Molecular Basis of DOPA-Responsive Dystonia

  • Chiho Sumi-Ichinose
  • Fumi Urano
  • Masayo Kojima
  • Risa Kuroda
  • Hiroaki Shiraishi
  • Yasumichi Hagino
  • Toshiharu Nagatsu
  • Takahide Nomura
  • Hiroshi Ichinose

Abstract

Biosynthesis of catecholamines and serotonin is mainly regulated by the activity of the hydroxylation reaction catalyzed by tyrosine hydroxylase (TH) in catecholamine synthesis and by tryptophan hydroxylase (TPH) in 5HT-synthesis. 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for both TH and TPH. BH4 is synthesized from guanosine triphosphate (GTP) through three enzymatic reactions catalyzed by GTP cyclohydrolase I (GCH), pyruvoyltetrahydropterin synthase (PTS), and sepiapterin reductase. GCH is a rate-limiting enzyme for the de novo synthesis of BH4.

Keywords

Dopamine Leukemia Serotonin Folate Norepinephrine 

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References

  1. 1.
    Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K. and Nagatsu, T., Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nature Genet 8: 236–242, 1994.PubMedCrossRefGoogle Scholar
  2. 2.
    Sumi-Ichinose, C., Urano, F., Kuroda, R., Ohye, T., Kojima, M, Tazawa, M, Shiraishi, H., Hagino, Y., Nagatsu, T., Nomura, T., and Ichinose, H. Catecholamines and serotonin are differently regulated by tetrahydrobiopterin: a study from 6-pyruvoyltetrahydropterin synthase knockout mice. J Biol Chem. in press, 2001.Google Scholar
  3. 3.
    Schoedon, G., Troppmair, J., Fontana, A., Huber, C., Curtius, H.C. and Niederwieser, A. Biosynthesis and metabolism of pterins in peripheral blood mononuclear cells and leukemia lines of man and mouse. Eur J Biochem 166: 303–310, 1987.PubMedCrossRefGoogle Scholar
  4. 4.
    Werner, E.R., Werner-Felmayer, G., Fuchs, D., Hausen, A., Reibnegger, G., Yim, J.J. and Wachter, H. Impact of tumour necrosis factor-α and interferon-γ on tetrahydrobiopterin synthesis in murine fibroblasts and macrophages. Biochem J 280: 709–714, 1991.PubMedGoogle Scholar
  5. 5.
    Rajput, A.H., Gibb, W.R., Zhong, X.H., Shannak, K.S., Kish, S., Chang, L.G. and Hornykiewicz, O. Dopa-responsive dystonia: pathological and biochemical observations in a case. Ann Neurol 35: 396–402, 1994.PubMedCrossRefGoogle Scholar
  6. 6.
    Furukawa, Y., Nygaard, T.G., Gutlich, M., Rajput, A.H., Pifl, C., DiStefano, L., Chang, L.J., Price, K., Shimadzu, M, Hornykiewicz, O., Haycock, J.W. and Kish, S.J., Striatal biopterin and tyrosine hydroxylase protein reduction in dopa-responsive dystonia. Neurol 53: 1032–1041, 1999.CrossRefGoogle Scholar
  7. 7.
    Klatt, P., Schmid, M., Leopold, E., Schmidt, K., Werner, E.R. and Mayer, B., The pteridine binding site of brain nitric oxide synthase. Tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain. J Biol Chem 269: 13861–13866, 1994.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Chiho Sumi-Ichinose
    • 1
  • Fumi Urano
    • 2
  • Masayo Kojima
    • 2
  • Risa Kuroda
    • 1
  • Hiroaki Shiraishi
    • 1
  • Yasumichi Hagino
    • 1
  • Toshiharu Nagatsu
    • 2
  • Takahide Nomura
    • 1
  • Hiroshi Ichinose
    • 2
  1. 1.Department of PharmacologyFujita Health University School of MedicineToyoake, AichiJapan
  2. 2.Institute for Comprehensive Medical ScienceFujita Health UniversityToyoake, AichiJapan

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