酪氨酸羟化酶
酪氨酸羟化酶（英語：Tyrosine hydroxylase）或酪氨酸3-单加氧酶（英語：tyrosine 3-monooxygenase）是负责催化氨基酸L-酪氨酸转变为二羟基苯丙氨酸（多巴）的酶[1][2]。因此它使用四氢生物蝶呤作为辅酶。多巴是多巴胺的一个前体，相应地，后者亦是去甲肾上腺素与肾上腺素的前体。在人体中，酪氨酸羟化酶由TH基因编码[2]。
| 酪氨酸羟化酶 | |||||||||||||
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| 标识 | |||||||||||||
| 代号 | TH; TYH | ||||||||||||
| 扩展标识 | 遗传学：191290 鼠基因：98735 同源基因：307 GeneCards: TH Gene | ||||||||||||
| EC編號 | 1.14.16.2 | ||||||||||||
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| RNA表达模式 | |||||||||||||
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| 更多表达数据 | |||||||||||||
| 直系同源体 | |||||||||||||
| 物种 | 人类 | 小鼠 | |||||||||||
| Entrez | 7054 | 21823 | |||||||||||
| Ensembl | ENSG00000180176 | ENSMUSG00000000214 | |||||||||||
| UniProt | P07101 | Q3UTB3 | |||||||||||
| mRNA序列 | NM_000360 | NM_009377 | |||||||||||
| 蛋白序列 | NP_000351 | NP_033403 | |||||||||||
| 基因位置 |
Chr 11: 2.14 – 2.15 Mb |
Chr 7: 142.7 – 142.71 Mb | |||||||||||
| PubMed查询 | [1] | [2] | |||||||||||
反应
此加氧酶被发现于所有含儿茶酚胺的细胞溶质中。此起始步骤是产生儿茶酚胺的限速步骤。
此酶有高度地特异性，不会接受吲哚的衍生物——这一点与许多其他涉及到产生儿茶酚胺的酶不同。
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临床意义
酪氨酸羟化酶可以被药物α-甲基-对-酪氨酸（甲基酪氨酸）所抑制。此抑制作用可以导致脑部多巴胺与去甲肾上腺素的消耗，这是因为缺乏前体L-多巴（L-3,4-二羟基苯丙氨酸），此物质可以由酪氨酸羟化酶所合成。此药很少被使用并会导致抑郁，但它在治疗嗜铬细胞瘤以及抗高血压方面很有用处。
在自體免疫性多内分泌腺病综合征（APS）I型中，酪氨酸羟化酶是一个自身抗原[3]。
参考文献
- ^ Kaufman S. Tyrosine hydroxylase. Adv. Enzymol. Relat. Areas Mol. Biol. 1995, 70: 103–220. PMID 8638482. doi:10.1002/9780470123164.ch3.
- ^ 2.0 2.1 Nagatsu T. Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Essays Biochem. 1995, 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. Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I. Biochem. Biophys. Res. Commun. January 2000, 267 (1): 456–61. PMID 10623641. doi:10.1006/bbrc.1999.1945.
- ^ Ono M, Okamoto M, Kawabe N, Umezawa H, Takeuchi T. Oudenone, a novel tyrosine hydroxylase inhibitor from microbial origin. J. Am. Chem. Soc. March 1971, 93 (5): 1285–6. PMID 5545929. doi:10.1021/ja00734a054.
- ^ Ayukawa S, Takeuchi T, Sezaki M, Hara T, Umezawa H. Inhibition of tyrosine hydroxylase by aquayamycin. J. Antibiot. May 1968, 21 (5): 350–3. PMID 5726288.
深入阅读
- Masserano JM, Weiner N. Tyrosine hydroxylase regulation in the central nervous system.. Mol. Cell. Biochem. 1983, 53–54 (1-2): 129–52. PMID 6137760. doi:10.1007/BF00225250.
- Meloni R, Biguet NF, Mallet J. 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. 2002, 26 (2-3): 389–403. PMID 12428766. doi:10.1385/MN:26:2-3:389.
- Joh TH, Park DH, Reis DJ. Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation.. Proc. Natl. Acad. Sci. U.S.A. 1979, 75 (10): 4744–8. PMC 336196
. PMID 33381. doi:10.1073/pnas.75.10.4744. - Haycock JW, Ahn NG, Cobb MH, Krebs EG. 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. 1992, 89 (6): 2365–9. PMC 48658 . PMID 1347949. doi:10.1073/pnas.89.6.2365.
- Haycock JW. Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40.. J. Biol. Chem. 1990, 265 (20): 11682–91. PMID 1973163.
- Craig SP, Buckle VJ, Lamouroux A; et al. Localization of the human tyrosine hydroxylase gene to 11p15: gene duplication and evolution of metabolic pathways.. Cytogenet. Cell Genet. 1986, 42 (1-2): 29–32. PMID 2872999. doi:10.1159/000132246.
- Grima B, Lamouroux A, Boni C; et al. A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics.. Nature. 1987, 326 (6114): 707–11. PMID 2882428. doi:10.1038/326707a0.
- Kaneda N, Kobayashi K, Ichinose H; et al. 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. 1987, 146 (3): 971–5. PMID 2887169. doi:10.1016/0006-291X(87)90742-X.
- Kobayashi K, Kaneda N, Ichinose H; et al. Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3.. Nucleic Acids Res. 1987, 15 (16): 6733. PMC 306135 . PMID 2888085. doi:10.1093/nar/15.16.6733.
- O'Malley KL, Anhalt MJ, Martin BM; et al. Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs.. Biochemistry. 1988, 26 (22): 6910–4. PMID 2892528. doi:10.1021/bi00396a007.
- Le Bourdellès B, Boularand S, Boni C; et al. Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms.. J. Neurochem. 1988, 50 (3): 988–91. PMID 2892893. doi:10.1111/j.1471-4159.1988.tb03009.x.
- Ginns EI, Rehavi M, Martin BM; et al. Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector.. J. Biol. Chem. 1988, 263 (15): 7406–10. PMID 2896667.
- Kobayashi K, Kaneda N, Ichinose H; et al. Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types.. J. Biochem. 1988, 103 (6): 907–12. PMID 2902075.
- Coker GT, Vinnedge L, O'Malley KL. Characterization of rat and human tyrosine hydroxylase genes: functional expression of both promoters in neuronal and non-neuronal cell types.. Biochem. Biophys. Res. Commun. 1989, 157 (3): 1341–7. PMID 2905129. doi:10.1016/S0006-291X(88)81022-2.
- Vulliet PR, Woodgett JR, Cohen P. Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase.. J. Biol. Chem. 1984, 259 (22): 13680–3. PMID 6150037.
- Zhou QY, Quaife CJ, Palmiter RD. Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development.. Nature. 1995, 374 (6523): 640–3. PMID 7715703. doi:10.1038/374640a0.
- Lüdecke B, Bartholomé K. Frequent sequence variant in the human tyrosine hydroxylase gene.. Hum. Genet. 1995, 95 (6): 716. PMID 7789962. doi:10.1007/BF00209496.
- Lüdecke B, Dworniczak B, Bartholomé K. A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome.. Hum. Genet. 1995, 95 (1): 123–5. PMID 7814018. doi:10.1007/BF00225091.
- Knappskog PM, Flatmark T, Mallet J; et al. Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.. Hum. Mol. Genet. 1996, 4 (7): 1209–12. PMID 8528210. doi:10.1093/hmg/4.7.1209.
