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1990 Fiscal Year Final Research Report Summary

Studies on the Mechanism of Oxalogenesis and Primary Hyperoxaluria Type 1

Research Project

Project/Area Number 01480153
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

ICHIYAMA Arata  Professor, Department of Biochemistry, Hamamatsu University School of Medicine, 医学部, 教授 (90025601)

Project Period (FY) 1989 – 1990
KeywordsPrimary hyperoxaluria type 1 / Serine : pyruvate aminotransferase / Peroxisomes / Oxalate / Glyoxylate / Thiazolidine-2, 4-dicarboxylate / Human liver serinepyruvate aminotransferase cDNA / 03Diagnostic gene analysis of primary hyperoxaluria type 1
Research Abstract

In this study, I aimed at (1) elucidating the mechanism of oxalogenesis in mammals, and (2) cloning and sequencing the serine : pyruvate aminotransferase (SPT) cDNA and gene from human liver for the gene analysis in the future of primary hyperozaluria type 1 (PH1). Since a patient with PH1 died during the period of this study, SPT-cDNA was also cloned from the patient's liver and the nucleotide sequence was determined.
With respect to the oxalate production in vivo, none of the three enzymes known to catalyze in vitro the oxidation of glyoxylate to oxalate appeared to play substantial role. Instead, oral administration to rat of thiazolidine-2, 4-dicarboxylate, an adduct of glyoxylate with cysteine, was shown to increase slightly the urinary excretion of oxalate. Studies on the possible involvement of thiazolidine-2, 4-dicarboxylate in the oxalate formation from glyoxylate are currently under way. With respect to the genetic defect in the case of PH1, nucleotide sequence analysis of SPT-cDNA from the patient's liver revealed a point mutation of T to C at position 613 (relative to the first nucleotide, A, of the ATG triplet for the initiation Met) encoding a Ser to Pro substitution at residue 205. The T to C conversion created a new SmaI site, which enabled us to demonstrate that the point mutation had occurred in the patient's SPT gene. SmaI digestion of genomic DNA may be useful for the diagnostic gene analysis of this type of PH1. In the liver of this patient, SPT was very low with respect to not only the activity but also the protein detectable on Western blot and immunocytochemical analyses, but the level of SPT-mRNA was found on RNA blot analysis to be even higher than normal, suggesting that the degradation of SPT is accelerated in the patient's liver due to the mutation.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Miyajima,H.,Oda,T.&Ichiyama,A.: "Induction of mitochondrial serin:pyruvate aminotransferase of rat liver by glucagon and insulin through different mechanisms." The Journal of Biochemistry. 105. 500-504 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oda,T.,Miyajima,H.,Suzuki,Y.,Ito,T.,Yokota,S.,Hoshino,M.&Ichiyama,A.: "Purification and characterization of the active serine:pyruvate aminotransferase of rat liver mitochondria expressed in Escherichia coli." The Journal of Biochemistry. 106. 460-467 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oda,T.,Funai,T.&Ichiyama,A.: "Generation from a single gene of two mRNAs that encode the mitochondrial and peroxisomal serine:pyruvate aminotransferase of rat liver." The Journal of Biological Ghemistry. 265. 7513-7519 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagawa,M.,MaedaーNakai,E.,Yamakawa,K.,Yamamoto,I.,Kawamura,J.,Tada,S.&Ichiyama,A.: "The formation of oxalate from glycolate in rat and human liver." Biochimica et Biophysica Acta. 1036. 24-33 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyama,K.,Berstin.G.,Oda,T.&Ichiyma,A.: "Cloning and nucleotide sequence of cDNA encoding human liver serineーpyruvate aminotransferase." European Journal of Biochemistry. 194. 9-18 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokota,S.,Funai,T.&Ichiyama,A.: "Organelle localization of rat liver serine:pyruvate aminotransferase expressed in transfected COSー1 cells." Biomedical Research. 12. 53-59 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishiyama,K.,Funai,T.,Katafuchi,R.,Hattori,F.,Onoyama,K,& Ichivama,A.: "Primary hyperoxaluria type 1 due to a point mutation of T to C in the coding region of the serine:pyruvate aminotransferase gene," Submitted for publication.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yanagawa,M.,MaedaーNakai,E.,Ichiyama,A.,Yamakawa,K.,Yamamoto,I.,Kawamura,J.&Tada,S.: "Urolithiasis (V.R.Walker,R.A.L.Sutton,E.C.B.Cameron,C.Y.C.Pak & W.G.Robertson,eds.) ーー Oxalate synthesizing enzymes in rat liver (pp.421ー423)" Plenum Press,New York and London, 1066 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 市山 新,小田 敏明,船井 恒嘉,西山 孝三: "泌尿器外科第3巻第8号ー分担執筆:原発性高シュウ酸尿症I型(909ー917頁)" 医学図書出版株式会社,東京, 118 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichiyama,A.,Uda,T.,Funai,T.&Nishiyama,K.: "Vitamin B6 and Carbonyl Catalysis (Proceedings of the 8th International Symposium on Vitamin B6 and Carbonyl Catalysis,H.Wada,K.Soda,T.Fukui & H.Kagamiyama,eds) ーー Synthesis and organelle localization of serine:pyruvate aminotransferase in rat & human liver." Pergamon Press,Oxford, (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyajuma, H., Oda, T. & Ichiyama, A.: "Induction of mitochondrial serinepyruvate aminotransferase of rat liver by glucagon and insulin through different mechanisms." The Journal of Biochemistry. Vol. 105. 500-504 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oda, T., Miyajima, H., Suzuki, Y., Ito, T., Yokota, S., Hoshino, M. & Ichiyama, A.: "Purification and characterization of the active serinepyruvate aminotransferase of rat liver mitochondria expressed in Escherichia coli." The Journal of Biochemistry. Vol. 106. 460-467 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagawa, M., Maeda-Nakai, E., Ichiyama, A., Yamakawa, K., Yamamoto, I., Kawamura, J. & Tada, S.: "Oxalate synthesizing enzymes in rat liver." Urolithiasis (V. R. Walker, R. A. L. Sutton, E. C. B. Cameron, C. Y. C. Pak & W. G. Robertson, eds.). 421-423, (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oda, T., Funai, T. & Ichiyama, A.: "Generation from a single gene of two mRNAs that encode the mitochondrial and peroxisomal serine : pyruvate aminotransferase of rat liver." The Journal of Biological Chemistry,. Vol. 265. 7513-7519 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yanagawa, M., Maeda-Nakai, E., Yamakawa, K., Yamamoto, I., Kawamura, J., Tada, S. & Ichiyama, A.: "The formation of oxalate from glycolate in rat and human liver." Biochimica et Biophysica Acta,. Vol. 1036. 24-33 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama, K., Berstein, G., Oda, T. & Ichiyama, A.: "Cloning and nucleotide sequence of cDNA encoding human liver serine-pyruvate aminotransferase." European Journal of Biochemistry. Vol. 194. 9-18 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokota, S., Funai, T. & Ichiyama, A.: "Organelle localization of rat liver serinepyruvate aminotransferase expressed in transfected COS-1 cells." Biomedical Research. Vol. 12. 53-59 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichiyama, A., Oda, T., Funai, T. & Nish yama, K.: "Synthesis and orhanelle localization of serinepyruvate aminotransferase in rat and human liver." Vitamin B6 and Carbonyl Catalysis (Proceedings of the 8th International Symposium on Vitamin B6 and Carbonyl Catalysis, H. Wada, K. Soda, T. Fukui & Kagamiyama, eds.) Pergamon Press, Oxford.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishiyama, K., Funai, T., Katafuchi, R., Hattori, F., Onoyama, K. & Ichiyama, A. :"Primary hyperoxaluria type 1 due to a point mutation of T to C in the coding region of the serinepyruvate aminotransferase gene."

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

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Published: 1993-08-12  

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