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). 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.

Older examples of inhibitors mentioned in the literature include oudenonecite journal |author=Ono M, Okamoto M, Kawabe N, Umezawa H, Takeuchi T |title=Oudenone, a novel tyrosine hydroxylase inhibitor from microbial origin |journal=J. Am. Chem. Soc. |volume=93 |issue=5 |pages=1285–6 |year=1971 |month=March |pmid=5545929 |doi= |url=] and aquayamycin.cite journal |author=Ayukawa S, Takeuchi T, Sezaki M, Hara T, Umezawa H |title=Inhibition of tyrosine hydroxylase by aquayamycin |journal=J. Antibiot. |volume=21 |issue=5 |pages=350–3 |year=1968 |month=May |pmid=5726288 |doi= |url=]

References

* Pharmacology 5th Ed, by Rang, Dale Ritter and Moore
*

Further reading

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citations =
*cite journal | author=Masserano JM, Weiner N |title=Tyrosine hydroxylase regulation in the central nervous system. |journal=Mol. Cell. Biochem. |volume=53-54 |issue= 1-2 |pages= 129–52 |year= 1983 |pmid= 6137760 |doi=
*cite journal | author=Meloni R, Biguet NF, Mallet J |title=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. |journal=Mol. Neurobiol. |volume=26 |issue= 2-3 |pages= 389–403 |year= 2002 |pmid= 12428766 |doi=
*cite journal | author=Joh TH, Park DH, Reis DJ |title=Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=75 |issue= 10 |pages= 4744–8 |year= 1979 |pmid= 33381 |doi=
*cite journal | author=Haycock JW, Ahn NG, Cobb MH, Krebs EG |title=ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 6 |pages= 2365–9 |year= 1992 |pmid= 1347949 |doi=
*cite journal | author=Haycock JW |title=Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40. |journal=J. Biol. Chem. |volume=265 |issue= 20 |pages= 11682–91 |year= 1990 |pmid= 1973163 |doi=
*cite journal | author=Craig SP, Buckle VJ, Lamouroux A, "et al." |title=Localization of the human tyrosine hydroxylase gene to 11p15: gene duplication and evolution of metabolic pathways. |journal=Cytogenet. Cell Genet. |volume=42 |issue= 1-2 |pages= 29–32 |year= 1986 |pmid= 2872999 |doi=
*cite journal | author=Grima B, Lamouroux A, Boni C, "et al." |title=A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. |journal=Nature |volume=326 |issue= 6114 |pages= 707–11 |year= 1987 |pmid= 2882428 |doi= 10.1038/326707a0
*cite journal | author=Kaneda N, Kobayashi K, Ichinose H, "et al." |title=Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. |journal=Biochem. Biophys. Res. Commun. |volume=146 |issue= 3 |pages= 971–5 |year= 1987 |pmid= 2887169 |doi=
*cite journal | author=Kobayashi K, Kaneda N, Ichinose H, "et al." |title=Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3. |journal=Nucleic Acids Res. |volume=15 |issue= 16 |pages= 6733 |year= 1987 |pmid= 2888085 |doi=
*cite journal | author=O'Malley KL, Anhalt MJ, Martin BM, "et al." |title=Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs. |journal=Biochemistry |volume=26 |issue= 22 |pages= 6910–4 |year= 1988 |pmid= 2892528 |doi=
*cite journal | author=Le Bourdellès B, Boularand S, Boni C, "et al." |title=Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. |journal=J. Neurochem. |volume=50 |issue= 3 |pages= 988–91 |year= 1988 |pmid= 2892893 |doi=
*cite journal | author=Ginns EI, Rehavi M, Martin BM, "et al." |title=Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector. |journal=J. Biol. Chem. |volume=263 |issue= 15 |pages= 7406–10 |year= 1988 |pmid= 2896667 |doi=
*cite journal | author=Kobayashi K, Kaneda N, Ichinose H, "et al." |title=Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. |journal=J. Biochem. |volume=103 |issue= 6 |pages= 907–12 |year= 1988 |pmid= 2902075 |doi=
*cite journal | author=Coker GT, Vinnedge L, O'Malley KL |title=Characterization of rat and human tyrosine hydroxylase genes: functional expression of both promoters in neuronal and non-neuronal cell types. |journal=Biochem. Biophys. Res. Commun. |volume=157 |issue= 3 |pages= 1341–7 |year= 1989 |pmid= 2905129 |doi=
*cite journal | author=Vulliet PR, Woodgett JR, Cohen P |title=Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase. |journal=J. Biol. Chem. |volume=259 |issue= 22 |pages= 13680–3 |year= 1984 |pmid= 6150037 |doi=
*cite journal | author=Zhou QY, Quaife CJ, Palmiter RD |title=Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development. |journal=Nature |volume=374 |issue= 6523 |pages= 640–3 |year= 1995 |pmid= 7715703 |doi= 10.1038/374640a0
*cite journal | author=Lüdecke B, Bartholomé K |title=Frequent sequence variant in the human tyrosine hydroxylase gene. |journal=Hum. Genet. |volume=95 |issue= 6 |pages= 716 |year= 1995 |pmid= 7789962 |doi=
*cite journal | author=Lüdecke B, Dworniczak B, Bartholomé K |title=A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome. |journal=Hum. Genet. |volume=95 |issue= 1 |pages= 123–5 |year= 1995 |pmid= 7814018 |doi=
*cite journal | author=Knappskog PM, Flatmark T, Mallet J, "et al." |title=Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. |journal=Hum. Mol. Genet. |volume=4 |issue= 7 |pages= 1209–12 |year= 1996 |pmid= 8528210 |doi=

External links

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