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20-September-2008 09:55:50 - Tyrosine hydroxylase Redirected from Tyrosine hydroxylase inhibitor Jump to: navigation, search Tyrosine hydroxylase PDB Available structures: 1toh, 2toh Identifiers Symbols TH; TYH External IDs OMIM: 191290 MGI: 98735 HomoloGene: 307 EC number 1.14.16.2 Gene ontology Molecular function: monooxygenase activity tyrosine 3-monooxygenase activity iron ion binding metal ion binding Cellular component: nucleus cytoplasm Biological process: synaptic transmission, dopaminergic synaptic transmission heart development learning memory mating behavior locomotory behavior regulation of heart contraction aromatic amino acid family metabolic process organ morphogenesis neurotransmitter biosynthetic process catecholamine biosynthetic process eating behavior RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 7054 21823 Ensembl ENSG00000180176 ENSMUSG00000000214 Uniprot P07101 Q3UTB3 Refseq NM_000360 mRNA NP_000351 protein NM_009377 mRNA NP_033403 protein Location Chr 11: 2.14 - 2.15 Mb Chr 7: 142.7 - 142.71 Mb Pubmed search 1 2 Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine DOPA. DOPA is a precursor for dopamine which in turn is a precursor for norepinephrine noradrenaline and epinephrine adrenaline. The enzyme, an oxygenase, is found in the cytosol of all cells containing catecholamines. This initial reaction is the rate limiting step in the production of catecholamines. The enzyme is highly specific, not accepting indole derivatives - which is unusual as many other enzymes involved in the production of catecholamines do. Tyrosine hydroxylase catalyzes tyrosine to dihydroxyphenylalanine Tyrosine hydroxylase catalyzes tyrosine to dihydroxyphenylalanine Contents 1 Clinical significance 2 References 3 Further reading 4 External links Clinical significance Tyrosine hydroxylase can be inhibited by the drug α-methyl tyrosine Metirosine, however it is not an effective means of regulating noradrenaline synthesis. This drug is rarely used, but it is useful in treating pheochromocytoma and also resistant hypertension. Dopamine Dopamine Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome APS type I. Older examples of inhibitors mentioned in the literature include oudenone1 and aquayamycin.2 References ^ Ono M, Okamoto M, Kawabe N, Umezawa H, Takeuchi T March 1971. Oudenone, a novel tyrosine hydroxylase inhibitor from microbial origin. J. Am. Chem. Soc. 93 5: 1285-6. PMID 5545929. ^ Ayukawa S, Takeuchi T, Sezaki M, Hara T, Umezawa H May 1968. Inhibition of tyrosine hydroxylase by aquayamycin. J. Antibiot. 21 5: 350-3. PMID 5726288. 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. Further reading 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. External links MeSH Tyrosine+hydroxylase v d e Carrier proteins, metalloproteins: iron-binding proteins heme Ferritin Bacterioferritin - Lactoferrin - Transferrin nonheme Hemerythrin - Inositol oxygenase - Iron-sulfur protein - Lipoxygenase - Tyrosine hydroxylase v d e Oxidoreductases: dioxygenases, including steroid hydroxylases EC 1.14 1.14.11 - 2-oxoglutarate Prolyl hydroxylase - Lysyl hydroxylase 1.14.13 - NADH or NADPH Flavin-containing monooxygenase - Nitric oxide synthase NOS1, NOS2A, NOS3 - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 -51A1 1.14.14 - reduced flavin or flavoprotein 19A1 - 2D6 - 2E1 1.14.15 - reduced iron-sulfur protein 11B1 - 11B2 - 11A1 1.14.16 - reduced pteridine Phenylalanine hydroxylase - Tyrosine hydroxylase - Tryptophan hydroxylase 1.14.17 - reduced ascorbate Dopamine beta hydroxylase 1.14.18-19 - other Tyrosinase - Stearoyl-CoA desaturase-1 1.14.99 - miscellaneous Cyclooxygenase - Heme oxygenase HMOX1 - Squalene monooxygenase - 17A1 - 21A2 v d e Metabolism: amino acid metabolism - neurotransmitter enzymes histidine→histamine anabolism: Histidine decarboxylase catabolism: Histamine N-methyltransferase - Amine oxidase tyrosine→dopamine→epinephrine anabolism: Tyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase catabolism: Catechol-O-methyl transferase - Monoamine oxidase glutamate→GABA anabolism: Glutamate decarboxylase catabolism: 4-aminobutyrate aminotransferase - 4-aminobutyrate transaminase tryptophan→serotonin→melatonin Tryptophan hydroxylase - Aromatic L-amino acid decarboxylase - Acetylserotonin O-methyltransferase arginine→NO Nitric oxide synthase NOS1, NOS2A, NOS3 choline→Acetylcholine anabolism: Choline acetyltransferase catabolism: Cholinesterase Acetylcholinesterase, Butyrylcholinesterase see also intermediates Retrieved from http://en..org/wiki/Tyrosine_hydroxylase Categories: Genes on chromosome 11 | Human proteins | Enzymes | EC 1.14.16 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Español Français This page was last modified on 18 July 2008, at 06:12
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