Nutrition
Volume 17, Issue 10 , Pages 799-805 , October 2001

Vitamin e kinetics and the function of tocopherol regulatory proteins

  • David H. Blatt, MD

      Affiliations

    • Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA
    • Oregon Anesthesiology Group, Portland, Oregon, USA
    • ,
  • Scott W. Leonard, MS

      Affiliations

    • Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA
    • ,
  • Maret G. Traber, PhD

      Affiliations

    • Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA
    • Department of Nutrition and Food Management, Oregon State University, Corvallis, Oregon, USA
    • Department of Internal Medicine, University of California–Davis, School of Medicine, Sacramento, California, USA
    • Corresponding Author InformationCorrespondence to: Maret G. Traber, PhD, Linus Pauling Institute, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512, USA

,Accepted 1 June 2001.

References 

  1. In:  Machlin LJ editors. Vitamin E. A comprehensive treatise. New York: Marcel Dekker; 1980;
  2. Machlin LJ, Keating J, Nelson J, et al.  Availability of adipose tissue tocopherol in the guinea-pig. J Nutr. 1979;109:105
  3. Kayden HJ, Hatam LJ, Traber MG. The measurement of nanograms of tocopherol from needle aspiration biopsies of adipose tissue (normal and abetalipoproteinemic subjects). J Lipid Res. 1983;24:652
  4. Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA. Oral α-tocopherol supplements decrease plasma γ-tocopherol levels in humans. J Nutr. 1985;115:807
  5. Baker H, Handelman GJ, Short S, et al.  Comparison of plasma α- and γ-tocopherol levels following chronic oral administration of either all-rac-α-tocopheryl acetate or RRR-α-tocopheryl acetate in normal adult male subjects. Am J Clin Nutr. 1986;43:382
  6. Traber MG, Kayden HJ. Preferential incorporation of α-tocopherol vs γ-tocopherol in human lipoproteins. Am J Clin Nutr. 1989;49:517
  7. Traber MG, Burton GW, Hughes L, et al.  Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism. J Lipid Res. 1992;33:1171
  8. Burton GW, Ingold KU. Autoxidation of biological molecules. I. The antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J Am Chem Soc. 1981;103:6472
  9. Food and Nutrition Board, Institute of Medicine . Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press; 2000;
  10. Ingold KU, Burton GW, Foster DO, et al.  Biokinetics of and discrimination between dietary RRR- and SRR-α-tocopherols in the male rat. Lipids. 1987;22:163
  11. Burton GW, Wronska U, Stone L, Foster DO, Ingold KU. Biokinetics of dietary RRR-α-tocopherol in the male guinea pig at three dietary levels of vitamin C and two levels of vitamin E. Evidence that vitamin C does not “spare” vitamin E in vivo. Lipids. 1990;25:199
  12. Murphy DJ, Mavis RD. Membrane transfer of α-tocopherol. J Biol Chem. 1981;256:10464
  13. Catignani GL. An alpha-tocopherol binding protein in rat liver cytoplasm. Biochem Biophys Res Commun. 1975;67:66
  14. Catignani GL, Bieri JG. Rat liver α-tocopherol binding protein. Biochim Biophys Acta. 1977;497:349
  15. Hosomi A, Goto K, Kondo H, et al.  Localization of α-tocopherol transfer protein in rat brain. Neurosci Lett. 1998;256:159
  16. Copp RP, Wisniewski T, Hentati F, et al.  Localization of α-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders. Brain Res. 1999;822:80
  17. Jishage K, Arita M, Igarashi K, et al.  Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice. J Biol Chem. 2001;273:1669
  18. Hosomi A, Arita M, Sato Y, et al.  Affinity for α-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett. 1997;409:105
  19. Traber MG, Ingold KU, Burton GW, Kayden HJ. Absorption and transport of deuterium-substituted 2R,4′R,8′R-α-tocopherol in human lipoproteins. Lipids. 1988;23:791
  20. Bjørneboe A, Bjørneboe G-EA, Hagen BF, Nossen JO, Drevon CA. Secretion of α-tocopherol from cultured rat hepatocytes. Biochim Biophys Acta. 1987;922:199
  21. Cohn W, Loechleiter F, Weber F. α-Tocopherol is secreted from rat liver in very low density lipoproteins. J Lipid Res. 1988;29:1359
  22. Arita M, Nomura K, Arai H, Inoue K. α-Tocopherol transfer protein stimulates the secretion of α-tocopherol from a cultured liver cell line through a brefeldin A–insensitive pathway. Proc Natl Acad Sci USA. 1997;94:12437
  23. Stocker A, Zimmer S, Spycher SE, Azzi A. Identification of a novel cytosolic tocopherol-binding protein (structure, specificity, and tissue distribution). IUBMB Life. 1999;48:49
  24. Zimmer S, Stocker A, Sarbolouki MN, et al.  A novel human tocopherol-associated protein (cloning, in-vitro expression and characterization). J Biol Chem. 2000;275:25672
  25. Shibata N, Arita M, Misaki Y, et al.  Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis. Proc Natl Acad Sci USA. 2001;98:2244
  26. Dutta-Roy AK, Leishman DJ, Gordon MJ, Campbell FM, Duthie GG. Identification of a low molecular mass (14.2 kDa) α-tocopherol-binding protein in the cytosol of rat liver and heart. Biochem Biophys Res Commun. 1993;196:1108
  27. Dutta-Roy A, Gordon M, Leishman D, et al.  Purification and partial characterisation of an alpha-tocopherol-binding protein from rabbit heart cytosol. Mol Cell Biochem. 1993;123:139
  28. Gordon MJ, Campbell FM, Duthie GG, Dutta-Roy AK. Characterization of a novel alpha-tocopherol–binding protein from bovine heart cytosol. Arch Biochem Biophys. 1995;318:140
  29. Gordon MJ, Campbell FM, Dutta-Roy AK. Alpha-tocopherol-binding protein in the cytosol of the human placenta. Biochem Soc Trans. 1996;24:202S
  30. Shaw H, Huang C. Liver α-tocopherol transfer protein and its mRNA are differentially altered by dietary vitamin E deficiency and protein insufficiency in rats. J Nutr. 1998;128:2348
  31. Fechner H, Schlame M, Guthmann F, Stevens PA, Rustow B. Alpha- and delta-tocopherol induce expression of hepatic alpha-tocopherol-transfer-protein mRNA. Biochem J. 1998;331:577
  32. Kim HS, Arai H, Arita M, et al.  Effect of α-tocopherol status on α-tocopherol transfer protein expression and its mRNA level in rat liver. Free Radic Res. 1998;28:87
  33. Kalra V, Grover J, Ahuja GK, Rathi S, Khurana DS. Vitamin E deficiency and associated neurological deficits in children with protein-energy malnutrition. J Trop Pediatr. 1998;44:291
  34. Tamai H, Kim HS, Hozumi M, et al.  Plasma α-tocopherol in diabetes mellitus. Biofactors. 2000;11:7
  35. Emerson OH, Emerson GA, Mohammed A, Evans HM. The chemistry of vitamin E. Tocopherols from various sources. J Biol Chem. 1937;122:99
  36. Bieri JG, Evarts RP. γ-Tocopherol (metabolism, biological activity and significance in human nutrition). Am J Clin Nutr. 1974;27:980
  37. Baker H, Handelman GJ, Short S, et al.  Comparison of plasma α- and γ-tocopherol levels following chronic oral administration of either all-rac-α-tocopheryl acetate or RRR-α-tocopheryl acetate in normal adult male subjects. Am J Clin Nutr. 1986;43:382
  38. Traber MG, Burton GW, Ingold KU, Kayden HJ. RRR- and SRR-α-tocopherols are secreted without discrimination in human chylomicrons, but RRR-α-tocopherol is preferentially secreted in very low density lipoproteins. J Lipid Res. 1990;31:675
  39. Traber MG, Rudel LL, Burton GW, et al.  Nascent VLDL from liver perfusions of cynomolgus monkeys are preferentially enriched in RRR- compared with SRR-α tocopherol (studies using deuterated tocopherols). J Lipid Res. 1990;31:687
  40. Burton GW, Traber MG, Acuff RV, et al.  Human plasma and tissue α-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am J Clin Nutr. 1998;67:669
  41. Kiyose C, Muramatsu R, Kameyama Y, Ueda T, Igarashi O. Biodiscrimination of α-tocopherol stereoisomers in humans after oral administration. Am J Clin Nutr. 1997;65:785
  42. Weiser H, Riss G, Kormann AW. Biodiscrimination of the eight α-tocopherol stereoisomers results in preferential accumulation of the four 2R forms in tissues and plasma of rats. J Nutr. 1996;126:2539
  43. Leonard SW, Terasawa Y, Farese RV, Traber MG. Incorporation of deuterium labeled RRR- and all rac α-tocopherols into plasma and tissues of α-tocopherol transfer protein deficient mice. Am J Clin Nutr 2001(in press)
  44. Lauridsen C, Engel H, Craig AM, Traber MG. Relative bioavailability of dietary RRR- and all-rac-alpha-tocopheryl acetates in swine assessed using deuterium-labeled vitamin E. J Anim Sci 2001(in press)
  45. Traber MG, Ramakrishnan R, Kayden HJ. Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-α-tocopherol. Proc Natl Acad Sci USA. 1994;91:10005
  46. Sokol RJ, Kayden HJ, Bettis DB, et al.  Isolated vitamin E deficiency in the absence of fat malabsorption—familial and sporadic cases (characterization and investigation of causes). J Lab Clin Med. 1988;111:548
  47. Traber MG, Sokol RJ, Burton GW, et al.  Impaired ability of patients with familial isolated vitamin E deficiency to incorporate α-tocopherol into lipoproteins secreted by the liver. J Clin Invest. 1990;85:397
  48. Cavalier L, Ouahchi K, Kayden HJ, et al.  Ataxia with isolated vitamin E deficiency (heterogeneity of mutations and phenotypic variability in a large number of families). Am J Hum Genet. 1998;62:301
  49. Terasawa Y, Ladha Z, Leonard SW, et al.  Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E. Proc Natl Acad Sci USA. 2000;97:13830
  50. Traber MG. Vitamin E. In: Shils ME, Olson JA, Shike M, and Ross AC, eds. Modern nutrition in health and disease, 9th ed. Baltimore: Williams & Wilkins, 1999:347
  51. Traber MG, Rader D, Acuff R, et al.  Vitamin E dose response studies in humans with use of deuterated RRR-α-tocopherol. Am J Clin Nutr. 1998;68:847
  52. Traber MG, Kayden HJ, Green JB, Green MH. Absorption of water-miscible forms of vitamin E in a patient with cholestasis and in thoracic duct-cannulated rats. Am J Clin Nutr. 1986;44:914
  53. Stahl W, Graf P, Brigelius-Flohe R, Wechter W, Sies H. Quantification of the α- and γ-tocopherol metabolites 2,5,7,8-tetramethyl-2-(2′-carboxyethyl)-6-hydroxychroman and 2,7,8-trimethyl-2-(2′-carboxyethyl)-6-hydroxychroman in human serum. Anal Biochem. 1999;275:254
  54. Machlin LJ, Gabriel E. Kinetics of tissue α-tocopherol uptake and depletion following administration of high levels of vitamin E. Ann NY Acad Sci. 1982;393:48
  55. Schuelke M, Elsner A, Finckh B, et al.  Urinary α-tocopherol metabolites in α-tocopherol transfer protein-deficient patients. J Lipid Res. 2000;41:1543
  56. Schultz M, Leist M, Petrzika M, Gassmann B, Brigelius-Flohé R. Novel urinary metabolite of alpha-tocopherol, 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply?. Am J Clin Nutr. 1995;62(suppl)::1527S
  57. Bourre J, Clement M. Kinetics of rat peripheral nerve, forebrain and cerebellum α-tocopherol depletion (comparison with different organs). J Nutr. 1991;121:1204
  58. Vatassery GT, Brin MF, Fahn S, Kayden HJ, Traber MG. Effect of high doses of dietary vitamin E on the concentrations of vitamin E in several brain regions, plasma, liver, and adipose tissue of rats. J Neurochem. 1988;51:621
  59. Horwitt MK, Harvey CC, Duncan GD, Wilson WC. Effects of limited tocopherol intake in man with relationships to erythrocyte hemolysis and lipid oxidations. Am J Clin Nutr. 1956;4:408
  60. Harding AE, Muller DP, Thomas PK, Willison HJ. Spinocerebellar degeneration secondary to chronic intestinal malabsorption (a vitamin E deficiency syndrome). Ann Neurol. 1982;12:419
  61. Bessesen DH, Richards CL, Etienne J, Goers JW, Eckel RH. Spinal cord of the rat contains more lipoprotein lipase than other brain regions. J Lipid Res. 1993;34:229
  62. Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science. 1922;56:650
  63. Kaempf, D.; Miki, M.; Ogihara, T.; et al. Assessment of vitamin E nutritional status in neonates, infants and children—on the basis of alpha-tocopherol levels in blood components and buccal mucosal cells. Int J Vitam Nutr Res 1994:64.
  64. Acuff RV, Dunworth RG, Webb LW, Lane JR. Transport of deuterium-labeled tocopherols during pregnancy. Am J Clin Nutr. 1998;67:459
  65. Terasawa Y, Cases SJ, Wong JS, et al.  Apolipoprotein B-related gene expression and ultrastructural characteristics of lipoprotein secretion in mouse yolk sac during embryonic development. J Lipid Res. 1999;40:1967
  66. Rindler M, Traber MG, Esterman A, Bersinger N, Dancis J. Synthesis and secretion of apolipoprotein E by human placenta and choriocarcinoma cell lines. Placenta. 1991;12:615
  67. Kiely M, Cogan PF, Kearney PJ, Morrissey PA. Concentrations of tocopherols and carotenoids in maternal and cord blood plasma. Eur J Clin Nutr. 1999;53:711
  68. Qanungo S, Mukherjea M. Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol Cell Biochem. 2000;215:11
  69. Tran K Chan AC. Comparative uptake of α- and γ-tocopherol by human endothelial cells. Lipids. 1992;27:38
  70. Swanson JE, Ben RN, Burton GW, Parker RS. Urinary excretion of 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman is a major route of elimination of γ-tocopherol in humans. J Lipid Res. 1999;40:665
  71. Lodge JK, Riddlington J, Vaule H, Leonard SW, Traber MG. α- and γ-Tocotrienols are metabolized to carboxyethyl-hydroxychroman (CEHC) derivatives and excreted in human urine. Lipids. 2001;36:43
  72. Clement M, Bourre J-M. Graded dietary levels of RRR-γ-tocopherol induce a marked increase in the concentrations of α- and γ-tocopherol in nervous tissues, heart, liver and muscle of vitamin E deficient rats. Biochim Biophys Acta. 1997;1334:173
  73. Saldeen T, Li D, Mehta JL. Differential effects of α- and γ-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol. 1999;34:1208
  74. Parker RS, Sontag TJ, Swanson JE. Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem Biophys Res Commun. 2000;277:531
  75. Yamashita K, Nohara Y, Katayama K, Namiki M. Sesame seed lignans and gamma-tocopherol act synergistically to produce vitamin E activity in rats. J Nutr. 1992;122:2440
  76. Yamashita K, Iizuka Y, Imai T, Namiki M. Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low alpha-tocopherol diet. Lipids. 1995;30:1019
  77. Kamal-Eldin A, Petterson D, Appelqvist LA. Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids. 1995;30:499
  78. Traber MG, Kayden HJ. Tocopherol distribution and intracellular localization in human adipose tissue. Am J Clin Nutr. 1987;46:488
  79. Handelman GJ, Epstein WL, Peerson J, Spiegelman D, Machlin LJ. Human adipose α-tocopherol and γ-tocopherol kinetics during and after 1 y of α-tocopherol supplementation. Am J Clin Nutr. 1994;59:1025
  80. Traber MG, Sokol RJ, Ringel SP, et al.  Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy. N Engl J Med. 1987;317:262
  81. Pillai SR, Traber MG, Steiss JE, Kayden HJ. Depletion of adipose tissue and peripheral nerve α-tocopherol in adult dogs. Lipids. 1993;28:1095
  82. Steiss JE, Traber MG, Williams MA, Kayden HJ, Wright JC. Vitamin E status in clinically normal adult horses (Alpha tocopherol concentrations in plasma and adipose tissue). Equine Vet J. 1994;26:417
  83. Buttriss JL, Diplock AT. The relationship between α-tocopherol and phospholipid fatty acids in rat liver subcellular membrane fractions. Biochim Biophys Acta. 1988;962:81
  84. Hao M, Maxfield FR. Characterization of rapid membrane internalization and recycling. J Biol Chem. 2000;275:15279
  85. Mayor S, Presley JF, Maxfield FR. Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. J Cell Biol. 1993;121:1257
  86. Traber MG, Olivecrona T, Kayden HJ. Bovine milk lipoprotein lipase transfers tocopherol to human fibroblasts during triglyceride hydrolysis in vitro. J Clin Invest. 1985;75:1729
  87. Kostner GM, Oettl K, Jauhiainen M, et al.  Human plasma phospholipid transfer protein accelerates exchange/transfer of α-tocopherol between lipoproteins and cells. Biochem J. 1995;305:659
  88. Asmis R. Physical partitioning is the main mechanism of α-tocopherol and cholesterol transfer between lipoproteins and P388D1 macrophage-like cells. Eur J Biochem. 1997;250:600
  89. Cheng SC, Burton GW, Ingold KU, Foster DO. Chiral discrimination in the exchange of alpha-tocopherol stereoisomers between plasma and red blood cells. Lipids. 1987;22:469
  90. Nakamura T, Reicher H, Sattler W. Comparison of RRR-α- and all-rac-α-tocopherol uptake by permanent rat skeletal muscle myoblasts (L6 cells) (effects of exogenous lipoprotein lipase). Lipids. 1998;33:1001
  91. Goti D, Hammer A, Galla HJ, Malle E, Sattler W. Uptake of lipoprotein-associated α-tocopherol by primary porcine brain capillary endothelial cells. J Neurochem. 2000;74:1374
  92. Goti D, Reicher H, Malle E, et al.  High-density lipoprotein (HDL3)-associated alpha-tocopherol is taken up by HepG2 cells via the selective uptake pathway and resecreted with endogenously synthesized apo-lipoprotein B-rich lipoprotein particles. Biochem J. 1998;332:57
  93. Traber MG, Kayden HJ. Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr. 1984;40:747
  94. Kolleck I, Schlame M, Fechner H, et al.  HDL is the major source of vitamin E for type II pneumocytes. Free Radic Biol Med. 1999;27:882

PII: S0899-9007(01)00637-2

Nutrition
Volume 17, Issue 10 , Pages 799-805 , October 2001

Article Tools