Tyrosine hydroxylase
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] It does so using tetrahydrobiopterin as a coenzyme. 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]
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.
Clinical significance
Tyrosine hydroxylase can be inhibited by the drug α-methyl-para-tyrosine (Metirosine). This inhibition can lead to a depletion of dopamine and norepinepherine in the brain due to the lack of the precursor L-Dopa (L-3,4-dyhydroxyphenylalanine) which is synthesized by tyrosine hydroxylase. This drug is rarely used and can cause depression, but it is useful in treating pheochromocytoma and also resistant hypertension.
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]
Regulation
TH is increased acutely (minutes) by phosphorylation and chronically (days) by protein synthesis.[6] The phosphorylation can be sustained by nicotine for up to 48 hours.[7]
TH is decreased by the release of Catecholamines.
References
- ^ Kaufman S (1995). "Tyrosine hydroxylase". Adv. Enzymol. Relat. Areas Mol. Biol.. Advances in Enzymology - and Related Areas of Molecular Biology 70: 103–220. doi:10.1002/9780470123164.ch3. ISBN 9780470123164. 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.
- ^ http://www.mendeley.com/research/sustained-phosphorylation-tyrosine-hydroxylase-serine-40-novel-mechanism-maintenance-catecholamine-synthesis/
- ^ http://www.mendeley.com/research/sustained-phosphorylation-tyrosine-hydroxylase-serine-40-novel-mechanism-maintenance-catecholamine-synthesis/
Further reading
- 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. PMC 336196. PMID 33381. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=336196.
- 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. PMC 48658. PMID 1347949. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48658.
- 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. PMC 306135. PMID 2888085. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=306135.
- 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.
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PDB gallery
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1toh: TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT
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2toh: TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT
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External links
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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