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{{enzyme | Name = 色氨酸5-单加氧酶 | Systematic_name = <small>L</small>-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating) | EC_number = 1.14.16.4 | Acronym = TPH | Other_names = <small>L</small>-tryptophan hydroxylase; indoleacetic acid-5-hydroxylase; tryptophan 5-hydroxylase; tryptophan hydroxylase | CAS_number = 9037-21-2 | IUBMB_EC_number = 1/14/16/4 | GO_code = 0004510 | image = | width = | caption = }} {{protein | Name = 色氨酸羟化酶1(色氨酸5-单加氧酶) | caption = | image = | width = | HGNCid = 12008 | Symbol = [[TPH1]] | AltSymbols = TPRH, TPH | EntrezGene = 7166 | OMIM = 191060 | RefSeq = NM_004179 | UniProt = P17752 | PDB = 1MLW | ECnumber = 1.14.16.4 | Chromosome = 11 | Arm = p | Band = 15.3 | LocusSupplementaryData = -p14 }} {{protein | Name = 色氨酸羟化酶2 | caption = | image = | width = | HGNCid = 20692 | Symbol = [[TPH2]] | AltSymbols = | EntrezGene = 121278 | OMIM = 607478 | RefSeq = NM_173353 | UniProt = Q8IWU9 | PDB = | ECnumber = | Chromosome = 12 | Arm = q | Band = 15 | LocusSupplementaryData = }} '''色氨酸羟化酶'''({{lang-en|Tryptophan hydroxylase}},[[EC编号|EC]] [http://enzyme.expasy.org/EC/1.14.16.4 1.14.16.4] {{Wayback|url=http://enzyme.expasy.org/EC/1.14.16.4 |date=20201127150939 }})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]] + O<sub>2</sub> <math>\rightleftharpoons</math> [[5-羟色氨酸]] + [[二氢生物蝶呤]] + H<sub>2</sub>O 以上反应还需要[[亚铁离子]]作为[[辅酶]]。 == 功能 == {{stack| {{Enzymatic Reaction |foward_enzyme=色氨酸羟化酶 |reverse_enzyme= |substrate=[[色氨酸]] |product=[[5-羟色氨酸]] |reaction_direction_(forward/reversible/reverse)=forward |minor_foward_substrate(s)=O<sub>2</sub><br />[[四氢生物蝶呤|BH<sub>4</sub>]] |minor_foward_product(s)=H<sub>2</sub>O<br />BH<sub>2</sub> |minor_reverse_substrate(s)= |minor_reverse_product(s)= |substrate_image=Tryptophan_simple.png |substrate_image_size=120px |product_image=5-hydroxytryptophan.png |product_image_size=120px }} }} 色氨酸羟化酶可以使[[色氨酸]]的C<sub>5</sub>[[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。<ref name="pmid11747434">{{cite journal | author = McKinney J, Teigen K, Frøystein NA, Salaün C, Knappskog PM, Haavik J, Martínez A | title = Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity | journal = Biochemistry | volume = 40 | issue = 51 | pages = 15591–601 | pmid = 11747434 | doi = 10.1021/bi015722x | url = http://www.bh4.org/pdf/mckinney.pdf | date = December 2001 | deadurl = yes | archiveurl = https://web.archive.org/web/20081217045622/http://www.bh4.org/pdf/mckinney.pdf | archivedate = 2008-12-17 }}</ref>与酪氨酸羟化酶、苯丙氨酸羟化酶类似,色氨酸羟化酶也以(6''R'')-<small>L</small>-赤型-5,6,7,8-[[四氢生物蝶呤]](BH<sub>4</sub>)及[[双氧]](O<sub>2</sub>)作为氧化还原的底物。<ref name="urlBH4 Databases">{{cite web| url =http://www.bh4.org/BH4_Deficiency_Biochemistry.asp| title =tetrahydrobiopterin| author =| authorlink =| coauthors =| year =2005| format =| work =BH4 Databases| publisher =BH4.org| pages =| language =| archiveurl =https://web.archive.org/web/20061206195735/http://bh4.org/BH4_Deficiency_Biochemistry.asp| archivedate =2006-12-06| quote =| accessdate =| deadurl =yes}}</ref> [[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]]。<ref name="pmid12379098">{{cite journal | author = Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC | title = Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin | journal = Biochemistry | volume = 41 | issue = 42 | pages = 12569–74 | pmid = 12379098 | doi = 10.1021/bi026561f | url = |date=October 2002}}</ref> 色氨酸羟化酶的[[酶活性]](即色氨酸羟化酶将<small>L</small>-色氨酸转化为5-羟色胺[[前体]]<small>L</small>-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 (人类)|11号染色体]]和[[12号染色体 (人类)|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%。<ref name="pmid14563478">{{cite journal | author = Walther DJ, Bader M | title = A unique central tryptophan hydroxylase isoform | journal = Biochem. Pharmacol. | volume = 66 | issue = 9 | pages = 1673–80 | pmid = 14563478 | doi = 10.1016/S0006-2952(03)00556-2| url = |date=November 2003}}</ref> *TPH1主要[[基因表达|表达]]在分泌5-羟色胺的[[组织 (生物学)|组织]]中,如[[皮肤]]、[[肠 (解剖学)|肠道]]、[[松果体]]以及[[中枢神经系统]]中。 *TPH2则仅在[[神经细胞]]中表达,且其于中枢神经系统中的表达量较TPH1大。 == 参考文献 == <references/> == 扩展阅读 == {{refbegin | 2}} * {{cite journal | author = Friedman PA, Kappelman AH, Kaufman S | year = 1972 | title = Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain | journal = J. Biol. Chem. | volume = 247 | pages = 4165–73 | pmid = 4402511 | issue = 13 }} * {{cite journal | author = Hamon M, Bourgoin S, Artaud F, Glowinski J | year = 1979 | title = 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 | journal = J. Neurochem. | volume = 33 | pages = 1031–42 | pmid = 315449 | doi = 10.1111/j.1471-4159.1979.tb05239.x | issue = 5 }} * {{cite journal | author = Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O | year = 1970 | title = Enzymic studies on the biosynthesis of serotonin in mammalian brain | journal = J. Biol. Chem. | volume = 245 | pages = 1699–709 | pmid = 5309585 | issue = 7 }} * {{cite journal | author = Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A | year = 1969 | title = Further studies on tryptophan hydroxylase in rat brainstem and beef pineal | journal = Biochem. Pharmacol. | volume = 18 | pages = 1071–81 | pmid = 5789774 | doi = 10.1016/0006-2952(69)90111-7 | issue = 5 }} * {{cite journal | author = Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC | year = 2002 | title = Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin | journal = Biochemistry. | volume = 41 | pages = 12569–74 | pmid = 12379098 | doi = 10.1021/bi026561f | issue = 42 }} * {{cite journal | author = Windahl MS, Petersen CR, Christensen, HEM, Harris P | year = 2008 | title = Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate | journal = Biochemistry. | volume = 47 | pages = 12087–94 | pmid = 18937498 | doi = 10.1021/bi8015263 | issue = 46}} {{refend}} {{双加氧酶}} {{神经递质代谢酶类}} [[Category:酶]] [[Category:EC 1.14.16]]
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