チロシンヒドロキシラーゼ

チロシンヒドロキシラーゼ（Tyrosine hydroxylase、EC 1.14.16.2）、チロシン 3-モノオキシゲナーゼ（tyrosine 3-monooxygenase）は、チロシンをジヒドロキシフェニルアラニン（DOPA）に変換する酵素である。DOPAはノルアドレナリンとアドレナリンの前駆体であるドーパミンの前駆体である。 この酸素添加酵素はカテコールアミンを含むすべての細胞の細胞質基質で見られる。この最初の反応はカテコールアミン合成において律速段階である。 この酵素は特殊で、インドール誘導体は受け入れない。カテコールアミンの合成に関わる他の多くの酵素も同様である。 チロシンヒドロキシラーゼはα-メチルチロシン（メチロシン）によって抑制することができるが、それはノルアドレナリン合成の調節の効果的手段にはならない。この薬品は稀にしか使われないが、褐色細胞腫と高血圧の治療には有用である。 Pharmacology 5th Ed, by Rang, Dale Ritter and Moore Hedstrand H, Ekwall O, Haavik J, et al (January 2000). “Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I”. Biochem. Biophys. Res. Commun. 267 (1): 456–61. doi:10.1006/bbrc.1999.1945. PMID 10623641. http://linkinghub.elsevier.com/retrieve/pii/S0006-291X(99)91945-9.  Masserano JM, Weiner N (1983). “Tyrosine hydroxylase regulation in the central nervous system.”. Mol. Cell. Biochem. 53-54 (1-2): 129–52. PMID 6137760.  Meloni R, Biguet NF, Mallet J (2002). “Post-genomic era and gene discovery for psychiatric diseases: there is a new art of the trade? The example of the HUMTH01 microsatellite in the Tyrosine Hydroxylase gene.”. Mol. Neurobiol. 26 (2-3): 389–403. PMID 12428766.  Joh TH, Park DH, Reis DJ (1979). “Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation.”. Proc. Natl. Acad. Sci. U.S.A. 75 (10): 4744–8. PMID 33381.  Haycock JW, Ahn NG, Cobb MH, Krebs EG (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. U.S.A. 89 (6): 2365–9. PMID 1347949.  Haycock JW (1990). “Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40.”. J. Biol. Chem. 265 (20): 11682–91. PMID 1973163.  Craig SP, Buckle VJ, Lamouroux A, et al. (1986). “Localization of the human tyrosine hydroxylase gene to 11p15: gene duplication and evolution of metabolic pathways.”. Cytogenet. Cell Genet. 42 (1-2): 29–32. PMID 2872999.  Grima B, Lamouroux A, Boni C, et al. (1987). “A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics.”. Nature 326 (6114): 707–11. doi:10.1038/326707a0. PMID 2882428.  Kaneda N, Kobayashi K, Ichinose H, et al. (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 (3): 971–5. PMID 2887169.  Kobayashi K, Kaneda N, Ichinose H, et al. (1987). “Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3.”. Nucleic Acids Res. 15 (16): 6733. PMID 2888085.  O'Malley KL, Anhalt MJ, Martin BM, et al. (1988). “Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs.”. Biochemistry 26 (22): 6910–4. PMID 2892528.  Le Bourdellès B, Boularand S, Boni C, et al. (1988). “Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms.”. J. Neurochem. 50 (3): 988–91. PMID 2892893.  Ginns EI, Rehavi M, Martin BM, et al. (1988). “Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector.”. J. Biol. Chem. 263 (15): 7406–10. PMID 2896667.  Kobayashi K, Kaneda N, Ichinose H, et al. (1988). “Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types.”. J. Biochem. 103 (6): 907–12. PMID 2902075.  Coker GT, Vinnedge L, O'Malley KL (1989). “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 (3): 1341–7. PMID 2905129.  Vulliet PR, Woodgett JR, Cohen P (1984). “Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase.”. J. Biol. Chem. 259 (22): 13680–3. PMID 6150037.  Zhou QY, Quaife CJ, Palmiter RD (1995). “Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development.”. Nature 374 (6523): 640–3. doi:10.1038/374640a0. PMID 7715703.  Lüdecke B, Bartholomé K (1995). “Frequent sequence variant in the human tyrosine hydroxylase gene.”. Hum. Genet. 95 (6): 716. PMID 7789962.  Lüdecke B, Dworniczak B, Bartholomé K (1995). “A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome.”. Hum. Genet. 95 (1): 123–5. PMID 7814018.  Knappskog PM, Flatmark T, Mallet J, et al. (1996). “Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.”. Hum. Mol. Genet. 4 (7): 1209–12. PMID 8528210.  フェニルアラニンヒドロキシラーゼ トリプトファンヒドロキシラーゼ Tyrosine hydroxylase - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）