Skip to main content
SpringerLink
Log in

Tyrosine hydroxylase in relation to Parkinson’s disease: a historical overview and future prospect

  • Conference paper
Parkinson’s Disease. From Clinical Aspects to Molecular Basis

Part of the book series: Key Topics in Brain Research ((KEYTOPICS))

  • 98 Accesses

Summary

Reduction in tyrosine hydroxylase (TH), the regulatory enzyme for dopamine (DA) biosynthesis, in the nigrostriatal DA region is a characteristic change in Parkinson’s disease. TH was discovered in 1964 as the first and regulatory enzyme in DA biosynthesis, and the specific decrease of TH activity in the nigrostriatal DA region of parkinsonian brains was established around 1975. It has been generally assumed that the decrease in TH activity in parkinsonian brain is due to a reduction in TH protein as a result of cell death of the nigrostriatal DA neurons by unidentified mechanisms. In fact, we found TH activity and TH protein to be decreased in parallel in parkinsonian brain. However, since the discovery of multiple forms of human TH in 1987, some molecular changes in TH protein in Parkinson’s disease are speculated. This speculation may be supported by the increase in homospecific activity (enzyme activity/enzyme protein) of residual TH in parkinsonian brain, in contrast to constant homospecific activity of TH in the striatum of parkinsonian mice treated with l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A molecular biology approach to TH in Parkinson’s disease is expected to reveal the molecular pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bernheimer H, Birkmayer W, Hornykiewcz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20: 415–455

    Google Scholar 

  • Brenneman AR, Kaufman S (1964) The role of tetrahydropteridine in the enzymatic conversion of tyrosine to 3,4-dihydroxyphenylalanine. Biochem Biophys Res Commun 17: 177–183

    Article  CAS  Google Scholar 

  • Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopamine neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l,2,3,6-tetrahydro- pyridine. Proc Natl Acad Sci USA 80: 4546–4550

    Article  PubMed  CAS  Google Scholar 

  • Campbell DG, Hardie DG, Vulliet PR (1986) Identification of four phosphorylation sites in the N-terminal region of tyrosine hydroxylase. J Biol Chem 261: 10489–10492

    PubMed  CAS  Google Scholar 

  • Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1: 249–254

    Article  PubMed  CAS  Google Scholar 

  • Elsworth JD, Deutch AY, Redmond Jr DE, Sladek Jr JR, Roth RH (1987) Effects of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine ( MPTP) on catecholamines and metabolites in primate brain and CSF. Brain Res 415: 293–299

    Google Scholar 

  • Grima B, Lamouroux A, Boni C, Julien JF, Javoy-Agid F, Mallet J (1987) A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature 326: 707–711

    Article  PubMed  CAS  Google Scholar 

  • Heikkila RE, Hess A, Duvoisin RC (1984) Dopaminergic neurotoxicity of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in mice. Science 224: 1451–1453

    Article  PubMed  CAS  Google Scholar 

  • Hirata Y, Nagatsu T (1986) Early and late effects of systematically administered l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine ( MPTP) on tyrosine hydroxylase activity in vitro and on tyrosine hydroxylation in tissue slices of mouse striatum. Neurosci Lett 68: 245–248

    Google Scholar 

  • Ichikawa S, Ichinose H, Nagatsu T (1990) Multiple mRNAs of monkeys tyrosine hydroxylase. Biochem Biophys Res Commun 173: 1331–1336

    Article  PubMed  CAS  Google Scholar 

  • Ishii A, Kiuchi K, Matsuyama M, Satake T, Nagatsu T (1990) Ferrous ion activates the less active form of human adrenal tyrosine hydroxylase. Neurochem Int 16: 59–64

    Article  PubMed  CAS  Google Scholar 

  • Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakasawa A, Kurosawa Y, Fujita K, 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

    Article  PubMed  CAS  Google Scholar 

  • Kaneda N, Kobayashi K, Ichinose H, Sasaoka T, Ishii A, Kiuchi K, Kurosawa Y, Fujita K, Nagatsu T (1990) Molecular biological approaches to catecholamine neurotransmitters and brain aging. In: Nagatsu T, Hayaishi O (eds) Aging of the brain: cellular and molecular aspects of brain aging and Alzheimer’s disease. Japan Scientific Societies Press, Tokyo, and Karger, Basel, pp 53–66

    Google Scholar 

  • Kiuchi K, Hagihara M, Hidaka H, Nagatsu T (1988) Effect of l-methyl-4-phenylpyri-dinium ion on tyrosine hydroxylase in rat pheochromocytoma PC 12h cells. Neurosci Lett 89: 209–215

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1987) Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3-Nucl Acids Res 15: 6733

    CAS  Google Scholar 

  • Kobayashi K, Kaneda N, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1988a) Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. J Biochem 103: 907–912

    PubMed  CAS  Google Scholar 

  • Kobayashi K, Kiuchi K, Ishii A, Kaneda N, Kurosawa Y, Fujita K, Nagatsu T (1988b) Expression of four types of human tyrosine hydroxylase in COS cells. FEBS Lett 238: 431–434

    Article  PubMed  CAS  Google Scholar 

  • Kojima K, Mogi M, Oka K, Nagatsu T (1984) Purification and immunochemical characterization of human adrenal tyrosine hydroxylase. Neurochem Int 6: 475–480

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to product of meperidine-analog synthesis. Science 219: 979–980

    Article  PubMed  CAS  Google Scholar 

  • Ledley FD, DiLella AG, Kwok SCM, Woo SLC (1985) Homology between phenylalanine and tyrosine hydroxylase reveals common structural and functional domains. Biochemistry 24: 3389–3394

    Article  PubMed  CAS  Google Scholar 

  • Levitt M, Spector S, Sjoerdsma A, Udenfriend S (1965) Elucidation of the rate-limiting step in norepinephrine biosynthesis in the perfused guinea-pig heart. J Pharmacol Exp Ther 148: 1–8

    PubMed  CAS  Google Scholar 

  • Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson’s disease: effect of L-DOPA therapy. J Pharmacol Exp Ther 195: 453–464

    PubMed  CAS  Google Scholar 

  • Matsuura S, Sugimoto T, Murata S, Sugawara Y, Iwasaki H (1985) Stereochemistry of biopterin cofactor and facile methods for the determination of the stereochemistry of a biologically active 5,6,7,8-tetrahydropterin. J Biochem 98: 1341–1348

    PubMed  CAS  Google Scholar 

  • McGeer PL, McGeer EG (1976) Enzymes associated with the metabolism of catecholamine, acetylcholine and GABA in human controls and patents with Parkinson’s disease. J Neurochem 26: 65–76

    PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Kojima K, Kiuchi K, Nagatsu I, Nagatsu T (1987) Effects of repeated systemic administration of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine ( MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content. Neurosci Lett 80: 213–218

    Google Scholar 

  • Mogi M, Harada M, Kojima K, Kiuchi K, Nagatsu T (1988a) Effects of systemic administration of l-methyl-4-phenyl-l,2,3,6,-tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus. J Neurochem 50: 1053–1056

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Kiuchi K, Kojima K, Kondo T, Narabayashi H, Rausch D, Riederer P, Jellinger K, Nagatsu T (1988b) Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain. J Neural Transm 72: 77–81

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Kojima K, Harada M, Nagatsu T (1986) Purification and immunological properties of tyrosine hydroxylase in human brain. Neurochem Int 8: 423–428

    Article  PubMed  CAS  Google Scholar 

  • Mogi M, Kojima K, Nagatsu T (1984) Detection of inactive or less active forms of tyrosine hydroxylase in human brain and adrenals by a sandwich enzyme immunoassay. Anal Biochem 138: 125–132

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T (1975) Biosynthesis and metabolism of dopamine (in Japanese). No-to-Shinkei (Brain and Nerve) 27: 1249–1260

    CAS  Google Scholar 

  • Nagatsu T, Kato T, Numata (Sudo) Y, Ikuta K, Sano M, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Hori A, Narabayashi H (1977) Phenylethanolamine N-methyltrans-ferase and other enzymes of catecholamine metabolism in human brain. Clin Chim Acta 75: 221–232

    CAS  Google Scholar 

  • Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J Biol Chem 239: 2910–2917

    Google Scholar 

  • Nagatsu T, Mizutani K, Sudo Y, Nagatsu I (1972) Tyrosine hydroxylase in human adrenal glands and human pheochromocytoma. Clin Chim Acta 39: 417–424

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T, Yamaguchi T, Kato T, Sugimoto T, Matsuura S, Akino M, Nagatsu I, Iizuka R, Narabayashi H (1981) Biopterin in human brain and urine from controls and parkinsonian patients: application of a new radioimmunoassay. Clin Chim Acta 109: 305–311

    Article  PubMed  CAS  Google Scholar 

  • O’Malley KL, Anhalt MJ, Martin BM, Kalsoe JR, Winfield SL, Ginns EI (1987) Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5’-alternative splice sites responsible for multiple mRNAs. Biochemistry 26: 6910–6914

    Article  PubMed  Google Scholar 

  • Ozaki N, Nakahara D, Mogi M, Harada M, Kiuchi K, Kaneda N, Miura Y, Kasahara Y, Nagatsu T (1988) Inactivation of tyrosine hydroxylase in rat striatum by 1 -methyl-4-phenylpyridinium ion (MPP+). Neurosci Lett 85: 228–232

    Article  PubMed  CAS  Google Scholar 

  • Pileblad E, Fornstedt B, Clark D, Carlsson A (1985) Acute effects of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine metabolism in mouse and rat striatum. J Pharm Pharmacol 37: 707–712

    PubMed  CAS  Google Scholar 

  • Rush RA, Kindler SH, Udenfriend S (1974) Homospecific activity, an immunological index of enzyme homogeneity; changes during the purification of dopamine ß-hydroxylase. Biochem Biophys Res Commun 61: 38–44

    Article  PubMed  CAS  Google Scholar 

  • Togari A, Kano H, Oka K, Nagatsu T (1983) Simultaneous simple purification of tyrosine hydroxylase and dihydropteridine reductase. Anal Biochem 132: 183–189

    Article  PubMed  CAS  Google Scholar 

  • Zigmond RE, Schwarzchild MA, Rittenhouse AR (1989) Acute regulation of tyrosine hydroxylase by nerve activity and by neurotransmitters via phosphorylation. Ann Rev Neurosci 12: 415–461

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan

    Prof. Dr. T. Nagatsu

Authors
  1. Prof. Dr. T. Nagatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neurochemistry, Fujita Health University, Aichi, Japan

    Toshiharu Nagatsu

  2. Neurological Clinic, Tokyo, Japan

    Hirotaro Narabayashi

  3. Department of Neurology, Jichi Medical School, Tochigi-ken, Japan

    Mitsuo Yoshida

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer-Verlag/Wien

About this paper

Cite this paper

Nagatsu, T. (1991). Tyrosine hydroxylase in relation to Parkinson’s disease: a historical overview and future prospect. In: Nagatsu, T., Narabayashi, H., Yoshida, M. (eds) Parkinson’s Disease. From Clinical Aspects to Molecular Basis. Key Topics in Brain Research. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9146-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-9146-0_1

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-82272-2

  • Online ISBN: 978-3-7091-9146-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation