色氨酸羟化酶
色氨酸羟化酶（英语：Tryptophan hydroxylase，EC 1.14.16.4 （页面存档备份，存于互联网档案馆））也称为色氨酸5-单加氧酶，简称TPH，是合成神经递质5-羟色胺的过程中重要的酶。色氨酸羟化酶可催化如下酶促反应：
| 色氨酸5-单加氧酶 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| 识别码 | |||||||||
| EC编号 | 1.14.16.4 | ||||||||
| CAS号 | 9037-21-2 | ||||||||
| 数据库 | |||||||||
| IntEnz | IntEnz浏览 | ||||||||
| BRENDA | BRENDA入口 | ||||||||
| ExPASy | NiceZyme浏览 | ||||||||
| KEGG | KEGG入口 | ||||||||
| MetaCyc | 代谢路径 | ||||||||
| PRIAM | 概述 | ||||||||
| PDB | RCSB PDB PDBj PDBe PDBsum | ||||||||
| 基因本体 | AmiGO / EGO | ||||||||
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| 色氨酸羟化酶1（色氨酸5-单加氧酶） | |
|---|---|
| 识别 | |
| 符号 | TPH1 |
| 替换符号 | TPRH, TPH |
| Entrez | 7166 |
| HUGO | 12008 |
| OMIM | 191060 |
| PDB | 1MLW |
| RefSeq | NM_004179 |
| UniProt | P17752 |
| 其他资料 | |
| EC编号 | 1.14.16.4 |
| 基因座 | 11 p15.3-p14 |
| 色氨酸羟化酶2 | |
|---|---|
| 识别 | |
| 符号 | TPH2 |
| Entrez | 121278 |
| HUGO | 20692 |
| OMIM | 607478 |
| RefSeq | NM_173353 |
| UniProt | Q8IWU9 |
| 其他资料 | |
| 基因座 | 12 q15 |
功能
色氨酸羟化酶可以使色氨酸的C5羟基化，使色氨酸转化为5-羟色氨酸（5-HTP）。这一催化氧化反应是神经递质5-羟色胺生物合成过程中的启示步及限速步。色氨酸羟化酶也是褪黑素生物合成过程中需要用到的第一种酶。
色氨酸羟化酶（TPH）与酪氨酸羟化酶（TH）、苯丙氨酸羟化酶（PAH）等皆为芳香族氨基酸羟化酶超家族（superfamily）的成员，负责催化重要代谢途径中的关键步骤。[1]与酪氨酸羟化酶、苯丙氨酸羟化酶类似，色氨酸羟化酶也以(6R)-L-赤型-5,6,7,8-四氢生物蝶呤（BH4）及双氧（O2）作为氧化还原的底物。[2]
人类的色氨酸羟化酶若受到某些物质（如对氯苯丙氨酸）的抑制，可能会引发抑郁症。[3]
色氨酸羟化酶的酶活性（即色氨酸羟化酶将L-色氨酸转化为5-羟色胺前体L-5-羟色氨酸的反应速率）可以在被蛋白激酶A等激酶催化磷酸化后增加。
异构体
哺乳动物都拥有两种不同的TPH基因。人类的两个TPH基因分别位于11号染色体和12号染色体上，它们编码着不同却同源的酶——TPH1及TPH2，这两种基因的序列一致性达71%。[4]
参考文献
- ^ McKinney J, Teigen K, Frøystein NA, Salaün C, Knappskog PM, Haavik J, Martínez A. Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity (PDF). Biochemistry. December 2001, 40 (51): 15591–601. PMID 11747434. doi:10.1021/bi015722x. （原始内容 (PDF)存档于2008-12-17）.
- ^ tetrahydrobiopterin. BH4 Databases. BH4.org. 2005. （原始内容存档于2006-12-06）.
- ^ Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry. October 2002, 41 (42): 12569–74. PMID 12379098. doi:10.1021/bi026561f.
- ^ Walther DJ, Bader M. A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. November 2003, 66 (9): 1673–80. PMID 14563478. doi:10.1016/S0006-2952(03)00556-2.
扩展阅读
- Friedman PA, Kappelman AH, Kaufman S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J. Biol. Chem. 1972, 247 (13): 4165–73. PMID 4402511.
- Hamon M, Bourgoin S, Artaud F, Glowinski J. The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium. J. Neurochem. 1979, 33 (5): 1031–42. PMID 315449. doi:10.1111/j.1471-4159.1979.tb05239.x.
- Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O. Enzymic studies on the biosynthesis of serotonin in mammalian brain. J. Biol. Chem. 1970, 245 (7): 1699–709. PMID 5309585.
- Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A. Further studies on tryptophan hydroxylase in rat brainstem and beef pineal. Biochem. Pharmacol. 1969, 18 (5): 1071–81. PMID 5789774. doi:10.1016/0006-2952(69)90111-7.
- Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC. Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin. Biochemistry. 2002, 41 (42): 12569–74. PMID 12379098. doi:10.1021/bi026561f.
- Windahl MS, Petersen CR, Christensen, HEM, Harris P. Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate. Biochemistry. 2008, 47 (46): 12087–94. PMID 18937498. doi:10.1021/bi8015263.