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
HSA121278(TPH2) 7166(TPH1)
PTR466453(TPH1) 467070(TPH2)
PPS100977344(TPH2) 103782654(TPH1)
GGO101132108(TPH1) 101146582(TPH2)
PON100459809(TPH2) 103891844(TPH1)
NLE100588345(TPH2) 100601780(TPH1)
MCC664730(TPH2) 695363(TPH1)
MCF102124167(TPH2) 102145077(TPH1)
CSAB103238730(TPH2) 103239320(TPH1)
CATY105581034(TPH2) 105598886(TPH1)
PANU101001223(TPH2) 103875499(TPH1)
TGE112606866(TPH1) 112635076(TPH2)
RRO104667637(TPH1) 104668095(TPH2)
RBB108526665(TPH2) 108528377(TPH1)
TFN117081781(TPH1) 117089733(TPH2)
PTEH111552365(TPH2) 111555044(TPH1)
CJC100403096(TPH2) 100415029(TPH1)
SBQ101051709(TPH2) 104652952(TPH1)
CSYR103257543(TPH2) 103265117(TPH1)
MMUR105856884(TPH2) 105879970(TPH1)
OGA100953596(TPH2) 105886446(TPH1)
MMU216343(Tph2) 21990(Tph1)
MCAL110298535(Tph1) 110303601(Tph2)
MPAH110326744(Tph2) 110330199(Tph1)
RNO24848(Tph1) 317675(Tph2)
MCOC116076348(Tph2) 116102248(Tph1)
MUN110550489(Tph1) 110555372(Tph2)
CGE100763947(Tph2) 100767923(Tph1)
PLEU114699018(Tph2) 114700529(Tph1)
NGI103734460(Tph1) 103735331(Tph2)
HGL101710219(Tph1) 101714361(Tph2)
CPOC100718189(Tph1) 100724594(Tph2)
CCAN109679995(Tph1)
DORD105988605(Tph2) 105999169(Tph1)
DSP122117778(Tph1) 122124215(Tph2)
OCU100009100(TPH1) 100101558(TPH1) 100344397(TPH2)
OPI101517264(TPH1) 101524788(TPH2)
TUP102481223(TPH2) 102487889(TPH1)
CFA481165(TPH2) 611956(TPH1)
VVP112922180(TPH2) 112927027(TPH1)
VLG121476514(TPH1) 121491914(TPH2)
AML100467699(TPH1) 100472165(TPH2)
UMR103656892(TPH2) 103679407(TPH1)
UAH113246602(TPH1) 113256261(TPH2)
UAR123787118(TPH2) 123791643(TPH1)
ELK111142174 111150060
MPUF101678853(TPH2) 101685595(TPH1)
ORO101364741(TPH1) 101369839(TPH2)
EJU114202737 114202738 114219387(TPH1)
ZCA113914718(TPH1) 113922464(TPH2) 113933908
MLX118004319(TPH1) 118008557(TPH2)
FCA101082165(TPH2) 101098575(TPH1)
PYU121040737(TPH2) 121043698(TPH1)
PBG122474068(TPH2) 122484410(TPH1)
PTG102948910(TPH2) 102969936(TPH1)
PPAD109270520(TPH2) 109271211(TPH1)
AJU106967384(TPH2) 106977480(TPH1)
HHV120223353(TPH2) 120234792(TPH1)
BTA100336620(TPH2) 781941(TPH1)
BOM102269915(TPH1) 102275621(TPH2)
BIU109558652(TPH2) 109569943(TPH1)
BBUB102396992(TPH2) 102411029(TPH1)
CHX102174722(TPH2) 102184739(TPH1)
OAS101113620(TPH1) 101120314(TPH2)
ODA120857959(TPH2) 120876397(TPH1)
CCAD122427666(TPH2) 122450434(TPH1)
SSC100511002(TPH1) 100627725(TPH2)
CFR102512650(TPH2) 102522464(TPH1)
CBAI105072045(TPH2) 105076585(TPH1)
CDK105086665(TPH1) 105095994(TPH2)
BACU102997866(TPH1) 103006656(TPH2)
LVE103083324(TPH1) 103087968(TPH2)
OOR101271217(TPH2) 101273510(TPH1)
DLE111165253(TPH1) 111173732(TPH2)
PCAD102985446(TPH2) 102994832(TPH1)
PSIU116758349(TPH1) 116761326(TPH2)
ECB100009684(TPH2) 100056614(TPH1)
EPZ103559190(TPH1) 103561950(TPH2)
EAI106826108(TPH2) 106835485(TPH1)
MYB102241626(TPH2) 102244804(TPH1)
MYD102753485(TPH2) 102767513(TPH1)
MMYO118651936(TPH2) 118663522(TPH1)
MLF102418890(TPH1) 102434305(TPH2)
MNA107526733(TPH2) 107546725(TPH1)
PKL118712480(TPH1) 118730418(TPH2)
HAI109387680(TPH2) 109388096(TPH1)
DRO112303363(TPH1) 112319064(TPH2)
SHON118989337(TPH2) 118989705(TPH1)
AJM119053091(TPH1) 119055866
PDIC114499999(TPH1) 114513219(TPH2)
PHAS123810024(TPH1) 123812692(TPH2)
MMF118624020(TPH2) 118628186(TPH1)
RFQ117028733(TPH2) 117030182(TPH1)
PALE102882683(TPH1) 102891331(TPH2)
PGIG120593610(TPH1) 120605080(TPH2)
PVP105301629(TPH2) 105304216(TPH1)
RAY107508027(TPH1) 107512624(TPH2)
MJV108400665(TPH2) 108404860(TPH1)
TOD119248285(TPH2) 119254591(TPH1)
SARA101549071(TPH1) 101551893(TPH2)
LAV100658860(TPH1) 100669911(TPH2)
TMU101355042 101360632
DNM101414982(TPH2) 101440944(TPH1)
MDO100011937(TPH2) 100020009(TPH1)
GAS123250170(TPH2) 123251417(TPH1)
SHR100915442(TPH1) 100923184(TPH2)
PCW110195961(TPH2) 110221097(TPH1)
OAA100079349(TPH2) 100090381(TPH1)
GGA395799(TPH1) 408026(TPH2)
PCOC116226749(TPH2) 116242903(TPH1)
MGP100303678(TPH2) 100549515(TPH1)
CJO107310284(TPH2) 107314681(TPH1)
NMEL110392823(TPH2) 110401279(TPH1)
APLA101793780(TPH2) 101797806(TPH1)
ACYG106042627 106046728(TPH2)
AFUL116490046(TPH1) 116495542(TPH2)
TGU100228542(TPH2) 100229598(TPH1)
LSR110468084(TPH1) 110469834(TPH2)
SCAN103813668(TPH2) 103826774(TPH1)
PMOA120499841(TPH2) 120501148(TPH1)
OTC121339484(TPH2) 121341539(TPH1)
PRUF121352558(TPH2) 121360970(TPH1)
GFR102036017(TPH2) 102041307(TPH1)
FAB101817911(TPH2) 101820220(TPH1)
PHI102103962(TPH2) 102106431(TPH1)
PMAJ107204683(TPH2) 107205260(TPH1)
CCAE111930805(TPH1) 111937577(TPH2)
CCW104685325(TPH1) 104698473(TPH2)
ETL114059440(TPH1) 114059989(TPH2)
ZAB102063944(TPH1) 102067699(TPH2)
FPG101914983(TPH1) 101918183(TPH2)
FCH102052919(TPH2) 102057315(TPH1)
CLV102092014(TPH2) 102095810(TPH1)
EGZ104123206(TPH1) 104132957(TPH2)
NNI104010591(TPH1) 104011038(TPH2)
ACUN113481125(TPH1) 113489370(TPH2)
TALA104356202(TPH1) 104369069(TPH2)
PADL103920030(TPH2) 103920766(TPH1)
ACHC115336364(TPH2) 115352028(TPH1)
AAM106488161(TPH2) 106497047(TPH1)
AROW112964095(TPH2) 112972385(TPH1)
NPD112951457(TPH1) 112958850(TPH2)
DNE112978923(TPH1) 112983291(TPH2)
ASN102376121(TPH2) 102380987(TPH1)
AMJ102560538(TPH1) 102572294(TPH2)
CPOO109315970(TPH2) 109321541(TPH1)
GGN109297011(TPH2) 109299139(TPH1)
PSS102445658(TPH2) 102460535(TPH1)
CMY102930035(TPH2) 102934830(TPH1)
CPIC101933912(TPH2) 101948172(TPH1)
TST117877260(TPH1) 117877915(TPH2)
CABI116817165(TPH2) 116838939(TPH1)
MRV120383209(TPH2) 120402771(TPH1)
ACS100562860(tph1) 100564918(tph2)
PVT110084890(TPH2) 110088804(TPH1)
SUND121929851(TPH1) 121931396(TPH2)
PBI103048564(TPH1) 103062013
PMUR107283841(TPH2) 107296796(TPH1)
TSR106541682(TPH2) 106552357
PGUT117655482(TPH2) 117665266(TPH1)
VKO123021233(TPH1) 123033286(TPH2)
PMUA114598774(TPH1) 114605959(TPH2)
ZVI118089013(TPH1) 118090812(TPH2)
GJA107115340(TPH2) 107115550(TPH1)
XLA108710258 108713144(tph2.S) 387560(tph1.L)
XTR100486097(tph2) 100497239(tph1)
NPR108785999(TPH1) 108788312(TPH2)
RTEM120917010(TPH1) 120931964(TPH2)
BBUF120980604(TPH1) 120980734(TPH2)
BGAR122920144(TPH1) 122925790(TPH2)
DRE352943(tph1a) 407712(tph2) 415103(tph1b)
SRX107720785(tph1) 107740327 107740493 107749937 107750725 107755016
SANH107663941 107670227 107672314 107673292 107686260 107700369
SGH107553080 107557706 107559977 107564603 107569655 107583800
CCAR109074194 109086690 109110720
CAUA113043713 113052380 113066434 113105990 113118311
IPU108259139(tph1b) 108263971(tph2) 108274454(tph1a) 124626828
PHYP113529905(tph1) 113534273 113540934
SMEO124379583(tph1b) 124392964(tph1a) 124395690(tph2)
AMEX103025693 103043966(tph1) 103046451
EEE113582098 113582294 113584487(tph1)
TRU446047(tph1) 446048(tph2)
TNGGSTEN00006938G001
LCO104921438 104932027(tph1) 104938290
NCC104964502(tph1) 104965427
CGOB115004781 115009666(tph1)
ELY117257841 117261799(tph1a) 117261880(tph2)
PLEP121943098 121950084(tph1a)
SLUC116038510(tph1a) 116061876(tph2) 116067391
ECRA117947847 117949802(tph1a)
PFLV114557592 114559910(tph1) 114560174(tph2)
GAT120808697(tph1a) 120809623(tph2) 120833009
PPUG119195577(tph2) 119196279(tph1a) 119229676
MSAM119889771 119893900 119894244(tph2)
CUD121515571(tph2) 121515765(tph1a)
MZE101480764(tph2) 101484460 101486409(tph1)
ONL100691623(tph1) 100694382 100696141
OAU116311354(tph2) 116319109 116326748(tph1a)
OLA101166957(tph2) 101170994 101175562(tph1)
OML112141172 112152292(tph1a) 112161307
XMA102216868(tph1) 102234879 102236889(tph2)
XCO114142506 114150104(tph2) 114151044(tph1)
XHE116710961(tph2) 116718124 116729036(tph1)
PRET103462259 103466377(tph2) 103466482(tph1)
PFOR103130852 103149204 103156520(tph1)
PLAI106942220 106947747(tph1) 106959120
PMEI106905963(tph2) 106925763 106933112(tph1)
GAF122835380(tph1a) 122836199(tph2) 122846231
CVG107099807(tph2) 107101475 107103791(tph1)
CTUL119773716 119781658(tph2) 119787407(tph1a)
NFU107381938 107388661(tph1) 107389098(tph2)
KMR108229864(tph1a) 108237877 108251439(tph2)
ALIM106516735 106521168(tph1) 106531022(tph2)
NWH119415797(tph1a) 119416121(tph2) 119423870
AOCE111578292 111584097(tph1)
CSEM103379608(tph2) 103380212(tph1)
POV109624178(tph1) 109644721
SSEN122775398(tph2) 122776545(tph1a)
HHIP117762606(tph1a) 117762648(tph2)
LCF108876698(tph1) 108891738(tph2)
SDU111229584(tph1) 111233710(tph2)
SLAL111648930 111667055(tph1)
XGL120793262(tph2) 120793556(tph1a)
HCQ109507516(tph1) 109518199(tph2) 109529786
BPEC110162577 110168313(tph2) 110169358(tph1)
MALB109951036(tph1) 109969076(tph2)
SASA106561539 106562311 106584760 106587468
OTW112218837(tph2) 112236633 112237058(tph1a) 112249279
OMY110499357(tph2) 110506638 110521183(tph1a) 110526507
OGO124033100 124033744(tph2) 124035648 124037467(tph1a)
ONE115111128 115113690 115126650 115133981
SALP111962707 111969461 111974702 112073037
SNH120025196 120051724(tph1a) 120056450 120066714(tph2)
ELS105018201(tph1) 105018238(tph2)
SFM108936426(tph2) 108941264 108942210
PKI111834510 111835440 111851447(tph2)
AANG118214860 118219170(tph2) 118227486
LOC102682173(tph2) 102697783(tph1)
PSPA121294421 121318037 121320056 121330423(tph1a)
ARUT117415915 117419550 117432389 117434745(tph1a)
LCM102362567(TPH1) 102363250(TPH2)
CMK103174831 103185330
RTP109927655 109935866
BFO118406289 118406966
BBEL109480215
CIN100049066
SCLV120335756
SPU115922565 578903
APLC110981081
SKO100329006(tph-1)
DMEDmel_CG9122(Trh)
DER6543860
DSE6610268
DSIDsimw501_GD13494(Dsim_GD13494)
DYADyak_GE20982
DAN6492953
DSR110178615
DPODpse_GA21560
DPE6603951
DMN108153552
DWI6639428
DGR6558602
DMODmoj_GI12709
DAZ108614428
DNV108651306
DHE111600458
DVI6623307
CCAT101460734
BOD106622704
MDE101893101
SCAC106092589
LCQ111676820
AGAAgaP_AGAP006020
ACOZ120952581
AARA120896557
AAG23687540
AALB109413958
CQUCpipJ_CPIJ019741
CPII120412891
CNS116345266
AME411200
ACER108003440
ALAB122716618
BIM100742465
BBIF117204398
BVK117233459
BVAN117153441
BTER100647460
BPYO122569193
CCAL108624633
OBB114876888
MGEN117223613
NMEA116424137
CGIG122395229
SOC105194454
MPHA105839937
AEC105145053
ACEP105619346
PBAR105430282
VEM105567116
HST105182103
DQU106750935
CFO105251016
FEX115233862
LHU105678051
PGC109861523
OBO105279028
PCF106791737
PFUC122524389
VPS122634219
NVI100123183
CSOL105363200
TPRE106653657
MDL103579283
CGLO123267565
FAS105264297
DAM107046653
AGIF122856599
CCIN107267966
TCA655758
DPA109539121
SOY115885880
ATD109598736
CSET123314709
AGB108910106
LDC111504779
NVL108562706
APLN108740743
PPYR116173900
OTU111419229
BMOR101740691
BMAN114244523
MSEX115446095
DPLKGM_207185
BANY112048662
PMAC106717008
PPOT106111764
PXU106126099
PRAP110999042
ZCE119835587
HAW110378221
TNL113499708
OFU114352766
PXY105389797
API100158737
DNX107164769
RMD113549417
BTAB109030678
DCI113470334
CLEC106661596
HHAL106682080
NLU111064340
PHUPhum_PHUM538550
FOC113217977
ZNE110836317
CSEC111875212
FCD110856969
DPXDAPPUDRAFT_44381
DMK116922854
PVM113812558
PJA122249658
HAME121870165
PCLA123762829
PTRU123501987
HAZT108665761
EAF111699592
ISCIscW_ISCW000796
DSV119465379
RSAN119403156
RMP119165283
VDE111248677
VJA111271616
TUT107363777
DPTE113789434
DFR124497515
PTEP107448718
SDM118191490
CELCELE_ZK1290.2(tph-1)
CBRCBG_12991(Cbr-tph-1)
LOALOAG_01930
NAINECAME_08210
HROHELRODRAFT_79745
LGILOTGIDRAFT_229367
PCAN112566861
BGT106070864
GAE121372139
HRF124111829
HRJ124255210
CRG105336312
MYI110454322
PMAX117327242
MMER123552557
OBI106875341
OSN115215674
LAK106175748
SMMSmp_174920
OVIT265_11906
EGLEGR_07589
APROF751_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
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