KEGG   ENZYME: 1.14.16.4
Entry
EC 1.14.16.4                Enzyme                                 
Name
tryptophan 5-monooxygenase;
L-tryptophan hydroxylase;
indoleacetic acid-5-hydroxylase;
tryptophan 5-hydroxylase;
tryptophan hydroxylase
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced pteridine as one donor, and incorporation of one atom of oxygen into the other donor
Sysname
L-tryptophan,tetrahydropteridine:oxygen oxidoreductase (5-hydroxylating)
Reaction(IUBMB)
L-tryptophan + a 5,6,7,8-tetrahydropteridine + O2 = 5-hydroxy-L-tryptophan + a 4a-hydroxy-5,6,7,8-tetrahydropteridine [RN:R12542]
Reaction(KEGG)
R12542;
(other) R01814 R07213
Substrate
L-tryptophan [CPD:C00078];
5,6,7,8-tetrahydropteridine [CPD:C05650];
O2 [CPD:C00007]
Product
5-hydroxy-L-tryptophan [CPD:C00643];
4a-hydroxy-5,6,7,8-tetrahydropteridine [CPD:C22239]
Comment
The active centre contains mononuclear iron(II). The enzyme is activated by phosphorylation, catalysed by a Ca2+-activated protein kinase. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
History
EC 1.14.16.4 created 1972, modified 2003, modified 2019
Pathway
ec00380  Tryptophan metabolism
ec00790  Folate biosynthesis
ec01100  Metabolic pathways
Orthology
K00502  tryptophan 5-monooxygenase
Genes
HSA: 121278(TPH2) 7166(TPH1)
PTR: 466453(TPH1) 467070(TPH2)
PPS: 100977344(TPH2) 103782654(TPH1)
GGO: 101132108(TPH1) 101146582(TPH2)
PON: 100459809(TPH2) 103891844(TPH1)
NLE: 100588345(TPH2) 100601780(TPH1)
MCC: 664730(TPH2) 695363(TPH1)
MCF: 102124167(TPH2) 102145077(TPH1)
CSAB: 103238730(TPH2) 103239320(TPH1)
CATY: 105581034(TPH2) 105598886(TPH1)
PANU: 101001223(TPH2) 103875499(TPH1)
TGE: 112606866(TPH1) 112635076(TPH2)
RRO: 104667637(TPH1) 104668095(TPH2)
RBB: 108526665(TPH2) 108528377(TPH1)
TFN: 117081781(TPH1) 117089733(TPH2)
PTEH: 111552365(TPH2) 111555044(TPH1)
CJC: 100403096(TPH2) 100415029(TPH1)
SBQ: 101051709(TPH2) 104652952(TPH1)
CSYR: 103257543(TPH2) 103265117(TPH1)
MMUR: 105856884(TPH2) 105879970(TPH1)
OGA: 100953596(TPH2) 105886446(TPH1)
MMU: 216343(Tph2) 21990(Tph1)
MCAL: 110298535(Tph1) 110303601(Tph2)
MPAH: 110326744(Tph2) 110330199(Tph1)
RNO: 24848(Tph1) 317675(Tph2)
MCOC: 116076348(Tph2) 116102248(Tph1)
MUN: 110550489(Tph1) 110555372(Tph2)
CGE: 100763947(Tph2) 100767923(Tph1)
PLEU: 114699018(Tph2) 114700529(Tph1)
NGI: 103734460(Tph1) 103735331(Tph2)
HGL: 101710219(Tph1) 101714361(Tph2)
CPOC: 100718189(Tph1) 100724594(Tph2)
CCAN: 109679995(Tph1)
DORD: 105988605(Tph2) 105999169(Tph1)
DSP: 122117778(Tph1) 122124215(Tph2)
OCU: 100009100(TPH1) 100101558(TPH1) 100344397(TPH2)
OPI: 101517264(TPH1) 101524788(TPH2)
TUP: 102481223(TPH2) 102487889(TPH1)
CFA: 481165(TPH2) 611956(TPH1)
VVP: 112922180(TPH2) 112927027(TPH1)
VLG: 121476514(TPH1) 121491914(TPH2)
AML: 100467699(TPH1) 100472165(TPH2)
UMR: 103656892(TPH2) 103679407(TPH1)
UAH: 113246602(TPH1) 113256261(TPH2)
UAR: 123787118(TPH2) 123791643(TPH1)
ELK: 111142174 111150060
MPUF: 101678853(TPH2) 101685595(TPH1)
ORO: 101364741(TPH1) 101369839(TPH2)
EJU: 114202737 114202738 114219387(TPH1)
ZCA: 113914718(TPH1) 113922464(TPH2) 113933908
MLX: 118004319(TPH1) 118008557(TPH2)
FCA: 101082165(TPH2) 101098575(TPH1)
PYU: 121040737(TPH2) 121043698(TPH1)
PBG: 122474068(TPH2) 122484410(TPH1)
PTG: 102948910(TPH2) 102969936(TPH1)
PPAD: 109270520(TPH2) 109271211(TPH1)
AJU: 106967384(TPH2) 106977480(TPH1)
HHV: 120223353(TPH2) 120234792(TPH1)
BTA: 100336620(TPH2) 781941(TPH1)
BOM: 102269915(TPH1) 102275621(TPH2)
BIU: 109558652(TPH2) 109569943(TPH1)
BBUB: 102396992(TPH2) 102411029(TPH1)
CHX: 102174722(TPH2) 102184739(TPH1)
OAS: 101113620(TPH1) 101120314(TPH2)
ODA: 120857959(TPH2) 120876397(TPH1)
CCAD: 122427666(TPH2) 122450434(TPH1)
SSC: 100511002(TPH1) 100627725(TPH2)
CFR: 102512650(TPH2) 102522464(TPH1)
CBAI: 105072045(TPH2) 105076585(TPH1)
CDK: 105086665(TPH1) 105095994(TPH2)
BACU: 102997866(TPH1) 103006656(TPH2)
LVE: 103083324(TPH1) 103087968(TPH2)
OOR: 101271217(TPH2) 101273510(TPH1)
DLE: 111165253(TPH1) 111173732(TPH2)
PCAD: 102985446(TPH2) 102994832(TPH1)
PSIU: 116758349(TPH1) 116761326(TPH2)
ECB: 100009684(TPH2) 100056614(TPH1)
EPZ: 103559190(TPH1) 103561950(TPH2)
EAI: 106826108(TPH2) 106835485(TPH1)
MYB: 102241626(TPH2) 102244804(TPH1)
MYD: 102753485(TPH2) 102767513(TPH1)
MMYO: 118651936(TPH2) 118663522(TPH1)
MLF: 102418890(TPH1) 102434305(TPH2)
MNA: 107526733(TPH2) 107546725(TPH1)
PKL: 118712480(TPH1) 118730418(TPH2)
HAI: 109387680(TPH2) 109388096(TPH1)
DRO: 112303363(TPH1) 112319064(TPH2)
SHON: 118989337(TPH2) 118989705(TPH1)
AJM: 119053091(TPH1) 119055866
PDIC: 114499999(TPH1) 114513219(TPH2)
PHAS: 123810024(TPH1) 123812692(TPH2)
MMF: 118624020(TPH2) 118628186(TPH1)
RFQ: 117028733(TPH2) 117030182(TPH1)
PALE: 102882683(TPH1) 102891331(TPH2)
PGIG: 120593610(TPH1) 120605080(TPH2)
PVP: 105301629(TPH2) 105304216(TPH1)
RAY: 107508027(TPH1) 107512624(TPH2)
MJV: 108400665(TPH2) 108404860(TPH1)
TOD: 119248285(TPH2) 119254591(TPH1)
SARA: 101549071(TPH1) 101551893(TPH2)
LAV: 100658860(TPH1) 100669911(TPH2)
TMU: 101355042 101360632
DNM: 101414982(TPH2) 101440944(TPH1)
MDO: 100011937(TPH2) 100020009(TPH1)
GAS: 123250170(TPH2) 123251417(TPH1)
SHR: 100915442(TPH1) 100923184(TPH2)
PCW: 110195961(TPH2) 110221097(TPH1)
OAA: 100079349(TPH2) 100090381(TPH1)
GGA: 395799(TPH1) 408026(TPH2)
PCOC: 116226749(TPH2) 116242903(TPH1)
MGP: 100303678(TPH2) 100549515(TPH1)
CJO: 107310284(TPH2) 107314681(TPH1)
NMEL: 110392823(TPH2) 110401279(TPH1)
APLA: 101793780(TPH2) 101797806(TPH1)
ACYG: 106042627 106046728(TPH2)
AFUL: 116490046(TPH1) 116495542(TPH2)
TGU: 100228542(TPH2) 100229598(TPH1)
LSR: 110468084(TPH1) 110469834(TPH2)
SCAN: 103813668(TPH2) 103826774(TPH1)
PMOA: 120499841(TPH2) 120501148(TPH1)
OTC: 121339484(TPH2) 121341539(TPH1)
PRUF: 121352558(TPH2) 121360970(TPH1)
GFR: 102036017(TPH2) 102041307(TPH1)
FAB: 101817911(TPH2) 101820220(TPH1)
PHI: 102103962(TPH2) 102106431(TPH1)
PMAJ: 107204683(TPH2) 107205260(TPH1)
CCAE: 111930805(TPH1) 111937577(TPH2)
CCW: 104685325(TPH1) 104698473(TPH2)
ETL: 114059440(TPH1) 114059989(TPH2)
ZAB: 102063944(TPH1) 102067699(TPH2)
FPG: 101914983(TPH1) 101918183(TPH2)
FCH: 102052919(TPH2) 102057315(TPH1)
CLV: 102092014(TPH2) 102095810(TPH1)
EGZ: 104123206(TPH1) 104132957(TPH2)
NNI: 104010591(TPH1) 104011038(TPH2)
ACUN: 113481125(TPH1) 113489370(TPH2)
TALA: 104356202(TPH1) 104369069(TPH2)
PADL: 103920030(TPH2) 103920766(TPH1)
ACHC: 115336364(TPH2) 115352028(TPH1)
AAM: 106488161(TPH2) 106497047(TPH1)
AROW: 112964095(TPH2) 112972385(TPH1)
NPD: 112951457(TPH1) 112958850(TPH2)
DNE: 112978923(TPH1) 112983291(TPH2)
ASN: 102376121(TPH2) 102380987(TPH1)
AMJ: 102560538(TPH1) 102572294(TPH2)
CPOO: 109315970(TPH2) 109321541(TPH1)
GGN: 109297011(TPH2) 109299139(TPH1)
PSS: 102445658(TPH2) 102460535(TPH1)
CMY: 102930035(TPH2) 102934830(TPH1)
CPIC: 101933912(TPH2) 101948172(TPH1)
TST: 117877260(TPH1) 117877915(TPH2)
CABI: 116817165(TPH2) 116838939(TPH1)
MRV: 120383209(TPH2) 120402771(TPH1)
ACS: 100562860(tph1) 100564918(tph2)
PVT: 110084890(TPH2) 110088804(TPH1)
SUND: 121929851(TPH1) 121931396(TPH2)
PBI: 103048564(TPH1) 103062013
PMUR: 107283841(TPH2) 107296796(TPH1)
TSR: 106541682(TPH2) 106552357
PGUT: 117655482(TPH2) 117665266(TPH1)
VKO: 123021233(TPH1) 123033286(TPH2)
PMUA: 114598774(TPH1) 114605959(TPH2)
ZVI: 118089013(TPH1) 118090812(TPH2)
GJA: 107115340(TPH2) 107115550(TPH1)
XLA: 108710258 108713144(tph2.S) 387560(tph1.L)
XTR: 100486097(tph2) 100497239(tph1)
NPR: 108785999(TPH1) 108788312(TPH2)
RTEM: 120917010(TPH1) 120931964(TPH2)
BBUF: 120980604(TPH1) 120980734(TPH2)
BGAR: 122920144(TPH1) 122925790(TPH2)
DRE: 352943(tph1a) 407712(tph2) 415103(tph1b)
SRX: 107720785(tph1) 107740327 107740493 107749937 107750725 107755016
SANH: 107663941 107670227 107672314 107673292 107686260 107700369
SGH: 107553080 107557706 107559977 107564603 107569655 107583800
CCAR: 109074194 109086690 109110720
CAUA: 113043713 113052380 113066434 113105990 113118311
IPU: 108259139(tph1b) 108263971(tph2) 108274454(tph1a) 124626828
PHYP: 113529905(tph1) 113534273 113540934
SMEO: 124379583(tph1b) 124392964(tph1a) 124395690(tph2)
AMEX: 103025693 103043966(tph1) 103046451
EEE: 113582098 113582294 113584487(tph1)
TRU: 446047(tph1) 446048(tph2)
TNG: GSTEN00006938G001
LCO: 104921438 104932027(tph1) 104938290
NCC: 104964502(tph1) 104965427
CGOB: 115004781 115009666(tph1)
ELY: 117257841 117261799(tph1a) 117261880(tph2)
PLEP: 121943098 121950084(tph1a)
SLUC: 116038510(tph1a) 116061876(tph2) 116067391
ECRA: 117947847 117949802(tph1a)
PFLV: 114557592 114559910(tph1) 114560174(tph2)
GAT: 120808697(tph1a) 120809623(tph2) 120833009
PPUG: 119195577(tph2) 119196279(tph1a) 119229676
MSAM: 119889771 119893900 119894244(tph2)
CUD: 121515571(tph2) 121515765(tph1a)
MZE: 101480764(tph2) 101484460 101486409(tph1)
ONL: 100691623(tph1) 100694382 100696141
OAU: 116311354(tph2) 116319109 116326748(tph1a)
OLA: 101166957(tph2) 101170994 101175562(tph1)
OML: 112141172 112152292(tph1a) 112161307
XMA: 102216868(tph1) 102234879 102236889(tph2)
XCO: 114142506 114150104(tph2) 114151044(tph1)
XHE: 116710961(tph2) 116718124 116729036(tph1)
PRET: 103462259 103466377(tph2) 103466482(tph1)
PFOR: 103130852 103149204 103156520(tph1)
PLAI: 106942220 106947747(tph1) 106959120
PMEI: 106905963(tph2) 106925763 106933112(tph1)
GAF: 122835380(tph1a) 122836199(tph2) 122846231
CVG: 107099807(tph2) 107101475 107103791(tph1)
CTUL: 119773716 119781658(tph2) 119787407(tph1a)
NFU: 107381938 107388661(tph1) 107389098(tph2)
KMR: 108229864(tph1a) 108237877 108251439(tph2)
ALIM: 106516735 106521168(tph1) 106531022(tph2)
NWH: 119415797(tph1a) 119416121(tph2) 119423870
AOCE: 111578292 111584097(tph1)
CSEM: 103379608(tph2) 103380212(tph1)
POV: 109624178(tph1) 109644721
SSEN: 122775398(tph2) 122776545(tph1a)
HHIP: 117762606(tph1a) 117762648(tph2)
LCF: 108876698(tph1) 108891738(tph2)
SDU: 111229584(tph1) 111233710(tph2)
SLAL: 111648930 111667055(tph1)
XGL: 120793262(tph2) 120793556(tph1a)
HCQ: 109507516(tph1) 109518199(tph2) 109529786
BPEC: 110162577 110168313(tph2) 110169358(tph1)
MALB: 109951036(tph1) 109969076(tph2)
SASA: 106561539 106562311 106584760 106587468
OTW: 112218837(tph2) 112236633 112237058(tph1a) 112249279
OMY: 110499357(tph2) 110506638 110521183(tph1a) 110526507
OGO: 124033100 124033744(tph2) 124035648 124037467(tph1a)
ONE: 115111128 115113690 115126650 115133981
SALP: 111962707 111969461 111974702 112073037
SNH: 120025196 120051724(tph1a) 120056450 120066714(tph2)
ELS: 105018201(tph1) 105018238(tph2)
SFM: 108936426(tph2) 108941264 108942210
PKI: 111834510 111835440 111851447(tph2)
AANG: 118214860 118219170(tph2) 118227486
LOC: 102682173(tph2) 102697783(tph1)
PSPA: 121294421 121318037 121320056 121330423(tph1a)
ARUT: 117415915 117419550 117432389 117434745(tph1a)
LCM: 102362567(TPH1) 102363250(TPH2)
CMK: 103174831 103185330
RTP: 109927655 109935866
BFO: 118406289 118406966
BBEL: 109480215
CIN: 100049066
SCLV: 120335756
SPU: 115922565 578903
APLC: 110981081
SKO: 100329006(tph-1)
DME: Dmel_CG9122(Trh)
DER: 6543860
DSE: 6610268
DSI: Dsimw501_GD13494(Dsim_GD13494)
DYA: Dyak_GE20982
DAN: 6492953
DSR: 110178615
DPO: Dpse_GA21560
DPE: 6603951
DMN: 108153552
DWI: 6639428
DGR: 6558602
DMO: Dmoj_GI12709
DAZ: 108614428
DNV: 108651306
DHE: 111600458
DVI: 6623307
CCAT: 101460734
BOD: 106622704
MDE: 101893101
SCAC: 106092589
LCQ: 111676820
AGA: AgaP_AGAP006020
ACOZ: 120952581
AARA: 120896557
AAG: 23687540
AALB: 109413958
CQU: CpipJ_CPIJ019741
CPII: 120412891
CNS: 116345266
AME: 411200
ACER: 108003440
ALAB: 122716618
BIM: 100742465
BBIF: 117204398
BVK: 117233459
BVAN: 117153441
BTER: 100647460
BPYO: 122569193
CCAL: 108624633
OBB: 114876888
MGEN: 117223613
NMEA: 116424137
CGIG: 122395229
SOC: 105194454
MPHA: 105839937
AEC: 105145053
ACEP: 105619346
PBAR: 105430282
VEM: 105567116
HST: 105182103
DQU: 106750935
CFO: 105251016
FEX: 115233862
LHU: 105678051
PGC: 109861523
OBO: 105279028
PCF: 106791737
PFUC: 122524389
VPS: 122634219
NVI: 100123183
CSOL: 105363200
TPRE: 106653657
MDL: 103579283
CGLO: 123267565
FAS: 105264297
DAM: 107046653
AGIF: 122856599
CCIN: 107267966
TCA: 655758
DPA: 109539121
SOY: 115885880
ATD: 109598736
CSET: 123314709
AGB: 108910106
LDC: 111504779
NVL: 108562706
APLN: 108740743
PPYR: 116173900
OTU: 111419229
BMOR: 101740691
BMAN: 114244523
MSEX: 115446095
DPL: KGM_207185
BANY: 112048662
PMAC: 106717008
PPOT: 106111764
PXU: 106126099
PRAP: 110999042
ZCE: 119835587
HAW: 110378221
TNL: 113499708
OFU: 114352766
PXY: 105389797
API: 100158737
DNX: 107164769
RMD: 113549417
BTAB: 109030678
DCI: 113470334
CLEC: 106661596
HHAL: 106682080
NLU: 111064340
PHU: Phum_PHUM538550
FOC: 113217977
ZNE: 110836317
CSEC: 111875212
FCD: 110856969
DPX: DAPPUDRAFT_44381
DMK: 116922854
PVM: 113812558
PJA: 122249658
HAME: 121870165
PCLA: 123762829
PTRU: 123501987
HAZT: 108665761
EAF: 111699592
ISC: IscW_ISCW000796
DSV: 119465379
RSAN: 119403156
RMP: 119165283
VDE: 111248677
VJA: 111271616
TUT: 107363777
DPTE: 113789434
DFR: 124497515
PTEP: 107448718
SDM: 118191490
CEL: CELE_ZK1290.2(tph-1)
CBR: CBG_12991(Cbr-tph-1)
LOA: LOAG_01930
NAI: NECAME_08210
HRO: HELRODRAFT_79745
LGI: LOTGIDRAFT_229367
PCAN: 112566861
BGT: 106070864
GAE: 121372139
HRF: 124111829
HRJ: 124255210
CRG: 105336312
MYI: 110454322
PMAX: 117327242
MMER: 123552557
OBI: 106875341
OSN: 115215674
LAK: 106175748
SMM: Smp_174920
OVI: T265_11906
EGL: EGR_07589
APRO: F751_2362
 » show all
Reference
1  [PMID:4402511]
  Authors
Friedman PA, Kappelman AH, Kaufman S.
  Title
Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain.
  Journal
J Biol Chem 247:4165-73 (1972)
Reference
2  [PMID:315449]
  Authors
Hamon M, Bourgoin S, Artaud F, Glowinski J.
  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 33:1031-42 (1979)
DOI:10.1111/j.1471-4159.1979.tb05239.x
Reference
3  [PMID:5309585]
  Authors
Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O.
  Title
Enzymic studies on the biosynthesis of serotonin in mammalian brain.
  Journal
J Biol Chem 245:1699-709 (1970)
Reference
4  [PMID:5789774]
  Authors
Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A.
  Title
Further studies on tryptophan hydroxylase in rat brainstem and beef pineal.
  Journal
Biochem Pharmacol 18:1071-81 (1969)
DOI:10.1016/0006-2952(69)90111-7
Reference
5  [PMID:12379098]
  Authors
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 41:12569-74 (2002)
DOI:10.1021/bi026561f
  Sequence
[hsa:7166]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.16.4
IUBMB Enzyme Nomenclature: 1.14.16.4
ExPASy - ENZYME nomenclature database: 1.14.16.4
BRENDA, the Enzyme Database: 1.14.16.4
CAS: 9037-21-2
LinkDB

DBGET integrated database retrieval system