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1996 Fiscal Year Final Research Report Summary

Molecular Mechanism of Vitamine E recycling in vivo.

Research Project

Project/Area Number 07672346
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionFaculty of Pharmaceutical Sciences, University of Tokyo

Principal Investigator

ARAI Hiroyuki  University of Tokyo, Faculty of Pharmaceutical Sciences, Associate Profesor, 薬学部, 助教授 (40167987)

Project Period (FY) 1995 – 1996
KeywordsVitamine E / alpha-Tocopherol / alpha-Tocopherol transfer protein / Vitamine E deficiency / L-DL / Liver
Research Abstract

Alpha-tocopherol, the most biologcally active form of vitamin E,is a lipid soluble antioxidant that protects membranes from oxidative stresses. Vitamin E occurs in nature in eight different forms, but animal body is enriched in alpha-tocopherol compared with other forms. Studies on the transport vitamin E in animals and man suggest that the liver plays a key role in the preferential retention, and subsequent distribution of alpha-tocopherol to tissues, but little was known about the mechanism. Alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein with highly specific binding ability for alpha-tocopherol. Alpha-TTP also has an ability to transport alpha-tocopherol between membranes in vitro. We have succeeded in purifying this protein from rat liver and isolating its cDNA from rat and human. Furthermore, we have demonstrated that the mutations in the gene that encodes alpha-TTP cause ataxia with familial vitamin E deficiecy. Patients with this disease have low or undetectable serum alpha-tocopherol concentrations and progressive spinocerebellar dysfunction. In these patients, the absorption of alpha-tocopherol from intestine and the transport to the liver is normal, but they have an impaired ability to incorporate alpha-tocopherol into VLDL in the liver. From these observation, it was found that alpha-TTP catalyze the transfer of alpha-tocopherol taken up by the liver into nascent VLDL.

  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 新井 洋由: "ビタミンE輸送タンパク質と先天性ビタミンE欠乏症" 日本油化学会誌. 45. 425-434 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H-S.Kim: "Age-related changes of α-tocopherol transfer protein expression in rat liver." J.Nutr.Sci.Vitamminol.42. 11-18 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Gotoda: "Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the α-tocopherol-transfer protein" The New Eng.J.Med.333. 1313-1318 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Arita: "Human α-tocopherol transfer protein : cDNA cloning,expression and chromosomal localization" Biochem.J.306. 437-443 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Ouahchi: "Ataxia with isolated vitamin E deficiency is caused by mutations in the α-tocopherol transfer protein" Nature Genet.9. 141-145 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Han-Suk Kim: "Age-related changes of alpha-tocopherol transfer protein expression in rat liver" J.Nutr. Sci. Vitaminol.42. 11-18 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takanari Gotoda: "Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein" The New Eng. J.of Med.333. 1313-1318 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makoto Arita: "(Human alpha-tocopherol transfer protein : cDNA cloning, expression and chromosomal localization" Biochem, J.306. 437-443 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Karim Ouahchi: "Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein" Nature Genet.9. 141-145 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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