Molecular Biology of Catecholamine Systems: Multiple Tyrosine Hydroxylases in Different Simian Species, and in Humans in Relation to Parkinson’s Disease

  • Toshiharu Nagatsu
  • Hiroshi Ichinose
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


The main biochemical characteristics of Parkinson’s disease are the reduction of dopamine the neurotransmitter, and of tyrosine hydroxylase (TH) and the biopterin cofactor, the dopamine-synthesizing enzyme system, in the nigrostriatal dopamine neurons. A deficiency in the dopamine-synthesizing enzymes is accompanied by cell loss of the nigrostriatal dopamine neurons, which is assumed to be caused by unknown exogenous, environmental factors and endogenous, genetic factors. Not only the nigrostriatal dopamine neurons but also other catecholamine neurons may be impaired, as suggested by decreases in dopamine β-hydroxylase (DBH) in norepinephrine neurons and phenylethanolamine Nmethyltransferase (PNMT) in epinephrine neurons (Nagatsu et al., 1977; Nagatsu et al., 1984).


Tyrosine Hydroxylase Splice Site Tyrosine Hydroxylase Gene Norepinephrine Neuron Catecholamine Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Coker III, G. T., Studelska, D., Harmon, S., Burke, W., and O’Malley, K. L., 1990, Analysis of tyrosine hydroxylase and insulin transcript in human neuroendocrine tissues, Mol. Brain Res. 8: 93–98.PubMedCrossRefGoogle Scholar
  2. D’ Mello, S. R., Weisberg, E. P., Stachowiak, M. K., Turzai, L. M., Gioio, A. E., and Kaplan, B. B., 1988, Isolation and nucleotide sequence of a cDNA clone encoding bovine adrenal tyrosine hydroxylase: comparative analysis of tyrosine hydroxylase gene products, J. Neurosci. Res. 19: 440449.Google Scholar
  3. Grima, B., Lamouroux, A., Blanot, F., Biguet, N. F., and Mallet, J., 1985, Complete coding sequence of rat tyrosine hydroxylase mRNA, Proc. Natl. Acad. Sci. USA, 82: 617–621.PubMedCrossRefGoogle Scholar
  4. Grima, B., Lamouroux, A., Boni, C., Julien, J. -F., Javoy-Agid, F., and Mallet, J., 1987, A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics, Nature 326: 707–711.PubMedCrossRefGoogle Scholar
  5. Haycook, J. W., 1993, Multiple forms of tyrosine hydroxylase in human neuroblastoma cells: quantitation with isoform-specific antibodies., J. Neurochem. 60: 493–502.CrossRefGoogle Scholar
  6. Ichikawa, S., Ichinose, H., and Nagatsu, T., 1990, Multiple mRNAs of monkey tyrosine hydroxylase, Biochem. Biophys. Res. Commun. 173: 1331–1336.PubMedCrossRefGoogle Scholar
  7. Ichikawa, S., Sasaoka, T., and Nagatsu, T., 1991, Primary structure of mouse tyrosine hydroxylase deduced from its cDNA, Biochem. Biophys. Res. Commun. 176: 1610–1616.PubMedCrossRefGoogle Scholar
  8. Ichinose, H., Ohye, T., Fujita, K., and Nagatsu, T., 1992, Multiplicity of tyrosine hydroxylase in primates, J. Neurochem. 59, Suppl. S20.Google Scholar
  9. Ichinose, H., Ohye, T., Fujita, K., Yoshida, M., Ueda, S., and Nagatsu, T., 1993, Increased heterogeneity of tyrosine hydroxylase in humans, Biochem. Biophys. Res. Commun. 195: 158–165.PubMedCrossRefGoogle Scholar
  10. Iwata, N., Kobayashi, K., Sasaoka, T., Hidaka, H., and Nagatsu, T., 1992, Structure of the mouse tyrosine hydroxylase gene, Biochem. Biophys. Res. Commun. 182: 348–354.PubMedCrossRefGoogle Scholar
  11. Kaneda, N., Kobayashi, K., Ichinose, H., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., and Nagatsu, T., 1987, Isolation of novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene, Biochem. Biophys. Res. Commun. 146: 971–975.PubMedCrossRefGoogle Scholar
  12. Kobayashi, K., Kaneda, N., Ichinose, H., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., and Nagatsu, T., 1987, Isolation of a full-length cDNA-clone encoding human tyrosine hydroxylase type 3. Nucleic Acids Res. 15: 6733–6733.PubMedCrossRefGoogle Scholar
  13. Kobayashi, K., Kaneda, N., Ichinose, H., Kishi, F., Nakazawa, A., Kurosawa, Y., Fujita, K., and Nagatsu, T., 1988, Structures of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. J. Biochem. 103: 907–912.PubMedGoogle Scholar
  14. Le Bourdelles, B., Boularand, S., Boni, P., Horellou, P., Dumas, S., Grima, B., and Mallet, J., 1988, Analysis of the 5’ region of the human tyrosine hydroxylase gene:combined patterns of exon slicing generate multiple regulated tyrosine hydroxylase isoforms, J. Neurochem. 50: 988–991.PubMedCrossRefGoogle Scholar
  15. Lewis, D. A., Melchitzky, D. S., and Haycock, J. W., 1993, Four isoforms of tyrosine hydroxylase are present in human brain, Neuroscience 54: 477–492.PubMedCrossRefGoogle Scholar
  16. Mogi, M., Harada, M., Kiuchi, K., Kojima, K., Kondo, T., Narabayashi, H., Rausch, D., Riederer, P., Jellinger, K., and Nagatsu, T., 1988, Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain, J. Neural Transm. 72: 77–91.PubMedCrossRefGoogle Scholar
  17. Mogi, M., Harada, M., Kojima, K., Kiuchi, K., Nagatsu, I., and Nagatsu, T., 1987, Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content, Neurosci. Leu. 80: 213–238.CrossRefGoogle Scholar
  18. Nagatsu, T., 1991, Genes for human catecholamine-synthesizing enzymes, Neurosci. Res. 12: 315–345.PubMedCrossRefGoogle Scholar
  19. Nagatsu, T., Kato, T., Numata (Sudo), Y., Ikuta, K., Sano, M., Nagatsu, I., Kondo, Y., Inagaki, S., Iizuka, R.,Hori, A., and Narabayashi, H., 1977, Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain, Clin. Chim. Acta 75: 221–232.PubMedCrossRefGoogle Scholar
  20. Nagatsu, T., Yamaguchi, T., Rahman, M. K., Trocewicz, J., Oka, K., Hirata, Y., Nagatsu, I., Narabayashi, H., Kondo, T., and Iizuka, R., 1984, Catecholamine-related enzymes and the biopterin cofactor in Parkinson’s disci disesme and related extrapyramidal diseases, in: “Advances in Neurology’, R. G. Hassler and J. F. Christ, eds., Raven Press, New York, pp. 463473.Google Scholar
  21. O’ Malley, K. L., Anhalt, M. J., Martin, B. M., Kalsoe, J. R., Winfield, S. L., and Ginns, E. I., 1987, Isolation and characterization of the human tyrosine hydroxylase splice sites responsible for multiple mRNAs, Biochemistry 26: 6910–6914.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Toshiharu Nagatsu
    • 1
  • Hiroshi Ichinose
    • 1
  1. 1.Institute for Comprehensive Medical Science School of MedicineFujita Health UniversityToyoakeJapan

Personalised recommendations