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

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Summary

We cloned full-length cDNAs and genomic DNAs of human catocholamine-synthesizing enzymes, i.e., tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine β-hydroxylase (DBH), and phenythanolamine N-methyltransferase (PNMT), and determined the nucleotide sequences and the deduced amino acid sequences. Multiple mRNAs of human TH, human DBH, and human PNMT were discovered by cDNA cloning. Four types of human TH mRNAs are produced by althernative splicing mechanisms from a single gene. The multiple forms of human TH may give additional regulation to the human enzyme. We have succeeded in expressing human TH gene in transgnic mice. The 5′-flanking regions of the genes of human TH, DBH and PNMT contain possible transcription regulatory elements such as cyclic AMP responsive element (CRE) (TH, DBH, PNMT), glucocordicoid responsive element (GRE) (DBH, PNMT), and Sp1 (TH, PNMT) binding site.

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References

  • Axelrod J (1962) Purification and properties of phenylethanolamine N-methyltransferase. J Biol Chem 237: 1657–1660

    PubMed  CAS  Google Scholar 

  • Baetge EE, Behringer RR, Messsing A, Brinster RL, Palmiter RD (1988) Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina. Proc Natl Acad Sci USA 85: 3648–3652

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Coker GT III, Vinnedge L, O’Malley KL (1988) Characterization of rat and human tyrosine hydroxylase genes: functional expression of both promoters in neuronal and non-neuronal cell types. Biochem Biophys Res Commun 157: 1341–1347

    Article  PubMed  CAS  Google Scholar 

  • Dahlstrom A, Belmaker RH, Sandler M (eds) (1988) In: Progress in catecholamine research, part A. Basic aspects and peripheral mechanisms. Alan R Liss, New York, pp 1–613

    Google Scholar 

  • Friedman S, Kaufman S (1965) 3,4-Dihydroxyphenylethylamine β-hydroxylase. Physical properties, copper content, and role of copper in the catalytic activity. J Biol Chem 240: 4763–4773

    Google Scholar 

  • Fujisawa H, Okuno S (1987) Tyrosine 3-monooxygenase from rat adrenals. In: Kaufman S (ed) Methods in enzymology, vol 142. Academic Press, New York, pp 63–71

    Google Scholar 

  • Ginns EI, Rehari M, Martin BM, Weller M, O’Malley KL, La Marca ME, McAllister CG, Paul SM (1988) Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector. J Biol Chem 263: 7406–7410

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  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 

  • Horellou P, Le Bourdelles B, Clot-Humbert J, Guibert B, Leviel V, Mallet J (1988) Multiple human tyrosine hydroxylase enzymes, generated through alternative splicing, have different specific activities in Xenopus oocytes. J Neurochem 51: 652–655

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T (1989) Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun 164: 1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Ishii A, Hagihara M, Matsuura S, Uchida K, Kiuchi K, Kaneda N, Toya S, Kohsaka S, Nagatsu T (1990) Effect of (6R)- and (6S)-tetrahydrobiopterin on L-3,4-dihydroxy- phenylalanine (DOPA) formation in NRK fibroblasts transfected with human tyrosine hydroxylase type 2 cDNA. Neurochem Int 17: 625–632

    Article  PubMed  CAS  Google Scholar 

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

  • Kaneda N, Ichinose H, Kobayashi K, Oka K, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1988) Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis. J Biol Chem 263: 7672–7677

    PubMed  CAS  Google Scholar 

  • Kaneda N, Sasaoka T, Kobayashi K, Katsuki M, Yokoyama M, Nagatsu I, Kurosawa Y, Fujita K, Nagatsu T (1990) Production and analysis of transgenic mice carrying human tyrosine hydroxylase gene (in Japanese). Seikagaku (Jap Biochem Soc) 62: 975–975

    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 Press, Tokyo, and Karger, Basel, pp 53–56

    Google Scholar 

  • Kaneda N, Sasaoka T, Kobayashi K, Kiuchi K, Nagatsu I, Kurosawa Y, Fujita K, Yokoyama M, Nomura T, Katsuki M, Nagatsu T (1991) Tissue-specific and high-level expression of human tyrosine hydroxylase gene in transgenic mice. Neuron 6: 1–12

    Article  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: 6733–6733

    Article  PubMed  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 

  • Kobayashi K, Kurosawa Y, Fujita K, Nagatsu T (1989) Human dopamine β-hydroxylase gene: two mRNA types having different 3′-terminal regions are produced through alternative polyadenylation. Nucl Acids Res 17: 1089–1102

    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 

  • Lamouroux A, Vigny N, Facon Bigunet MC, Darmon R, Franck R, Henry J-P, Mallet J (1987) The primary structure of human dopamine β-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J 6: 3931–3937

    PubMed  CAS  Google Scholar 

  • Le Bourdellès B, Boularand S, Boni C, Horellou P, Dumas S, Grima B, Mallet J (1988) Analyses of the 5′-region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. J Neurochem 50: 988–991

    Article  PubMed  Google Scholar 

  • Lewis EJ, Harrington CA, Chikaraishi DM (1987) Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP. Proc Natl Acad Sci USA 84: 3550–3554

    Article  PubMed  CAS  Google Scholar 

  • Lovenberg W, Weissbach H, Udenfriend S (1962) Aromatic L-amino acid decarboxylase. J Biol Chem 237: 89–93

    PubMed  CAS  Google Scholar 

  • Man in’t Veld AJ, Boomsma F, Moleman P, Schalekamp MADH (1987) Congenital dopamine-beta-hydroxylase deficiency. A novel orthostatic syndrome. Lancet i: 183–187

    Google Scholar 

  • Matuura 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 activate 5,6,7,8-tetrahydropterin. J Biochem 98: 1341–1348

    Google Scholar 

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

    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 

  • 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 

  • Nagatsu T (1977) Dopamine-β-hydroxylase in blood and cerebrospinal fluid. Trends Biochem Sci 2: 217–219

    Article  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-methyltransferase 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, Oka K (1987) Tyrosine 3-monooxygenase from bovine adrenal medulla. In: Kaufman S (ed) Methods in enzymology, vol 142. Academic Press, New York, pp 56–62

    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 unine from controls and parkinsonian patients: application of a new radioimmunoassay. Clin Chim Acta 109: 305–311

    Article  PubMed  CAS  Google Scholar 

  • Nagatsu T, Yamaguchi T, Rahman MK, Trocewicz J, Oka K, Hirata Y, Nagatsu I, Narabayashi H, Kondo K, Iizuka R (1984) Catecholamine-related enzymes and the biopterin cofactor in Parkinson’s disease and related extrapyramidal diseases. In: Hassler RG, Christ JF (eds) Advances in neurology, vol 40. Raven Press, New York, pp 467–473

    Google Scholar 

  • O’Malley KL, Anhalt MJ, Martin BM, Kelsoe 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 

  • Robertson D, Goldberg MR, Onrot J, Hollister AS, Wiley R, Thompson JR, Robertson RM (1986) Isolated failure of autonomic noradrenergic neurotransmission. N Engl J Med 314: 1494–1497

    Article  PubMed  CAS  Google Scholar 

  • Sasaoka T, Kaneda N, Kurosawa Y, Fujita K, Nagatsu T (1989) Structures of human phenylethanolamine N-methyltransferase gene: existence of two types of mRNA with different transcription initiation sites. Neurochem Int 15: 555–565

    Article  PubMed  CAS  Google Scholar 

  • Sumi C, Ichinose H, Nagatsu T (1990) Characterization of recombinant human aromatic L-amino acid decarloxylase expressed in COS cells. J Neurochem 55: 1075–1078

    Article  PubMed  CAS  Google Scholar 

  • Tank AW, Weiner N (1987) Tyrosine 3-monooxygenase from rat pheochromocytoma. In: Kaufman S (ed) Methods in enzymology, vol 142. Academic Press, New York, pp 71–82

    Google Scholar 

  • Uchida K, Takamatsu K, Kaneda N, Toya S, Tsukada Y, Kurosawa Y, Fujita K, Nagatsu T, Kohsaka S (1988) Transfection of tyrosine hydroxylase cDNA into C6 cell. Proc Jpn Acad Ser B 64: 290–293

    Article  CAS  Google Scholar 

  • Uchida K, Takamatsu T, Kaneda N, Toya S, Tsukada Y, Kurosawa Y, Fujita K, Nagatsu T, Kohsaka S (1989) Synthesis of L-3,4-dihydroxyphenylanin by tyrosine hydroxylase cDNA-transfected C6 cells: application for intracerebral grafting. J Neurochem: 53: 728–732

    Article  PubMed  CAS  Google Scholar 

  • Uchida K, Ishii A, Kaneda N, Toya S, Nagatsu T, Kohsaka S (1990a) Tetrahydro- bioptenin-dependent production of L-DOPA in NRK fibroblasts fransfected with tyrosine hydroxylase cDNA: future use for intracerebral grafting. Neurosci Lett 109: 282–286

    Article  PubMed  CAS  Google Scholar 

  • Uchida K, Toya S, Tsukada S, Nagatsu T, Kohsaka S (1990b) Transfection of tyrosine hydroxylase cDNA into non-neuronal cells: application for intracerebral grafting. 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 79–93

    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: 415–416

    Article  PubMed  CAS  Google Scholar 

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© 1991 Springer-Verlag/Wien

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Nagatsu, T. et al. (1991). Genes of human catecholamine-synthesizing enzymes. 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_3

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  • DOI: https://doi.org/10.1007/978-3-7091-9146-0_3

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-82272-2

  • Online ISBN: 978-3-7091-9146-0

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