Drug nameVitamin E
DescriptionA generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids. [PubChem]
DrugBankPrimary Accession Number: DB00163
DINNot available
TypeApproved, Nutraceutical, Small Molecule
IndicationVitamin E, known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer`s, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.
Mechanism of ActionAlthough all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin`s biological activity. Vitamin E`s anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis. Vitamin E`s antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade. The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system. The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity. Lastly, the mechanism of action of vitamin E`s antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.
Absorption50 to 80% absorbed from gastrointestinal tract
ToxicityNot available
Protein BindingBound to beta-lipoproteins in blood.
Interactions
RXListNot available
KEGGdrug: Not available / compound: C02477
PubChemcompound: 14985 / substance: 5492
PharmGKBPA451900
Metabolizing Enzymes
NameGeneEntrezIDUniprotSNP
Glutathione S-transferase A2GSTA22939P09210rs13306279
Xanthine dehydrogenase/oxidaseXDH7498P47989rs4986871
Target
NameGeneEntrezIDSwissprotSNP
Arachidonate 5-lipoxygenaseALOX5240LOX5_HUMANrs55854006 rs2229136 rs45598533 rs34852267 s28395870 rs28395861 rs12762604 rs2228065 rs2228064 rs1803918
Diacylglycerol kinase alphaDGKA1606DGKA_HUMANrs1052206 rs34323718 rs17852990 rs17118135 rs11834873 rs7966319 rs1395282 rs1136082
Orphan nuclear receptor PXRNR1I28856PXR_HUMANrs56162473 rs4058490 rs59371185 rs35761343 rs12721612 rs12721613 rs1140969 rs1140968 rs2229856 rs1063955 rs12721611 rs12721600
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoformPPP2CA5515PP2AA_HUMANrs34258631 rs11552681 rs1803925
Serine/threonine-protein phosphatase 2A catalytic subunit beta isoformPPP2CB5516PP2AB_HUMANrs11549961
Protein kinase C alpha typePRKCA5578KPCA_HUMANrs6504459 rs56286405 rs55707360 rs2227857 rs35821130 rs35590968 rs35276120 rs34406842 rs34133255 rs12944151 rs2228945
Protein kinase C beta typePRKCB15579KPCB_HUMANrs35631544 rs3729904 rs3729896 rs432998 rs56041613 rs55942437 rs17847891 rs17847884 rs17847879 rs17847876 rs3729895
SEC14-like protein 2SEC14L223541S14L2_HUMANrs757660 rs35984615 rs34425833 rs34330978 rs34215778 rs9608908
SEC14-like protein 3SEC14L3266629S14L3_HUMANrs2269961 rs4820853 rs5749104 rs2240345 rs56111151 rs35764129 rs35149172 rs34559544
SEC14-like protein 4SEC14L4284904S14L4_HUMANrs55650691 rs35032582 rs35013820 rs17738540 rs17738527 rs17670870 rs9608956 rs9606739 rs9606738 rs8138701
Alpha-tocopherol transfer proteinTTPA7274TTPA_HUMANrs35916840 rs34647756 rs34258920 rs28936369 rs17854960 rs13257608
FilesDB00163.mol | DB00163_780.pdf | pdb_9978157024834-0.pdb | sdf_2900902414996-0.sdf |
Smilesisomeric:
CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC[C@]1(C)CCC2=C(O1)C(C)=C(C)C(O)=C2C
canonical:
CC(C)CCCC(C)CCCC(C)CCCC1(C)CCC2=C(O1)C(C)=C(C)C(O)=C2C

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