KEGG   ENZYME: 1.14.16.1Help
Entry
EC 1.14.16.1                Enzyme                                 
Name
phenylalanine 4-monooxygenase;
phenylalaninase;
phenylalanine 4-hydroxylase;
phenylalanine hydroxylase
Class
Oxidoreductases;
Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2;
With reduced pteridine as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)
Reaction(IUBMB)
L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin [RN:R07211]
Reaction(KEGG)
R07211;
(other) R01795
Show
Substrate
L-phenylalanine [CPD:C00079];
tetrahydrobiopterin [CPD:C00272];
O2 [CPD:C00007]
Product
L-tyrosine [CPD:C00082];
4a-hydroxytetrahydrobiopterin [CPD:C15522]
Comment
The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, 6,7-dihydropteridine reductase, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
Pathway
Phenylalanine metabolism
Phenylalanine, tyrosine and tryptophan biosynthesis
Metabolic pathways
Orthology
K00500  
phenylalanine-4-hydroxylase
Genes
HSA: 
5053(PAH)
PTR: 
741097(PAH)
PPS: 
GGO: 
PON: 
MCC: 
698696(PAH)
MMU: 
18478(Pah)
RNO: 
24616(Pah)
CFA: 
475446(PAH)
AML: 
FCA: 
101081741(PAH)
BTA: 
510583(PAH)
SSC: 
100521900
ECB: 
100053361(PAH)
MDO: 
100021400(PAH)
SHR: 
100919346(PAH)
OAA: 
100076018
GGA: 
408024(PAH)
MGP: 
100543812
TGU: 
100229122(PAH)
ACS: 
100562752
XTR: 
613076(pah)
DRE: 
378962(pah)
TRU: 
446049(pah)
OLA: 
101163702
BFO: 
BRAFLDRAFT_115951
CIN: 
100181935
SPU: 
581035
DME: 
Dmel_CG7399(Hn)
DPO: 
Dpse_GA20325
DAN: 
Dana_GF10325
DER: 
Dere_GG14450
DPE: 
Dper_GL18039
DSE: 
Dsec_GM25002
DSI: 
Dsim_GD14035
DWI: 
Dwil_GK21215
DYA: 
Dyak_GE21640(Dyak_Hn)
DGR: 
Dgri_GH14976
DMO: 
Dmoj_GI13137
DVI: 
Dvir_GJ13886
AGA: 
AgaP_AGAP005712
CQU: 
CpipJ_CPIJ002148
AME: 
408622
NVI: 
100115984(NV18416)
TCA: 
655392
API: 
100166971
PHU: 
Phum_PHUM426310
CBR: 
CBG03166(Cbr-pah-1)
TSP: 
Tsp_08577
NVE: 
NEMVE_v1g237576
HMG: 
100197101
TAD: 
TRIADDRAFT_32954
AQU: 
100631768
VCN: 
VOLCADRAFT_96350
CME: 
CMJ066C
MBR: 
MONBRDRAFT_31770
NGR: 
NAEGRDRAFT_77920 NAEGRDRAFT_83269
DDI: 
DDB_G0278781(pah)
DPP: 
DICPUDRAFT_48007
TGO: 
TGME49_012740
TET: 
TTHERM_00829460
PTM: 
GSPATT00004497001 GSPATT00031660001
LMA: 
LMJF_28_1280(PAH)
LIF: 
LINJ_28_1390(PAH)
LDO: 
LDBPK_281390
LMI: 
LMXM_28_1280
LBZ: 
LBRM_28_1380(PAH)
PTI: 
PHATRDRAFT_13175
TPS: 
THAPSDRAFT_bd415(PAH1)
PIF: 
PITG_02210
XCC: 
XCC0156(phhA)
XCB: 
XC_0165(phhA)
XCA: 
xccb100_0173(phhA)
XCV: 
XCV0157(phhA)
XCP: 
XCR_4381(phhA)
XAC: 
XAC0174(phhA)
XAX: 
XACM_0158(phhA)
XAO: 
XAC29_00890(phhA)
XOO: 
XOO0267(phhA)
XOM: 
XOO_0243(phhA)
XOP: 
PXO_03285(phhA)
XOR: 
XOC_0260(phhA)
XAL: 
XALc_0054(phhA)
XCI: 
XCAW_00569(phhA)
SML: 
Smlt0077(phhA)
SMT: 
Smal_0032(phhA)
BUJ: 
BurJV3_0031
SMZ: 
SMD_0029(phhA)
PSU: 
Psesu_0042
PSD: 
DSC_01655(phhA)
RHD: 
R2APBS1_0035
VCH: 
VCA0828(phhA)
VCE: 
Vch1786_II0518(phhA)
VCJ: 
VCD_000497(phhA)
VCO: 
VC0395_0407(phhA)
VCR: 
VC395_A0852(phhA)
VCM: 
VCM66_A0787(phhA)
VCI: 
O3Y_17393(phhA)
VCL: 
VCLMA_B0604
VVU: 
VV2_0455(phhA)
VVY: 
VVA1005(phhA)
VVM: 
VVMO6_03925
VPA: 
VPA0576(phhA)
VPB: 
VPBB_A0526
VHA: 
VIBHAR_05421(phhA)
VSP: 
VS_II1509(phhA)
VEX: 
VEA_001480
VEJ: 
VEJY3_21801(phhA)
VFU: 
vfu_B00650
PPR: 
PBPRB1164(phhA)
VAN: 
VAA_02977
PAE: 
PA0872(phhA)
PAU: 
PA14_52990(phhA)
PAP: 
PSPA7_4644(phhA)
PAG: 
PLES_44441(phhA)
PAF: 
PAM18_4167(phhA)
PNC: 
NCGM2_1648(phhA)
PDK: 
PADK2_21340(phhA)
PPU: 
PP_4490(phhA)
PPF: 
Pput_1424(phhA)
PPG: 
PputGB1_3995(phhA)
PPW: 
PputW619_3779(phhA)
PPT: 
PPS_3835
PPB: 
PPUBIRD1_1411(phhA)
PPI: 
YSA_07921
PPX: 
T1E_4057(phhA)
PPUH: 
B479_19060(phhA)
PPUU: 
PputUW4_03913(phhA)
PST: 
PSPTO_1822(phhA)
PSB: 
Psyr_3575(phhA)
PSP: 
PSPPH_3531(phhA)
PFL: 
PFL_1611(phhA)
PFO: 
Pfl01_1499(phhA)
PFS: 
PFLU4458(phhA)
PFE: 
PSF113_1529(phhA)
PFC: 
PflA506_3764(phhA)
PPZ: 
H045_13220(phhA)
PEN: 
PSEEN3892(phhA)
PMY: 
Pmen_3112(phhA)
PMK: 
MDS_3411
PSA: 
PST_3562(phhA)
PSZ: 
PSTAB_3534(phhA)
PSR: 
PSTAA_3659(phhA)
PSC: 
A458_03640(phhA)
PSJ: 
PSJM300_16230(phhA)
PSH: 
Psest_0781
PBA: 
PSEBR_a1450
PFV: 
Psefu_2666
PDR: 
H681_17035(phhA)
AVN: 
Avin_34650(phhA)
PCR: 
Pcryo_1554(phhA)
PRW: 
PsycPRwf_1041(phhA)
SON: 
SO_1666(phhA)
SDN: 
Sden_2595(phhA)
SFR: 
Sfri_1328(phhA)
SAZ: 
Sama_2222(phhA)
SBL: 
Sbal_1484(phhA)
SBM: 
Shew185_1479(phhA)
SBN: 
Sbal195_1515(phhA)
SBP: 
Sbal223_2868(phhA)
SBT: 
Sbal678_1551
SBS: 
Sbal117_1593
SBB: 
Sbal175_2849
SLO: 
Shew_1435(phhA)
SPC: 
Sputcn32_1386(phhA)
SHP: 
Sput200_1401
SSE: 
Ssed_2930(phhA)
SPL: 
Spea_1448(phhA)
SHE: 
Shewmr4_2607(phhA)
SHM: 
Shewmr7_2674(phhA)
SHN: 
Shewana3_2781(phhA)
SHW: 
Sputw3181_2715(phhA)
SHL: 
Shal_1531(phhA)
SWD: 
Swoo_1715(phhA)
SWP: 
swp_1650(phhA)
SVO: 
SVI_1532(phhA)
ILO: 
IL0725(phhA)
CPS: 
CPS_3766(phhA)
PHA: 
PSHAa2043(phhA)
PAT: 
Patl_2999(phhA)
PSM: 
PSM_A2107(phhA)
AMC: 
MADE_1006175(phhA)
AMAC: 
MASE_05135(phhA)
AMB: 
AMBAS45_05365(phhA)
AMG: 
AMEC673_05220(phhA)
AMK: 
AMBLS11_05245(phhA)
AMAA: 
amad1_05550(phhA)
ALT: 
ambt_13010(phhA)
GAG: 
Glaag_1329
GNI: 
GNIT_2313(phhA)
GPS: 
C427_3616(phhA)
FBL: 
Fbal_2580
LPN: 
lpg2647(phhA)
LPU: 
LPE509_00385
LPF: 
lpl2572(phhA)
LPP: 
lpp2700(phhA)
LPC: 
LPC_0492(phhA)
LPA: 
lpa_03875
LPE: 
lp12_2640
LLO: 
LLO_2654(phhA)
HCH: 
HCH_00956(phhA)
HEL: 
HELO_2254(phhA)
KKO: 
Kkor_1221(phhA) Kkor_1520(phhA)
AHA: 
AHA_1883(phhA)
ASA: 
ASA_2420(phhA)
AVR: 
B565_1620
OCE: 
GU3_14495(phhA)
SAGA: 
M5M_12230
CVI: 
CV_3180(phhA)
PSE: 
NH8B_0637
RSO: 
RSc3355(phhA)
RSC: 
RCFBP_10110(phhA)
RSL: 
RPSI07_0089(phhA)
RSN: 
RSPO_c00086(phhA)
RPI: 
Rpic_3549(phhA)
RPF: 
Rpic12D_3225(phhA)
REU: 
Reut_A3387(phhA)
REH: 
H16_A3678(phhA)
RME: 
Rmet_3533(phhA)
CTI: 
RALTA_A3134(phhA)
CNC: 
CNE_1c36300(phhA)
BMA: 
BMA2927(phhA)
BMV: 
BMASAVP1_A3383(phhA)
BML: 
BMA10229_A1616(phhA)
BMN: 
BMA10247_2986(phhA)
BPS: 
BPSL3424(phhA)
BPM: 
BURPS1710b_0206(phhA)
BPL: 
BURPS1106A_4075(phhA)
BPD: 
BURPS668_4001(phhA)
BPR: 
GBP346_A4179(phhA)
BPZ: 
BP1026B_I3716(phhA)
BPQ: 
BPC006_I4108
BTE: 
BTH_I3337(phhA)
BVI: 
Bcep1808_0088(phhA)
BUR: 
Bcep18194_A3259(phhA)
BCN: 
Bcen_2977(phhA)
BCH: 
Bcen2424_0078(phhA)
BCM: 
Bcenmc03_0096(phhA)
BCJ: 
BCAL0010(phhA)
BAM: 
Bamb_0069(phhA)
BAC: 
BamMC406_0077(phhA)
BMU: 
Bmul_0078(phhA)
BMJ: 
BMULJ_03187(phhA)
BCT: 
GEM_0073
BXE: 
Bxe_A0011(phhA)
BPY: 
Bphyt_3921(phhA)
BGL: 
bglu_1g00530
BGE: 
BC1002_3128
BGD: 
bgla_1g00640
BUK: 
MYA_0073
AKA: 
TKWG_18190(phhA)
POL: 
Bpro_0168(phhA) Bpro_4215(phhA)
PNA: 
Pnap_1117(phhA)
AAV: 
Aave_4193(phhA)
AJS: 
Ajs_0518(phhA)
DIA: 
Dtpsy_0534(phhA)
AAA: 
Acav_4063
ACK: 
C380_02955(phhA)
VEI: 
Veis_2136(phhA)
DAC: 
Daci_1267(phhA)
DEL: 
DelCs14_5250
VAP: 
Vapar_4768(phhA)
VPE: 
Varpa_5425
CTT: 
CtCNB1_4248
ADN: 
Alide_0627
ADK: 
Alide2_0592
RTA: 
Rta_05490(phhA)
MPT: 
Mpe_A0347(phhA)
HSE: 
Hsero_4280(phhA)
CFU: 
CFU_4019(pah)
LCH: 
Lcho_2046(phhA)
TIN: 
Tint_1003
THI: 
THI_1261(phhA)
RGE: 
RGE_43970(phhA)
BBA: 
Bd3537(phhA)
BBAT: 
Bdt_3444(phhA)
BEX: 
A11Q_2247
ADE: 
Adeh_2800(phhA)
ACP: 
A2cp1_2986
AFW: 
Anae109_2753
ANK: 
AnaeK_2895
MXA: 
MXAN_5127(phhA)
MFU: 
LILAB_33600
MSD: 
MYSTI_05617
CCX: 
COCOR_04907(phhA)
SUR: 
STAUR_1300
SCL: 
sce5266(phhA)
RBE: 
RBE_1408(phhA)
RBO: 
A1I_07840(phhA)
MLO: 
mlr4831(phhA)
MCI: 
Mesci_0618
MOP: 
Mesop_0628
MAM: 
Mesau_00447
ARA: 
Arad_8207(phhA)
RET: 
RHE_CH01742(phhA)
REC: 
RHECIAT_CH0001823(phhA)
RLE: 
RL1860(phhA)
RLT: 
Rleg2_1403(phhA)
RLG: 
Rleg_1507(phhA)
MSC: 
BN69_0991
CCR: 
CC_1612(phhA)
CCS: 
CCNA_01684(phhA)
CAK: 
Caul_2208(phhA)
CSE: 
Cseg_2596
PZU: 
PHZ_c1409(phhA)
BSB: 
Bresu_1338
AEX: 
Astex_0687
MMR: 
Mmar10_1853(phhA)
HNE: 
HNE_1395(phhA)
HBA: 
Hbal_2665(phhA)
NAR: 
Saro_3187(phhA)
NPP: 
PP1Y_AT6800
SAL: 
Sala_0553(phhA) Sala_1392(phhA)
SPHM: 
G432_16830(phhA)
SJP: 
SJA_C2-00380
SCH: 
Sphch_3216
SSY: 
SLG_11900(phhA)
ELI: 
ELI_12050(phhA)
RCE: 
RC1_3346(phhA)
TMO: 
TMO_0657(phhA)
MAI: 
MICA_271(phhA)
MAN: 
A11S_269
BAN: 
BA_4586(phhA)
BAR: 
GBAA_4586(phhA)
BAT: 
BAS4253(phhA)
BAH: 
BAMEG_4622
BAI: 
BAA_4605
BAX: 
H9401_4374
BAL: 
BACI_c43440(pah)
BCE: 
BC4352(phhA)
BCA: 
BCE_4439
BCZ: 
BCZK4102(phhA)
BCR: 
BCAH187_A4489
BCB: 
BCB4264_A4477
BCU: 
BCAH820_4438
BCG: 
BCG9842_B0759
BCQ: 
BCQ_4142(pah)
BCX: 
BCA_4470
BNC: 
BCN_4268
BCF: 
bcf_21675
BCER: 
BCK_13410
BCY: 
Bcer98_3076
BTK: 
BT9727_4091(phhA)
BTL: 
BALH_3943(phhA)
BTB: 
BMB171_C4020
BTT: 
HD73_4665
BTC: 
CT43_CH4374
BTF: 
YBT020_21460
BTM: 
MC28_3648
BTG: 
BTB_c44980
BTI: 
BTG_27295
BTN: 
BTF1_20395
BTHT: 
H175_ch4444
BWE: 
BcerKBAB4_4205
ESI: 
Exig_1060
EAT: 
EAT1b_2009
EAN: 
Eab7_1032
NFA: 
nfa9410(phhA)
NCY: 
NOCYR_1007(phhA)
NBR: 
O3I_005335(phhA)
BCV: 
Bcav_3578(phhA)
CFI: 
Celf_2069
MPH: 
MLP_36500
TCU: 
Tcur_3717
SRO: 
Sros_8337
FRE: 
Franean1_5444(phhA)
TBI: 
Tbis_1027
SESP: 
BN6_28610
ABA: 
Acid345_1076(phhA)
ACA: 
ACP_3318(phhA)
ACM: 
AciX9_2100
GMA: 
AciX8_2764
SUS: 
Acid_4098(phhA)
CTM: 
Cabther_A0770
SRU: 
SRU_2069(phhA)
SRM: 
SRM_02286(phhA)
PHE: 
Phep_3273
SCN: 
Solca_0389
SGN: 
SGRA_1091(phhA)
CMR: 
Cycma_3117
BBD: 
Belba_3403
EVI: 
Echvi_2513
CHU: 
CHU_3025(phhA)
DFE: 
Dfer_2108
SLI: 
Slin_6319
LBY: 
Lbys_0242
RSI: 
Runsl_5125
FLI: 
Fleli_2781
EOL: 
Emtol_3645
FAE: 
FAES_1109
MTT: 
Ftrac_1424
GFO: 
GFO_0233(phhA)
FJO: 
Fjoh_1902(phhA)
FPS: 
FP1954(phhA)
FCO: 
FCOL_10665
FIN: 
KQS_10995(phhA)
RBI: 
RB2501_09225
ZPR: 
ZPR_0791
CAT: 
CA2559_05350
FBC: 
FB2170_08864
CAO: 
Celal_0799
CLY: 
Celly_0690
WVI: 
Weevi_1706
KDI: 
Krodi_1612
LAN: 
Lacal_1606
ZGA: 
zobellia_969(phhA)
MRS: 
Murru_0808
ASL: 
Aeqsu_1773
PTQ: 
P700755_001078
NDO: 
DDD_0620(phhA)
POM: 
MED152_07605
IAL: 
IALB_1335(phhA)
CAU: 
Caur_2799
CAG: 
Cagg_0605
CHL: 
Chy400_3030
HAU: 
Haur_3847
 » show all
Taxonomy
Reference
1  [PMID:5773277]
  Authors
Guroff G, Rhoads CA.
  Title
Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a). Nature of the cofactor.
  Journal
J. Biol. Chem. 244 (1969) 142-6.
  Organism
Pseudomonas sp.
Reference
2  [PMID:14404870]
  Authors
KAUFMAN S.
  Title
Studies on the mechanism of the enzymatic conversion of phenylalanine to tyrosine.
  Journal
J. Biol. Chem. 234 (1959) 2677-82.
  Organism
Rattus norvegicus [GN:rno], Ovis aries
Reference
3  [PMID:13292928]
  Authors
MITOMA C.
  Title
Studies on partially purified phenylalanine hydroxylase.
  Journal
Arch. Biochem. Biophys. 60 (1956) 476-84.
  Organism
Rattus norvegicus [GN:rno]
Reference
4  [PMID:14927641]
  Authors
UDENFRIEND S, COOPER JR.
  Title
The enzymatic conversion of phenylalanine to tyrosine.
  Journal
J. Biol. Chem. 194 (1952) 503-11.
  Organism
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno], Canis familiaris [GN:cfa], Gallus gallus [GN:gga], Cavia porcellus, Oryctolagus cuniculus
Reference
5  [PMID:7779797]
  Authors
Carr RT, Balasubramanian S, Hawkins PC, Benkovic SJ.
  Title
Mechanism of metal-independent hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase.
  Journal
Biochemistry. 34 (1995) 7525-32.
  Organism
Chromobacterium violaceum [GN:cvi]
Reference
6  [PMID:11718561]
  Authors
Andersen OA, Flatmark T, Hough E.
  Title
High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin.
  Journal
J. Mol. Biol. 314 (2001) 279-91.
  Organism
Homo sapiens [GN:hsa]
Reference
7  [PMID:12096915]
  Authors
Erlandsen H, Kim JY, Patch MG, Han A, Volner A, Abu-Omar MM, Stevens RC.
  Title
Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates.
  Journal
J. Mol. Biol. 320 (2002) 645-61.
  Organism
Homo sapiens [GN:hsa]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
9029-73-6
DBGET integrated database retrieval system