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:
- L-色氨酸 + 四氢生物蝶呤 + O2 5-羟色氨酸 + 二氢生物蝶呤 + H2O
Quick Facts 色氨酸5-单加氧酶, 命名 ...
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Quick Facts 色氨酸羟化酶1(色氨酸5-单加氧酶), 识别 ...
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Quick Facts 色氨酸羟化酶2, 识别 ...
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以上反应还需要亚铁离子作为辅酶。
色氨酸
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5-羟色氨酸
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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。
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]
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.
- 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.