色氨酸羥化酶
色氨酸羥化酶(英語:Tryptophan hydroxylase,EC 1.14.16.4 (頁面存檔備份,存於網際網路檔案館))也稱為色氨酸5-單加氧酶,簡稱TPH,是合成神經遞質5-羥色胺的過程中重要的酶。色氨酸羥化酶可催化如下酶促反應:
色氨酸5-單加氧酶 | |||||||||
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識別碼 | |||||||||
EC編號 | 1.14.16.4 | ||||||||
CAS號 | 9037-21-2 | ||||||||
數據庫 | |||||||||
IntEnz | IntEnz瀏覽 | ||||||||
BRENDA | BRENDA入口 | ||||||||
ExPASy | NiceZyme瀏覽 | ||||||||
KEGG | KEGG入口 | ||||||||
MetaCyc | 代謝路徑 | ||||||||
PRIAM | 概述 | ||||||||
PDB | RCSB PDB PDBj PDBe PDBsum | ||||||||
基因本體 | AmiGO / EGO | ||||||||
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色氨酸羥化酶1(色氨酸5-單加氧酶) | |
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識別 | |
符號 | TPH1 |
替換符號 | TPRH, TPH |
Entrez | 7166 |
HUGO | 12008 |
OMIM | 191060 |
PDB | 1MLW |
RefSeq | NM_004179 |
UniProt | P17752 |
其他資料 | |
EC編號 | 1.14.16.4 |
基因座 | 11 p15.3-p14 |
色氨酸羥化酶2 | |
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識別 | |
符號 | TPH2 |
Entrez | 121278 |
HUGO | 20692 |
OMIM | 607478 |
RefSeq | NM_173353 |
UniProt | Q8IWU9 |
其他資料 | |
基因座 | 12 q15 |
功能
色氨酸羥化酶可以使色氨酸的C5羥基化,使色氨酸轉化為5-羥色氨酸(5-HTP)。這一催化氧化反應是神經遞質5-羥色胺生物合成過程中的啟示步及限速步。色氨酸羥化酶也是褪黑素生物合成過程中需要用到的第一種酶。
色氨酸羥化酶(TPH)與酪氨酸羥化酶(TH)、苯丙氨酸羥化酶(PAH)等皆為芳香族氨基酸羥化酶超家族(superfamily)的成員,負責催化重要代謝途徑中的關鍵步驟。[1]與酪氨酸羥化酶、苯丙氨酸羥化酶類似,色氨酸羥化酶也以(6R)-L-赤型-5,6,7,8-四氫生物蝶呤(BH4)及雙氧(O2)作為氧化還原的底物。[2]
人類的色氨酸羥化酶若受到某些物質(如對氯苯丙氨酸)的抑制,可能會引發抑鬱症。[3]
色氨酸羥化酶的酶活性(即色氨酸羥化酶將L-色氨酸轉化為5-羥色胺前體L-5-羥色氨酸的反應速率)可以在被蛋白激酶A等激酶催化磷酸化後增加。
異構體
哺乳動物都擁有兩種不同的TPH基因。人類的兩個TPH基因分別位於11號染色體和12號染色體上,它們編碼着不同卻同源的酶——TPH1及TPH2,這兩種基因的序列一致性達71%。[4]
參考文獻
- ^ 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. (原始內容 (PDF)存檔於2008-12-17).
- ^ tetrahydrobiopterin. BH4 Databases. BH4.org. 2005. (原始內容存檔於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.
擴展閱讀
- 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.