Skip to main content
SpringerLink
Log in
Book cover

Pharmacology of Endogenous Neurotoxins pp 209–220Cite as

Birkhäuser

Tyrosine Hydroxylase: Biochemical Properties and Short-term Regulation in vitro and in vivo

  • Chapter

  • 105 Accesses

Abstract

Tyrosine hydroxylase (TH, EC 1.14.16.2, tyrosine 3-monooxygenase) catalyzes the first step in the biosynthesis of catecholamines (dopamine, noradrenaline and adrenaline) (Fig. 1), hydroxylating tyrosine to L-3,4-dihydroxyphenylalanine (L-dopa) (Nagatsu et al. 1964). Since it is a rate-limiting step, the regulation of its activity as well as amounts of enzyme protein play a central role in controlling the synthesis of catecholamines. These are known to be involved in many diseases, including neurological disorders (Parkinson’s disease, dystonia, manic depressive illness, schizophrenia), hypertension and diabetes mellitus. The physiological importance of TH has been evidenced by recent studies showing that targeted disruption of the TH gene results in mid-gestational lethality: about 90% of mutant embryos die between embryonic days 11.5 and 15.5, apparently of cardiovascular failure (Zhou et al., 1995; Kobayashi et al., 1995).

This is a preview of subscription content, 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albert K.A., Helmer-Matyjek E., Nairn A.C., Muller T.H., Haycock J.W., Greene L.A., Goldstein M., and Greengard P. (1984) Calcium/phospholipid-dependent protein kinase (protein kinase C) phosphorylates and activates tyrosine hydroxylase. Proc. Natl. Acad. Sci. USA 81:7713–7717.

    Article  PubMed  CAS  Google Scholar 

  • Almas B., Le Bourdelles B., Flatmark T., Mallet J., and Haavik J. (1992) Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine binding and phosphorylation. Structure/activity studies and mechanistic implications. Eur. J. Biochem. 209:249–255.

    Article  PubMed  CAS  Google Scholar 

  • Anagnoste B., Shirron C., Friedman E., and Goldstein M. (1974) Effect of dibutyryl cyclic adenosine monophosphate on 14C-dopamine biosynthesis in rat brain striatal slices. J. Pharmacol. Exp. Ther. 191:370–376.

    PubMed  CAS  Google Scholar 

  • Andersson K.K., Cox D.D., Que L. Jr., Flatmark T., and Haavik J. (1988) Resonance Raman studies on the blue-green-colored bovine adrenal tyrosine 3-monooxygenase (tyrosine hydroxylase). Evidence that the feedback inhibitors adrenaline and noradrenaline are coordinated to iron. J. Biol. Chem. 263:18621–18626.

    PubMed  CAS  Google Scholar 

  • Bean A.J., Shepard P.D., Bunney B.S., Nestler E.J., and Roth R.H. (1988) The effects of pertussis toxin on autoreceptor-mediated inhibition of dopamine synthesis in the rat striatum. Mol. Pharmacol. 34:715–718.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Funakoshi H., Okuno S., and Fujisawa H. (1991) Different effects on activity caused by phosphorylation of tyrosine hydroxylase at serine 40 by three multifunctional protein kinases. J. Biol. Chem. 266:15614–15620.

    PubMed  CAS  Google Scholar 

  • Furukawa Y., Ikuta N., Omata S., Yamauchi T., Isobe T., and Ichimura T. (1993) Demonstration of the phosphorylation-dependent interaction of tryptophan hydroxylase with the 14–3–3 protein. Biochem. Biophys. Res. Commun. 194:144–149.

    Article  PubMed  CAS  Google Scholar 

  • Greene L.A., and Kaplan D.R. (1995) Early events in neurotrophin signalling via Trk and p75 receptors. Curr. Opin. Neurobiol. 5:579–587.

    Article  PubMed  CAS  Google Scholar 

  • Grima B., Lamouroux A., Blanot F., Faucon Biguet N., and Mallet J. (1985) Complete coding sequence of rat tyrosine hydroxylase mRNA. Proc. Natl. Acad. Sci. USA 82:617–621.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Haavik J., Andersson K.K., Petersson L., and Flatmark T. (1988) Soluble tyrosine hydroxylase (tyrosine 3-monooxygenase) from bovine adrenal medulla: large-scale purification and physicochemical properties. Biochim. Biophys. Acta 953:142–156.

    Article  PubMed  CAS  Google Scholar 

  • Haavik J., Schelling D.L., Campbell D.G., Andersson K.K., Flatmark T., and Cohen P. (1989) Identification of protein phosphatase 2A as the major tyrosine hydroxylase phosphatase in adrenal medulla and corpus striatum: evidence from the effects of okadaic acid. FEBS Lett. 251:36–42.

    Article  PubMed  CAS  Google Scholar 

  • Haavik J., Le Bourdelles B., Martinez A., Flatmark T., and Mallet J. (1991) Recombinant human tyrosine hydroxylase isozymes. Reconstitution with iron and inhibitory effect of other metal ions. Eur. J. Biochem. 199:371–378.

    Article  PubMed  CAS  Google Scholar 

  • Hall EL., Braun R.K., Mihara K., Fung Y.K., Berndt N., Carbonara-Hall D.A., and Vulliet P.R. (1992) Characterization, of the cytoplasmic proline-directed protein kinase in proliferative cells and tissues as a heterodimer comprised of p34cdc2 and p58cyclin A. J. Biol. Chem. 266:17430–17440.

    Google Scholar 

  • Haycock J.W., and Haycock D.A. (1991) Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes. J. Biol. Chem. 266:5650–5657.

    PubMed  CAS  Google Scholar 

  • Haycock J.W., Ahn N.G., Cobb M.H., and Krebs E.G. (1992) ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ. Proc. Natl. Acad. Sci. USA 89:2365–2369.

    Article  PubMed  CAS  Google Scholar 

  • Hirata Y., and Nagatsu T. (1985) Evidence for the involvement of Ca2+-calmodulin and cyclic AMP in the regulation of the tyrosine hydroxylase system in rat striatal tissue slices. Biochem. Pharmacol. 34:2637–2643.

    Article  PubMed  CAS  Google Scholar 

  • Hufton S.E., Jennings I.G., and Cotton R.G.H. (1995) Structure and function of the aromatic amino acid hydroxylases. Biochem. J. 311:353–366.

    PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Ishii A., Kiuchi K., Kobayashi R., Sumi M., Hidaka H., and Nagatsu T. (1991) A selective Ca2+/calmodulin-dependent protein kinase II inhibitor, KN-62, inhibits the enhanced phosphorylation and the activation of tyrosine hydroxylase by 56 mM K+ in rat pheochromocytoma PC12h cells. Biochem. Biophys. Res. Commun. 176:1051–1056.

    Article  PubMed  CAS  Google Scholar 

  • Kaneda N., Kobayashi K., Ichinose H., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., and Nagatsu T. (1987) Isolation of a 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 

  • Kobayashi K., Morita S., Sawada H., Mizuguchi T., Yamada K., Nagatsu I., Hata T., Watanabe Y., Fujita K., and Nagatsu T. (1995) Targeted disruption of the tyrosine hydroxylase locus results in severe catecholamine depletion and perinatal lethality in mice. J. Biol. Chem. 270:27235–27243.

    Article  PubMed  CAS  Google Scholar 

  • Kumer S.C., and Vrana K.E. (1996) Intricate regulation of tyrosine hydroxylase activity and gene expression. J. Neurochem. 67:443–462.

    Article  PubMed  CAS  Google Scholar 

  • Le Bourdelles B., Horellou P., Le Caer J.-P., Denefle P., Latta M., Haavik J., Guibert B., Mayaux J.-F., and Mallet J. (1991) Phosphorylation of human recombinant tyrosine hydroxylase isoforms 1 and 2: An additional phosphorylated residue in isoform 2, generated through alternative splicing. J. Biol. Chem. 266:17124–17130.

    PubMed  Google Scholar 

  • Lee K.Y., Seeley P.J., Muller T.H., Helmer-Matyjek E., Sabban E., Goldstein M., and Greene L.A. (1985) Regulation of tyrosine hydroxylase phosphorylation in PC12 pheochromocytoma cells by elevated K+ and nerve growth factor. Evidence for different mechanisms of action. Mol. Pharmacol. 28:220–228.

    PubMed  CAS  Google Scholar 

  • Lohse D.L., and Fitzpatrick P.F. (1993) Identification of the intersubunit binding region in rat tyrosine hydroxylase. Biochem. Biophys. Res. Commun. 197:1543–1548.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Nagatsu T., Oka K., and Kato T. (1979) Highly sensitive assay for tyrosine hydroxylase activity by high-performance liquid chromatography. J. Chromatogr. 163:247–252.

    PubMed  CAS  Google Scholar 

  • Nagatsu T. (1983) Analysis of monooxygenases in catecholamine biosynthesis: tyrosine hydroxylase and dopamine-β-hydroxylase. In: Methods in Biogenic Amine Research (Parvez S., Nagatsu T., Nagatsu I., and Parvez H., eds.), pp. 329–357. Elsevier Science Publishers B.V.

    Google Scholar 

  • Nagatsu T. (1995) Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. In: Essays in Biochemistry, Vol. 30 (Apps D.K. and Tipton K.F., eds.), pp. 15–35. Portland Press, London.

    Google Scholar 

  • Naoi M., Maruyama W., Dostert P., Hashizume Y., Nakahara D., Takahashi T., and Ota M. (1996) Dopamine-derived endogenous 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: biochemical, pathological and behavioral studies. Brain Res. 709:285–295.

    Article  PubMed  CAS  Google Scholar 

  • Okuno S., and Fujisawa H. (1985) A new mechanism for regulation of tyrosine 3-monooxygenase by end product and cyclic AMP-dependent protein kinase. J. Biol. Chem. 260: 2633–2635.

    PubMed  CAS  Google Scholar 

  • Okuno S., and Fujisawa H. (1991) Conversion of tyrosine hydroxylase to stable and inactive form by the end products. J. Neurochem. 57:53–60.

    Article  PubMed  CAS  Google Scholar 

  • Ramsey A.J., Daubner S.C., Ehrlich J.I., and Fitzpatrick P.F. (1995) Identification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidinyl residues. Protein Sei. 4:2082–2086.

    Article  CAS  Google Scholar 

  • Ribeiro P., Wang Y., Citron B.A., and Kaufman S. (1992) Regulation of recombinant rat tyrosine hydroxylase by dopamine. Proc. Natl. Acad. Sei. USA 89:9593–9597.

    Article  CAS  Google Scholar 

  • Roskoski R. Jr., and Roskoski L.M. (1987) Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second messenger systems. J. Neurochem. 48:236–242.

    Article  PubMed  CAS  Google Scholar 

  • Roskoski R. Jr., Vulliet P.R., and Glass D.B. (1987) Phosphorylation of tyrosine hydroxylase by cyclic GMP-dependent protein kinase. J. Neurochem. 48:840–845.

    Article  PubMed  CAS  Google Scholar 

  • Roth R.H., and Elsworth J.D. (1995) Biochemical pharmacology of midbrain dopamine neurons. In: Psychopharmacology: The Fourth Generation of Progress (Bloom F.E. and Kupfer D.J., eds.), pp. 227–243. Raven Press, New York.

    Google Scholar 

  • Stokes A.H., Brown B.G., Lee C.K., Doolittle D.J., and Vrana K.E. (1996) Dopamine covalently modifies DNA in a tyrosinase-enhanced manner. In: Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances (Fiskum G., ed.), pp. 299–304. Plenum Press, New York.

    Google Scholar 

  • Sutherland C., Alterio J., Campbell D.G., Le Bourdelles B., Mallet J., Haavik J., and Cohen P. (1993) Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2. Eur. J. Biochem. 217:715–722.

    Article  PubMed  CAS  Google Scholar 

  • Vrana K.E., Walker S.J., Rucker P., and Liu X. (1994) A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation. J. Neurochem. 63:2014–2020.

    Article  PubMed  CAS  Google Scholar 

  • Vulliet P.R., Langan T.A., and Weiner N. (1980) Tyrosine hydroxylase: A substrate of cyclic AMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 77:92–96.

    Article  PubMed  CAS  Google Scholar 

  • Vulliet P.R., Hall F.L., Mitchell J.P., and Hardie D.G. (1989) Identification of a novel proline-directed serine/threonine protein kinase in rat pheochromocytoma. J. Biol. Chem. 264:16292–16298.

    PubMed  CAS  Google Scholar 

  • Walker S.J., Liu X., Roskoski R., and Vrana K.E. (1994) Catalytic core of rat tyrosine hydroxylase: terminal deletion analysis of bacterially expressed enzyme. Biochim. Biophys. Acta 1206:113–119.

    Article  PubMed  CAS  Google Scholar 

  • Westerink B.H.C., De Vries J.B., and Duran R. (1990) Use of microdialysis for monitoring tyrosine hydroxylase activity in the brain of conscious rats. J. Neurochem. 54:381–387.

    Article  PubMed  CAS  Google Scholar 

  • Wu J., Filer D., Friedhoff A.J., and Goldstein M. (1992) Site-directed mutagenesis of tyrosine hydroxylase. J. Biol. Chem. 267:25754–25758.

    PubMed  CAS  Google Scholar 

  • Yamauchi T., and Fujisawa H. (1981) Tyrosine-3-monooxygenase is phosphorylated by Ca2+-calmodulin dependent protein kinase followed by activation by activator protein. Biochem. Biophys. Res. Commun. 100:807–813.

    Article  CAS  Google Scholar 

  • Zhou Q-Y., Qualfe C.J., and Palmiter R.D. (1995) Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development. Nature 374:640–643.

    Article  PubMed  CAS  Google Scholar 

  • Zigmond R.E., Schwarzschild M.A., and Rittenhouse A.R. (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

Authors
  1. Yoko Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Neurology, Medical University of Lübeck, Lübeck, Germany

    Andreas Moser

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hirata, Y. (1998). Tyrosine Hydroxylase: Biochemical Properties and Short-term Regulation in vitro and in vivo. In: Moser, A. (eds) Pharmacology of Endogenous Neurotoxins. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4612-2000-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-2000-8_9

  • Publisher Name: Birkhäuser, Boston, MA

  • Print ISBN: 978-1-4612-7375-2

  • Online ISBN: 978-1-4612-2000-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation