title: Vitamin E trafficking in neurologic health and disease.
abstract: Vitamin E was identified almost a century ago as a botanical compound necessary for rodent reproduction. Decades of research since then established that of all members of the vitamin E family, α-tocopherol is selectively enriched in human tissues, and it is essential for human health. The major function of α-tocopherol is thought to be that of a lipid-soluble antioxidant that prevents oxidative damage to biological components. As such, α-tocopherol is necessary for numerous physiological processes such as permeability of lipid bilayers, cell adhesion, and gene expression. Inadequate levels of α-tocopherol interfere with cellular function and precipitate diseases, notably ones that affect the central nervous system. The extreme hydrophobicity of α-tocopherol poses a serious thermodynamic barrier for proper distribution of the vitamin to target tissues and cells. Although transport of the vitamin shares some steps with that of other lipids, selected tissues evolved dedicated transport mechanisms involving the α-tocopherol transfer protein (αTTP). The critical roles of this protein and its ligand are underscored by the debilitating pathologies that characterize human carriers of mutations in the TTPA gene.
authors: Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Lynn
authors: L
authors: Ulatowski
authors: Danny
authors: D
authors: Manor
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D002493:Central Nervous System Diseases / Q000209:etiology*; D006801:Humans; D014810:Vitamin E / Q000378:metabolism* / Q000627:therapeutic use; D014811:Vitamin E Deficiency / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E
references: N Engl J Med. 1995 Nov 16;333(20):1313-8
references: 7566022
references: Proc Soc Exp Biol Med. 1988 Oct;189(1):52-60
references: 3186764
references: Ann Intern Med. 1987 Jul;107(1):51-4
references: 3592448
references: Biochemistry. 2004 Apr 13;43(14):4143-9
references: 15065857
references: Bioorg Med Chem Lett. 2012 Jan 1;22(1):391-5
references: 22137789
references: J Biol Chem. 2008 Mar 14;283(11):6915-24
references: 18180306
references: Curr Opin Lipidol. 2002 Aug;13(4):373-81
references: 12151852
references: Nature. 1979 Apr 19;278(5706):737-8
references: 431730
references: J Nutr. 2011 Oct;141(10):1847-54
references: 21865568
references: Biochim Biophys Acta. 2007 Jul;1772(7):797-803
references: 17560088
references: N Engl J Med. 1993 May 20;328(20):1444-9
references: 8479463
references: J Inherit Metab Dis. 1985;8 Suppl 1:88-92
references: 3930848
references: J Nutr Biochem. 2010 Jan;21(1):66-76
references: 19157826
references: Biochim Biophys Acta. 2012 Feb;1822(2):150-60
references: 22120593
references: J Neurol Sci. 1990 Dec;100(1-2):79-84
references: 2089143
references: Vitam Horm. 2007;76:45-65
references: 17628171
references: Biochim Biophys Acta. 1995 May 17;1256(2):175-80
references: 7766695
references: Curr Med Chem. 2004 May;11(9):1113-33
references: 15134510
references: Lancet. 1996 Mar 23;347(9004):781-6
references: 8622332
references: J Lipid Res. 1993 Feb;34(2):201-10
references: 8429255
references: J Neural Transm (Vienna). 2000;107(4):393-407
references: 11215751
references: Genes Nutr. 2012 Jan;7(1):1
references: 21590364
references: J Mol Biol. 2011 Jan 28;405(4):972-88
references: 21110980
references: J Cell Mol Med. 2009 Sep;13(9B):3786-96
references: 18774957
references: Lancet. 1982 Aug 7;2(8293):327
references: 6124736
references: Biochem Biophys Res Commun. 1975 Nov 3;67(1):66-72
references: 1201037
references: Annu Rev Biochem. 1947;16:177-92
references: 20259061
references: J Alzheimers Dis. 2010;20(4):1029-37
references: 20413888
references: J Neurol Sci. 1994 May;123(1-2):64-73
references: 8064324
references: Ann Nutr Metab. 2006;50(5):433-41
references: 16847396
references: J Nutr. 1991 Aug;121(8):1204-7
references: 1861168
references: J Neurochem. 2004 May;89(4):939-50
references: 15140193
references: Bioinformatics. 2006 Mar 1;22(5):623-5
references: 16397007
references: J Lipid Res. 1993 Mar;34(3):343-58
references: 8468520
references: Toxicol Pathol. 1984;12(3):235-9
references: 6515277
references: Protein Expr Purif. 1993 Oct;4(5):382-9
references: 8251749
references: Biochim Biophys Acta. 2010 Aug;1801(8):806-18
references: 20170744
references: Mol Vis. 2013;19:231-42
references: 23401652
references: J Lab Clin Med. 1988 May;111(5):548-59
references: 3361234
references: Mol Nutr Food Res. 2010 May;54(5):693-709
references: 20187127
references: Pediatrics. 2004 Jun;113(6):1549-58
references: 15173473
references: Biochemistry. 2006 Jul 11;45(27):8236-42
references: 16819822
references: J Lipid Res. 1996 Apr;37(4):893-901
references: 8732789
references: J Neurosci Res. 2006 Nov 1;84(6):1335-42
references: 16941498
references: Clin Sci (Lond). 2007 Dec;113(12):459-66
references: 17576196
references: Am J Clin Nutr. 2002 Mar;75(3):555-60
references: 11864863
references: J Biol Chem. 2001 Oct 26;276(43):39898-902
references: 11546785
references: Lipids. 1987 Mar;22(3):163-72
references: 3573996
references: Brain Res. 1999 Mar 20;822(1-2):80-7
references: 10082886
references: Ann Intern Med. 2005 Jul 19;143(2):152; author reply 156-8
references: 16027464
references: Am J Epidemiol. 1999 Aug 1;150(3):290-300
references: 10430234
references: Free Radic Biol Med. 2008 Mar 1;44(5):739-64
references: 18160049
references: Curr Opin Lipidol. 2003 Jun;14(3):249-54
references: 12840655
references: J Biol Chem. 2001 Jan 19;276(3):1669-72
references: 11076932
references: J Nutr. 2002 Mar;132(3):443-9
references: 11880569
references: J Thorac Cardiovasc Surg. 1994 Aug;108(2):302-10
references: 8041178
references: Lancet. 1983 Jan 29;1(8318):225-8
references: 6130255
references: FEBS Lett. 1991 Aug 19;288(1-2):41-5
references: 1879562
references: Free Radic Biol Med. 2012 Dec 15;53(12):2318-26
references: 23079030
references: Traffic. 2010 Apr;11(4):419-28
references: 20059748
references: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13830-4
references: 11095717
references: Free Radic Biol Med. 1999 Aug;27(3-4):334-46
references: 10468207
references: Biol Reprod. 2005 Nov;73(5):983-7
references: 16014812
references: J Nutr. 1984 Sep;114(9):1588-93
references: 6332184
references: Biochim Biophys Acta. 2010 Aug;1801(8):819-23
references: 20470897
references: J Comp Neurol. 2001 May 7;433(3):415-25
references: 11298365
references: Neurosci Lett. 1998 Nov 13;256(3):159-62
references: 9855364
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12437-41
references: 9356467
references: J Lipid Res. 1992 Aug;33(8):1171-82
references: 1431596
references: J Nutr Biochem. 2010 May;21(5):451-6
references: 19427182
references: Free Radic Biol Med. 2003 Dec 1;35(11):1343-54
references: 14642382
references: J Neural Transm (Vienna). 1997;104(6-7):703-10
references: 9444569
references: J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):521-5
references: 10727494
references: J Biol Chem. 1993 Aug 25;268(24):17705-10
references: 8349655
references: Lancet Neurol. 2005 Jun;4(6):362-5
references: 15907740
references: Ciba Found Symp. 1983;101:4-18
references: 6557906
references: J Neurochem. 2000 Apr;74(4):1374-83
references: 10737592
references: Adv Pediatr. 1990;37:119-48
references: 2176058
references: Nat Genet. 1995 Feb;9(2):141-5
references: 7719340
references: Cancer Res. 2009 Feb 15;69(4):1429-38
references: 19190344
references: Annu Rev Nutr. 1990;10:357-82
references: 2200468
references: Free Radic Res Commun. 1990;11(1-3):99-107
references: 2074052
references: Brain. 1991 Apr;114 ( Pt 2):915-36
references: 1710528
references: J Biol Chem. 2008 Jun 27;283(26):17797-804
references: 18458085
references: Biochem J. 1995 Mar 1;306 ( Pt 2):437-43
references: 7887897
references: Biochim Biophys Acta. 1987 Nov 21;922(2):199-205
references: 2823906
references: Mol Nutr Food Res. 2010 May;54(5):710-8
references: 20183831
references: Annu Rev Nutr. 1988;8:351-73
references: 3060170
references: Biochim Biophys Acta. 1977 Apr 27;497(2):349-57
references: 870071
references: J Appl Genet. 2004;45(4):461-7
references: 15523158
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15185-90
references: 11752462
references: J Neurol Neurosurg Psychiatry. 1988 Mar;51(3):432-5
references: 2834520
references: Neurol Sci. 2010 Aug;31(4):511-5
references: 20464573
references: Free Radic Biol Med. 2007 Jul 1;43(1):4-15
references: 17561088
references: Cell Mol Life Sci. 2003 Jun;60(6):1158-71
references: 12861382
references: J Neurochem. 1984 Aug;43(2):409-12
references: 6736958
references: Science. 1922 Dec 8;56(1458):650-1
references: 17838496
references: Am J Hum Genet. 1998 Feb;62(2):301-10
references: 9463307
references: Acta Neuropathol. 1993;85(2):175-84
references: 8382896
references: Annu Rev Nutr. 1999;19:343-55
references: 10448528
references: Mol Nutr Food Res. 2010 May;54(5):641-51
references: 20166146
references: J Biol Chem. 2002 Jul 12;277(28):25290-6
references: 11997390
references: J Nutr Sci Vitaminol (Tokyo). 1993;39 Suppl:S9-22
references: 8164071
references: J Anat. 1993 Dec;183 ( Pt 3):451-61
references: 8300427
references: J Lipid Res. 2011 Jul;52(7):1400-10
references: 21550990
references: J Lipid Res. 2005 Oct;46(10):2072-82
references: 16024914