanobacteria are rarely investigated, and little is known about their contents. Therefore, 130 strains of cultured microalgae and cyanobacteria were analyzed for α-Tocopherol content under various culture conditions. The growth phase had a significant effect on content of α-Tocopherol. Maximal amounts were observed at the stationary growth phase. Reduction of nitrate concentration in media caused an increased production of α-Tocopherol. The contents were significantly enhanced when the nitrate concentration was reduced to one fourth in culture media used. The content of α-Tocopherol was found to reflect phylogenetic relationships at the level of classes, with classes of Rhodophyta and Cyanobacteria accumulating the lowest contents. Within each class, contents varied widely at the species level emphasizing the importance of extensive screening procedures for the identification of strains with high α-Tocopherol contents.
Franziska Bezold - One of the best experts on this subject based on the ideXlab platform.
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computational solvent system screening for the separation of Tocopherols with centrifugal partition chromatography using deep eutectic solvent based biphasic systems
Journal of Chromatography A, 2017Co-Authors: Franziska Bezold, Maria E Weinberger, Mirjana MincevaAbstract:Abstract Tocopherols are a class of molecules with vitamin E activity. Among those, α-Tocopherol is the most important vitamin E source in the human diet. The purification of Tocopherols involving biphasic liquid systems can be challenging since these vitamins are poorly soluble in water. Deep eutectic solvents (DES) can be used to form water-free biphasic systems and have already proven applicable for centrifugal partition chromatography separations. In this work, a computational solvent system screening was performed using the predictive thermodynamic model COSMO-RS. Liquid-liquid equilibria of solvent systems composed of alkanes, alcohols and DES, as well as partition coefficients of α-Tocopherol, β-Tocopherol, γ-Tocopherol, and σ-Tocopherol in these biphasic solvent systems were calculated. From the results the best suited biphasic solvent system, namely heptane/ethanol/choline chloride-1,4-butanediol, was chosen and a batch injection of a Tocopherol mixture, mainly consisting of α- and γ-Tocopherol, was performed using a centrifugal partition chromatography set up (SCPE 250-BIO). A separation factor of 1.74 was achieved for α- and γ-Tocopherol.
