Tyrosine hydroxylase: Definition from Answers.com

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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

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).^[1]^[2] DOPA is a precursor for dopamine which in turn is a precursor for norepinephrine (noradrenaline) and epinephrine (adrenaline). In humans, tyrosine hydroxylase is encoded by the TH gene.^[2]

1 Reaction
2 Clinical significance
3 References
4 Further reading
5 External links

Reaction

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

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

Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I.^[3]

Older examples of inhibitors mentioned in the literature include oudenone^[4] and aquayamycin.^[5]

References

^ Kaufman S (1995). "Tyrosine hydroxylase". Adv. Enzymol. Relat. Areas Mol. Biol. 70: 103–220. doi:10.1002/9780470123164.ch3. PMID 8638482.
^ ^a ^b Nagatsu T (1995). "Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology". Essays Biochem. 30: 15–35. PMID 8822146.
^ Hedstrand H, Ekwall O, Haavik J, Landgren E, Betterle C, Perheentupa J, Gustafsson J, Husebye E, Rorsman F, Kämpe O (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.
^ 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. doi:10.1021/ja00734a054. 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.

Masserano JM, Weiner N (1983). "Tyrosine hydroxylase regulation in the central nervous system.". Mol. Cell. Biochem. 53-54 (1-2): 129–52. doi:10.1007/BF00225250. 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. doi:10.1385/MN:26:2-3:389. 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. doi:10.1073/pnas.75.10.4744. 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. doi:10.1073/pnas.89.6.2365. 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. doi:10.1159/000132246. 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. doi:10.1016/0006-291X(87)90742-X. 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. doi:10.1093/nar/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. doi:10.1021/bi00396a007. 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. doi:10.1111/j.1471-4159.1988.tb03009.x. 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. doi:10.1016/S0006-291X(88)81022-2. 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. doi:10.1007/BF00209496. 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. doi:10.1007/BF00225091. 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. doi:10.1093/hmg/4.7.1209. PMID 8528210.

PDB Gallery

1toh: TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT

2toh: TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT

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 (FMO1, FMO2, FMO3, FMO4, FMO5) - Nitric oxide synthase (NOS1, NOS2A, NOS3) - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 - Lanosterol 14 alpha-demethylase

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 (BH4 dependent)	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

Metabolism: amino acid metabolism - neurotransmitter enzymes

monoamine

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

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	α-methyl-para-tyrosine (organic chemistry)
	kinase
	noradrenaline

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Tyrosine hydroxylase

Contents

Reaction

Clinical significance

References

Further reading

External links