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| (R,R,R)-α-tocopherol |
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| CHEBI:18145 |
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| (R,R,R)-alpha-tocopherol |
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| An α-tocopherol that has R,R,R configuration. The naturally occurring stereoisomer of α-tocopherol, it is found particularly in sunflower and olive oils. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:46509, CHEBI:10336, CHEBI:12343
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| ChemicalBook:CB7132531, ChemicalBook:CB5275357, ChemicalBook:CB1275359, eMolecules:532461, eMolecules:29542088, ZINC000004095858 |
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Molfile
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SDF
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more structures >>
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-7.5438 3.5436 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9449 -6.3459 2.7866 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8188 -8.2764 5.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5236 -10.9828 5.9685 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4021 -5.2367 4.9243 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1459 -4.4864 2.9711 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1328 -3.3328 2.7429 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3631 -2.1064 2.2368 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3189 -0.9728 1.8499 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4888 0.2056 1.3326 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2751 -1.4744 0.7544 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2076 -0.3697 0.2312 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0023 0.2950 1.3654 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8238 -0.7165 2.1783 C 0 0 1 0 0 0 0 0 0 0 0 0 11.7838 -1.5049 1.2671 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6731 -2.4571 2.0828 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8231 -3.4860 2.8409 C 0 0 0 0 0 0 0 0 0 0 0 0 12.7151 -4.4149 3.6734 C 0 0 1 0 0 0 0 0 0 0 0 0 13.4270 -3.6320 4.7825 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8516 -5.5051 4.3104 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4908 -12.3924 6.0038 H 0 0 0 0 0 0 0 0 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Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 81 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| α-Tocopherol (alpha-tocopherol) is a type of vitamin E. Its E number is "E307". Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain, along with an aromatic ring is situated near the carbonyls in the fatty acyl chains of the phospholipid bilayer, allows for penetration into biological membranes. It is found most in the membrane's non-raft domains, associated with omega-3 and 6 fatty acids, to partially prevent oxidation. The most prevalent form, α-tocopherol, is involved in molecular, cellular, biochemical processes closely related to overall lipoprotein and lipid homeostasis. Compared to the others, α-tocopherol is preferentially absorbed and accumulated in humans.
Vitamin E is found in a variety of tissues, being lipid-soluble, and taken up by the body in a wide variety of ways. Ongoing research is believed to be "critical for manipulation of vitamin E homeostasis in a variety of oxidative stress-related disease conditions in humans." One of these disease conditions is the α-tocopherol role in the use by malaria parasites to protect themselves from the highly oxidative environment in erythrocytes. A second of these disease conditions is the α-tocopherol antioxidant properties' role cardiovascular heart disease. In preventing LDL (low-density lipoprotein) oxidation, it is able to decrease chances of atherosclerosis and arterial build-up. |
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Read full article at Wikipedia
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InChI=1S/C29H50O2/c1- 20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1 |
| GVJHHUAWPYXKBD-IEOSBIPESA-N |
| CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@]1(C)CCc2c(C)c(O)c(C)c(C)c2O1 |
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Mus musculus
(NCBI:txid10090)
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From MetaboLights
See:
MetaboLights Study
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Chlamydomonas reinhardtii
(NCBI:txid3055)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Homo sapiens
(NCBI:txid9606)
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Found in
faeces
(UBERON:0001988).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
saliva
(UBERON:0001836).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
cerebrospinal fluid
(UBERON:0001359).
See:
PubMed
|
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Homo sapiens
(NCBI:txid9606)
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Found in
blood
(UBERON:0000178).
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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Found in
breast milk
(ENVO:02000031).
See:
PubMed
|
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
(via tocol )
(via vitamin E )
food antioxidant
An antioxidant that used as a food additives to help guard against food deterioration.
(via alpha-tocopherol )
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EC 2.7.11.13 (protein kinase C) inhibitor
An EC 2.7.11.* (protein-serine/threonine kinase) inhibitor that interferes with the action of protein kinase C (EC 2.7.11.13).
immunomodulator
Biologically active substance whose activity affects or plays a role in the functioning of the immune system.
antiviral agent
A substance that destroys or inhibits replication of viruses.
micronutrient
Any nutrient required in small quantities by organisms throughout their life in order to orchestrate a range of physiological functions.
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
(via alpha-tocopherol )
algal metabolite
Any eukaryotic metabolite produced during a metabolic reaction in algae including unicellular organisms like chlorella and diatoms to multicellular organisms like giant kelps and brown algae.
food antioxidant
An antioxidant that used as a food additives to help guard against food deterioration.
(via alpha-tocopherol )
fat-soluble vitamin (role)
Any vitamin that dissolves in fats and are stored in body tissues. Unlike the water-soluble vitamins, they are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess.
(via vitamin E )
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nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
antiatherogenic agent
A cardiovascular drug that prevents atherogenesis, the accumulation of lipid-containing plaques on the innermost layers of the arteries. Compare with antiatherosclerotic agent. An agent that prevents blood clotting.
immunomodulator
Biologically active substance whose activity affects or plays a role in the functioning of the immune system.
food antioxidant
An antioxidant that used as a food additives to help guard against food deterioration.
(via alpha-tocopherol )
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View more via ChEBI Ontology
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Outgoing
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(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
algal metabolite
(CHEBI:84735)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
antiatherogenic agent
(CHEBI:50855)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
anticoagulant
(CHEBI:50249)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
antioxidant
(CHEBI:22586)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
antiviral agent
(CHEBI:22587)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
EC 2.7.11.13 (protein kinase C) inhibitor
(CHEBI:37700)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
immunomodulator
(CHEBI:50846)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
micronutrient
(CHEBI:27027)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
nutraceutical
(CHEBI:50733)
(R,R,R)-α-tocopherol
(CHEBI:18145)
has role
plant metabolite
(CHEBI:76924)
(R,R,R)-α-tocopherol
(CHEBI:18145)
is a
α-tocopherol
(CHEBI:22470)
(R,R,R)-α-tocopherol
(CHEBI:18145)
is enantiomer of
(S,S,S)-α-tocopherol
(CHEBI:46430)
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Incoming
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α-tocopheryloxyacetic acid
(CHEBI:194185)
has functional parent
(R,R,R)-α-tocopherol
(CHEBI:18145)
13-hydroxy-α-tocopherol
(CHEBI:84962)
has functional parent
(R,R,R)-α-tocopherol
(CHEBI:18145)
(S,S,S)-α-tocopherol
(CHEBI:46430)
is enantiomer of
(R,R,R)-α-tocopherol
(CHEBI:18145)
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(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-chromen-6-ol
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(+)-α-tocopherol
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UniProt
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(+)-alpha-tocopherol
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ChemIDplus
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(+)-α-tocopherol
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ChemIDplus
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(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol
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IUPAC
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(2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL
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PDBeChem
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(2R,4'R,8'R)-alpha-tocopherol
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ChemIDplus
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(2R,4'R,8'R)-α-tocopherol
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ChemIDplus
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(all-R)-α-tocopherol
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ChemIDplus
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(R,R,R)-α-tocopherol
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ChemIDplus
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5,7,8-trimethyltocol
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ChemIDplus
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alpha-Tocopherol
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KEGG COMPOUND
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d-α-tocopherol
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ChemIDplus
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RRR-α-tocopherol
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ChEBI
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Vitamin E
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KEGG COMPOUND
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5300493
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Beilstein Registry Number
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Beilstein
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59-02-9
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CAS Registry Number
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KEGG COMPOUND
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59-02-9
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CAS Registry Number
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NIST Chemistry WebBook
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59-02-9
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CAS Registry Number
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ChemIDplus
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94012
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Reaxys Registry Number
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Reaxys
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Aeschimann W, Kammer S, Staats S, Schneider P, Schneider G, Rimbach G, Cascella M, Stocker A (2021)
Engineering of a functional γ-tocopherol transfer protein.
Redox biology 38, 101773 [PubMed:33197771]
[show Abstract]
α-tocopherol transfer protein (TTP) was previously reported to self-aggregate into 24-meric spheres (α-TTPS) and to possess transcytotic potency across mono-layers of human umbilical vein endothelial cells (HUVECs). In this work, we describe the characterisation of a functional TTP variant with its vitamer selectivity shifted towards γ-tocopherol. The shift was obtained by introducing an alanine to leucine substitution into the substrate-binding pocket at position 156 through site directed mutagenesis. We report here the X-ray crystal structure of the γ-tocopherol specific particle (γ-TTPS) at 2.24 Å resolution. γ-TTPS features full functionality compared to its α-tocopherol specific parent including self-aggregation potency and transcytotic activity in trans-well experiments using primary HUVEC cells. The impact of the A156L mutation on TTP function is quantified in vitro by measuring the affinity towards γ-tocopherol through micro-differential scanning calorimetry and by determining its ligand-transfer activity. Finally, cell culture experiments using adherently grown HUVEC cells indicate that the protomers of γ-TTP, in contrast to α-TTP, do not counteract cytokine-mediated inflammation at a transcriptional level. Our results suggest that the A156L substitution in TTP is fully functional and has the potential to pave the way for further experiments towards the understanding of α-tocopherol homeostasis in humans. | de Sousa Rebouças A, Costa Lemos da Silva AG, Freitas de Oliveira A, Thalia Pereira da Silva L, de Freitas Felgueiras V, Cruz MS, Silbiger VN, da Silva Ribeiro KD, Dimenstein R (2019)
Factors Associated with Increased Alpha-Tocopherol Content in Milk in Response to Maternal Supplementation with 800 IU of Vitamin E.
Nutrients 11, E900 [PubMed:31013594]
[show Abstract]
BackgroundVitamin E supplementation might represent an efficient strategy to increase the vitamin E content in milk. The present study aimed to evaluate the impact of supplementation with 800 IU RRR-alpha-tocopherol on the alpha-tocopherol content of milk and the factors associated with the increase in vitamin E.MethodsRandomized clinical trial with 79 lactating women from Brazil, who were assigned to the control group, or to the supplemented group (800 IU of RRR-alpha-tocopherol). Milk and serum were collected between 30 and 90 days after delivery (collection 1), and on the next day (collection 2). Alpha-tocopherol was analyzed using high-performance liquid chromatography.ResultsIn the supplemented group, the alpha-tocopherol content in serum and milk increased after supplementation (p < 0.001). In the multivariate analysis, only alpha-tocopherol in milk (collection 1) was associated with the level of this vitamin in milk after supplementation (β = 0.927, p < 0.001), and binary logistic regression showed that the dietary intake was the only determinant for the greater effect of supplementation in milk.ConclusionThe pre-existing vitamin level in milk and diet are determinants for the efficacy of supplementation in milk, suggesting that in populations with vitamin E deficiency, high-dose supplementation can be used to restore its level in milk. | Aeschimann W, Staats S, Kammer S, Olieric N, Jeckelmann JM, Fotiadis D, Netscher T, Rimbach G, Cascella M, Stocker A (2017)
Self-assembled α-Tocopherol Transfer Protein Nanoparticles Promote Vitamin E Delivery Across an Endothelial Barrier.
Scientific reports 7, 4970 [PubMed:28694484]
[show Abstract]
Vitamin E is one of the most important natural antioxidants, protecting polyunsaturated fatty acids in the membranes of cells. Among different chemical isoforms assimilated from dietary regimes, RRR-α-tocopherol is the only one retained in higher animals. This is possible thanks to α-Tocopherol Transfer Protein (α-TTP), which extracts α-tocopherol from endosomal compartments in liver cells, facilitating its distribution into the body. Here we show that, upon binding to its substrate, α-TTP acquires tendency to aggregation into thermodynamically stable high molecular weight oligomers. Determination of the structure of such aggregates by X-ray crystallography revealed a spheroidal particle formed by 24 protein monomers. Oligomerization is triggered by refolding of the N-terminus. Experiments with cultured cell monolayers demonstrate that the same oligomers are efficiently transported through an endothelial barrier (HUVEC) and not through an epithelial one (Caco-2). Discovery of a human endogenous transport protein with intrinsic capability of crossing endothelial tissues opens to new ways of drug delivery into the brain or other tissues protected by endothelial barriers. | Kono N, Ohto U, Hiramatsu T, Urabe M, Uchida Y, Satow Y, Arai H (2013)
Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency.
Science (New York, N.Y.) 340, 1106-1110 [PubMed:23599266]
[show Abstract]
α-Tocopherol (vitamin E) transfer protein (α-TTP) regulates the secretion of α-tocopherol from liver cells. Missense mutations of some arginine residues at the surface of α-TTP cause severe vitamin E deficiency in humans, but the role of these residues is unclear. Here, we found that wild-type α-TTP bound phosphatidylinositol phosphates (PIPs), whereas the arginine mutants did not. In addition, PIPs in the target membrane promoted the intermembrane transfer of α-tocopherol by α-TTP. The crystal structure of the α-TTP-PIPs complex revealed that the disease-related arginine residues interacted with phosphate groups of the PIPs and that the PIPs binding caused the lid of the α-tocopherol-binding pocket to open. Thus, PIPs have a role in promoting the release of a ligand from a lipid-transfer protein. | Beer AM, Wegener T (2011)
[Vitamin E for gonarthrosis and coxarthrosis--results of a postmarketing surveillance study].
MMW Fortschritte der Medizin 153 Suppl 1, 14-20 [PubMed:21591326]
[show Abstract]
BackgroundInflammatory processes release reactive oxygen species, destroying cartilage tissue. Vitamin E is an antioxidant and protects cartilage tissue. Dietary intake of vitamin E is often low in patients with osteoarthrosis, and short term clinical studies have shown symptomatic relief in pain. Therefore, efficacy and tolerability of vitamin E are investigated in routine use of medical practitioners.Patients and methodsOpen, multicentric observational study including 151 patients with osteoarthritis (knee, hip): 85 patients were treated with 333,5 mg RRR-alpha-tocopherol (monotherapy), 61 patients with 333,5 mg RRR-alpha-tocopherol and a further analgesic (combination therapy). 5 patients (2 monotherapy, 3 combination) failed to turn up for follow-up (dropout). According to the study design, the physician was free in his treatment (assignment to treatment, choice of analgesic). After 4, 8, and 12 weeks the efficacy and tolerability were determined by physicians and by patients.ResultsDemographic data were comparable in both groups, however clinical condition was slightly worse in the combination group. In the course of the treatment, all parameters improved in both groups. Monotherapy was somewhat less effective and set on later. There were two adverse events in the monotherapy group (total endoprosthesis, itching). Tolerability of monotherapy was rated slightly better than combination therapy by physicians and by patients.ConclusionsFor patients with gonarthrosis or coxarthrosis the supplementation of Vitamin E to an analgetic medication is reasonable and well tolerated. | Dersjant-Li Y, Peisker M (2010)
Utilization of stereoisomers from alpha-tocopherol in livestock animals.
Journal of animal physiology and animal nutrition 94, 413-421 [PubMed:19663978]
[show Abstract]
Alpha-tocopherol derived from natural source is a single stereoisomer (i.e. RRR-alpha-tocopherol), whereas synthetic alpha-tocopherol consists of a mixture of eight stereoisomers, including RRR-, RRS-, RSR-, RSS-alpha-tocopherol (the 2R isomers, R configuration at positions 2' of the phytyl tail) and SRR-, SSR-, SRS- and SSS-alpha-tocopherol (the 2S isomers, S configuration at positions 2' of the phytyl tail). R and S are assigned by the sequence-rule procedure, i.e. the priorities of the substituents decrease in clockwise direction or anti-clockwise direction at each chiral centre. Not all these stereoisomers are equally bio-available, which can be explained by the differences in the rate of degradation, transportation and retention. Humans and livestock animals can only utilize the 2R forms, while the 2S forms have very low bio-availability or basically are not bio-available. The utilization of 2R forms differs between different animal species. For humans and livestock animals, RRR-alpha-tocopherol has the highest bio-availability compared with other stereoisomers, while other 2R forms have lower bio-availability compared with RRR-alpha-tocopherol. The relative bio-availability of RRR- and all-rac-alpha-tocopherol is related to animal species, ages of animals and assessment criteria. In general, recent literature studies have demonstrated that the relative bioavailability of RRR- and all-rac-alpha-tocopherol is 2:1, differing from the commonly used conversion factor of 1.36:1. The latter was based on rat-resorption-gestation test. Most recent studies have shown that this conversion factor of 1.36:1 is not applicable to livestock animals and based on other metabolic functions. When IU is required to express vitamin E activity, new conversion factors need to be defined for livestock animals. Quantitative determination of bio-availability of the individual alpha-tocopherol stereoisomers will give a more detailed picture of the bioavailability of natural and synthetic vitamin E forms. | Dersjant-Li Y, Jensen SK, Bos LW, Peisker MR (2009)
Bio-discrimination of alpha-tocopherol stereoisomers in rearing and veal calves fed milk replacer supplemented with all-rac-alpha-tocopheryl acetate.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 79, 199-211 [PubMed:20209471]
[show Abstract]
This study evaluated the biological discrimination of different alpha-tocopherol stereoisomers (i. e. RRR-, RRS-, RSR-, RSS- and the four 2S-alpha-tocopherols) from all-rac-alpha-tocopheryl acetate supplementation in milk replacer for rearing and veal calves respectively, in practical farming conditions. Two experiments were conducted. In experiment 1, six rearing calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 9 weeks. The calves were supplied calf starter concentrate from 1 to 12 weeks. In experiment 2, six veal calves were fed milk replacer supplemented with 80 mg/kg all-rac-alpha-tocopheryl acetate for a period of 24 weeks. Blood samples were taken at the start and every 4 weeks until 12 weeks for rearing calves in experiment 1, and until slaughter (24 weeks) for veal calves in experiment 2. Liver, adipose, muscle, and brain samples were taken at slaughter of the six veal calves in experiment 2. The distribution of different alpha-tocopherol stereoisomers in feed, plasma, and tissues was analyzed. In both experiments, it was observed that RRR-alpha-tocopherol was the dominant stereoisomer in plasma and tissues. The average percentage of the RRR-alpha-tocopherol stereoisomer was 64 %, and 39 % of the total alpha-tocopherol in plasma for rearing and veal calves, respectively. The higher RRR-alpha-tocopherol stereoisomer proportion as percentage of the total alpha-tocopherol in rearing calves was related to higher dietary natural vitamin E intake. Other 2R-alpha-tocopherol stereoisomers had lower utilization efficiency than RRR-alpha-tocopherol stereoisomer. 2S-alpha-tocopherol stereoisomers were basically not utilized by calves. | Slots T, Butler G, Leifert C, Kristensen T, Skibsted LH, Nielsen JH (2009)
Potentials to differentiate milk composition by different feeding strategies.
Journal of dairy science 92, 2057-2066 [PubMed:19389964]
[show Abstract]
To investigate the effect of the dietary intake of the cow on milk composition, bulk-tank milk was collected on 5 occasions from conventional (n = 15) and organic (n = 10) farms in Denmark and on 4 occasions from low-input nonorganic farms in the United Kingdom, along with management and production parameters. Production of milk based on feeding a high intake of cereals, pasture, and grass silage resulted in milk with a high concentration of alpha-linolenic acid (9.4 +/- 0.2 mg/kg of fatty acids), polyunsaturated fatty acids (3.66 +/- 0.07 mg/kg of fatty acids), and natural stereoisomer of alpha-tocopherol (RRR-alpha-tocopherol, 18.6 +/- 0.5 mg/kg of milk fat). A milk production system using a high proportion of maize silage, by-products, and commercial concentrate mix was associated with milk with high concentrations of linoleic acid (LA; 19.7 +/- 0.4 g/kg of fatty acids), monounsaturated fatty acids (27.5 +/- 0.3 mg/kg of fatty acids), and a high ratio between LA and alpha-linolenic acid (4.7 +/- 0.2). Comparing these 2 production systems with a very extensive nonorganic milk production system relying on pasture as almost the sole feed (95 +/- 4% dry matter intake), it was found that the concentrations of conjugated LA (cis-9,trans-11; 17.5 +/- 0.7 g/kg of fatty acids), trans-11-vaccenic acid (37 +/- 2 g/kg of fatty acids), and monounsaturated fatty acids (30.4 +/- 0.6 g/kg of fatty acids) were higher in the extensively produced milk together with the concentration of antioxidants; total alpha-tocopherol (32.0 +/- 0.8 mg/kg of milk fat), RRR-alpha-tocopherol (30.2 +/- 0.8 mg/kg of milk fat), and beta-carotene (9.3 +/- 0.5 mg/kg of milk fat) compared with the organic and conventional milk. Moreover, the concentration of LA (9.2 +/- 0.7 g/kg of fatty acids) in milk from the extensive milk production system was found to approach the recommended unity ratio between n-6 and n-3, although extensive milk production also resulted in a lower daily milk yield. | Wolf G (2007)
Estimation of the human daily requirement of vitamin E by turnover kinetics of labeled RRR-alpha-tocopherol.
Nutrition reviews 65, 46-48 [PubMed:17310859]
[show Abstract]
The human daily requirement of alpha-tocopherol was estimated by a determination of the turnover kinetics of deuterium-labeled RRR-alpha-tocopherol in two women and three men. The amount of alpha-tocopherol absorbed varied in proportion to the amount of fat eaten with the vitamin, increasing by 0.43 mg for each gram of fat consumed. A fat-free method for administering alpha-tocopherol was developed by vacuum impregnation of apples with the vitamin. Even in the absence of fat, about 10% of the administered alpha-tocopherol was absorbed. The daily requirement of alpha-tocopherol when consumed with a diet containing 21% fat was estimated to be 15 +/- 2 mg, an amount close to the current Estimated Average Requirement (EAR) of 12 mg/d. The study showed that vacuum-impregnated fruit might be a useful way to supplement vitamin E in people eating a low-fat diet. | Leichtle A, Teupser D, Thiery J (2006)
Alpha-tocopherol distribution in lipoproteins and anti-inflammatory effects differ between CHD-patients and healthy subjects.
Journal of the American College of Nutrition 25, 420-428 [PubMed:17031012]
[show Abstract]
ObjectiveThe purpose of this study was to investigate the dose-dependent effects of RRR-alpha-tocopherol supplementation in coronary heart disease (CHD) patients and healthy subjects on plasma alpha-tocopherol levels, plasma lipoprotein distribution, LDL oxidation, and inflammatory plasma markers.Methods12 patients with coronary heart disease and 12 healthy subjects were supplemented with increasing dosages of RRR-alpha-tocopherol at 100, 200 and 400 mg/day for a period of 3 weeks per dose. Lipoproteins were separated by FPLC and ultracentrifugation. Alpha-tocopherol was measured by HPLC. Resistance of LDL to oxidation was determined by reading the absorption at 234 nm after CuCl2-induced oxidation. Clinical chemistry and inflammatory markers were measured on automated analysis systems.ResultsPlasma alpha-tocopherol concentrations at baseline were comparable between CHD-patients and healthy subjects (21.7 +/- 4.7 micromol/L and 25.8 +/- 7.6 micromol/L, respectively). CHD-patients showed a significant increase (59%) of plasma alpha-tocopherol concentrations to 34.6 +/- 9.8 micromol/L at a dosage of 100 mg/day RRR-alpha-tocopherol, whereas healthy subjects showed a significant (54%) increase to 39.7 +/- 6.1 micromol/L only with 400 mg/day RRR-alpha-tocopherol. In addition, CHD-patients showed a significantly increased enrichment of alpha-tocopherol in VLDL. Supplementation (200 mg/day) caused a significant decrease of the acute phase plasma proteins C-reactive protein (CRP) (-65%) and fibrinogen (-24%).ConclusionOur data demonstrate that CHD-patients require lower dosages of alpha-tocopherol supplementation than healthy subjects to exert biological effects on plasma lipoproteins and acute phase response. | Jensen SK, Nørgaard JV, Lauridsen C (2006)
Bioavailability of alpha-tocopherol stereoisomers in rats depends on dietary doses of all-rac- or RRR-alpha-tocopheryl acetate.
The British journal of nutrition 95, 477-487 [PubMed:16512933]
[show Abstract]
The biological function of the stereoisomers of alpha-tocopherol is believed to depend on their bioavailability. Assessment of bioavailability within the body is therefore considered to be a good and easy way to predict biological value. The separation of alpha-tocopherol methyl ethers by chiral column HPLC is a good and easy tool with which to study the distribution of alpha-tocopherol stereoisomers. The objective of this investigation was to evaluate the bioavailability and distribution of the stereoisomers of alpha-tocopherol in the plasma and tissue in growing rats fed 25, 50, 100 or 200 mg/kg diet of either RRR- or all-rac-alpha-tocopheryl acetate for 10 d. The ratio between the two vitamin E sources based on their alpha-tocopherol concentration in plasma and tissues varied in the plasma between 1.04 and 1.74 and in tissues, ratios of 0.84-1.24 for liver, 0.34-1.59 for lung and 0.75-1.50 for spleen were obtained. An increasing dietary level of all-rac-alpha-tocopheryl acetate decreased the proportion of RRR-alpha-tocopherol, whereas the other stereoisomers were not affected. RRS-alpha-Tocopherol was present in the highest proportion, followed by RSR-, RSS- and RRR-alpha-tocopherol. In contrast to the other tissues and plasma, the liver contained the highest proportion (29-33 %) of the four 2S stereoisomers of total alpha-tocopherol. Rats fed RRR-alpha-tocopheryl acetate for 10 d showed a significant increase in the plasma and tissue content of RRR-alpha-tocopherol and a simultaneous decrease in the other three 2R isomers, whereas the absolute content of the 2S isomers was unaffected. In adipose tissue, concentrations of the three synthetic 2R isomers remained constant, whereas there was a steep increase in the content of RRR-alpha-tocopherol. | Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A (2003)
The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein.
Journal of molecular biology 331, 725-734 [PubMed:12899840]
[show Abstract]
Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL is the major determinant of plasma alpha-tocopherol levels in humans. Mutations in the alpha-TTP gene have been detected in patients suffering from low plasma alpha-tocopherol and ataxia with isolated vitamin E deficiency (AVED). The crystal structure of alpha-TTP reveals two conformations. In its closed tocopherol-charged form, a mobile helical surface segment seals the hydrophobic binding pocket. In the presence of detergents, an open conformation is observed, which probably represents the membrane-bound form. The selectivity of alpha-TTP for RRR-alpha-tocopherol is explained from the van der Waals contacts occurring in the lipid-binding pocket. Mapping the known mutations leading to AVED onto the crystal structure shows that no mutations occur directly in the binding pocket. | Min KC, Kovall RA, Hendrickson WA (2003)
Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency.
Proceedings of the National Academy of Sciences of the United States of America 100, 14713-14718 [PubMed:14657365]
[show Abstract]
Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central role in vitamin E homeostasis, preventing degradation of alpha-T by routing this lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding ATTP have been shown to cause a severe deficiency in alpha-T, which results in a progressive neurodegenerative spinocerebellar ataxia, known as ataxia with vitamin E deficiency (AVED). We have determined the high-resolution crystal structure of human ATTP with (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is sequestered deep in the hydrophobic core of the protein, implicating a large structural rearrangement for the entry and release of alpha-T. A comparison to the structure of a related protein, Sec14p, crystallized without a bona fide ligand, shows a possibly relevant open conformation for this family of proteins. Furthermore, of the known mutations that cause AVED, one mutation, L183P, is located directly in the binding pocket. Finally, three mutations associated with AVED involve arginine residues that are grouped together on the surface of ATTP. We propose that this positively charged surface may serve to orient an interacting protein, which might function to regulate the release of alpha-T through an induced change in conformation of ATTP. | Nielsen PB, Müllertz A, Norling T, Kristensen HG (2001)
The effect of alpha-tocopherol on the in vitro solubilisation of lipophilic drugs.
International journal of pharmaceutics 222, 217-224 [PubMed:11427352]
[show Abstract]
alpha-Tocopherol is an excellent solvent for many poorly soluble drugs. The aim of this work was to study whether or not the presence of alpha-tocopherol has an influence on the solubilisation of poorly soluble drugs in simulated intestinal fluids (SIF). The solubilizing capacity of mixed micelles containing alpha-tocopherol towards three lipophilic drugs was investigated. The solubilisation of alpha-tocopherol in an aqueous micellar phase was increased by the addition of monoglycerides (MG) and free fatty acids (FFA), preferably of medium chain length, as compared to a simple bile salt solution. The addition of alpha-tocopherol to mixed micellar solutions seems to have an effect on the solubilizing capacity, which can be correlated to the partition coefficient of the drug to be solubilised. A positive effect on the solubilisation of griseofulvin and felodipine was found. For a highly lipophilic drug (Lu28-179), a positive effect on solubilisation was observed only in media containing MG and FFA of medium chain length. Generally, alpha-tocopherol cannot be considered an important factor for the solubilisation of highly lipophilic drugs in SIF. The presence of lipolytic digestion products (LDP) of the proper chain length in relation to the drug to be solubilised is much more important. |
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