My watch list
my.chemeurope.com  

my.chemeurope.com

With an accout for my.chemeurope.com you can always see everything at a glance – and you can configure your own website and individual newsletter.

  • My watch list
  • My saved searches
  • My saved topics
  • My newsletter
Register free of charge
Login  
eng  
DeutschEnglishFrançaisEspañol

Tyrosine hydroxylase



Tyrosine hydroxylase
PDB
Available structures: 1toh, 2toh
Identifiers
Symbol(s) TH; TYH
External IDs OMIM: 191290 MGI: 98735 Homologene: 307
EC number 1.14.16.2
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.

 

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.

 

Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I.

References

  • Pharmacology 5th Ed, by Rang, Dale Ritter and Moore
  • Biochemical and Biophysical Communications 267, 456-461 (2000) Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I

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.
v • d • e
Carrier proteins, metalloproteins: iron-binding proteins
hemeFerritin (Bacterioferritin) - Lactoferrin - Transferrin
nonhemeHemerythrin - Inositol oxygenase - Iron-sulfur protein - Lipoxygenase - Tyrosine hydroxylase
v • d • e
Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11 - 2-oxoglutarateProlyl hydroxylase - Lysyl hydroxylase
1.14.13 - NADH or NADPHFlavin-containing monooxygenase - Nitric oxide synthase - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 -51A1
1.14.14 - reduced flavin or flavoprotein19A1 - 2D6 - 2E1
1.14.15 - reduced iron-sulfur protein11B1 - 11B2 - 11A1
1.14.16 - reduced pteridinePhenylalanine hydroxylase - Tyrosine hydroxylase - Tryptophan hydroxylase
1.14.17 - reduced ascorbateDopamine beta hydroxylase
1.14.18-19 - otherTyrosinase - Stearoyl-CoA desaturase-1
1.14.99 - miscellaneousCyclooxygenase - Heme oxygenase (HMOX1) - Squalene monooxygenase - 17A1 - 21A2
v • d • e
Amino acid metabolism enzymes
phenylalanine→tyrosine→fumarate→TCAPhenylalanine hydroxylase - Tyrosine aminotransferase - 4-Hydroxyphenylpyruvate dioxygenase - Homogentisate 1,2-dioxygenase - Fumarylacetoacetate hydrolase
tyrosine→dopamine→epinephrineTyrosine hydroxylase - Aromatic L-amino acid decarboxylase - Dopamine beta hydroxylase - Phenylethanolamine N-methyltransferase
leucine→HMG-CoA (keto)Branched-chain alpha-keto acid dehydrogenase complex - Isovaleryl coenzyme A dehydrogenase - Methylcrotonyl-CoA carboxylase
isoleucine/valine→propionyl-CoABranched-chain alpha-keto acid dehydrogenase complex
methionine→cysteine→propionyl-CoAMethionine adenosyltransferase - Adenosylhomocysteinase - (or MTR) - Cystathionine beta synthase - Cystathionine gamma-lyase
propionyl-CoA→succinyl-CoA→TCAPropionyl-CoA carboxylase - Methylmalonyl-CoA mutase
serine→glycineSerine hydroxymethyltransferase
histidineto histamine: Histidine decarboxylase - to glutamate: Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase
tryptophan→serotonin→melatoninTryptophan hydroxylase - Aromatic L-amino acid decarboxylase - 5-hydroxyindole-O-methyltransferase
asparagine→aspartate→oxaloacetate→TCAAsparaginase/Asparagine synthetase - Aspartate transaminase
glutamateGlutaminase - Glutamate decarboxylase
lysine→ketoSaccharopine dehydrogenase
otherTyrosinase
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Tyrosine_hydroxylase". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE