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 incorporation or reduction of molecular oxygen;
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.
History
EC 1.14.16.1 created 1961 as EC 1.99.1.2, transferred 1965 to EC 1.14.3.1, transferred 1972 to EC 1.14.16.1, modified 2002, modified 2003
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)
MCF: 
MMU: 
18478(Pah)
RNO: 
24616(Pah)
CGE: 
HGL: 
TUP: 
CFA: 
475446(PAH)
AML: 
FCA: 
BTA: 
510583(PAH)
BOM: 
PHD: 
CHX: 
SSC: 
CFR: 
ECB: 
MYB: 
MDO: 
SHR: 
OAA: 
GGA: 
408024(PAH)
MGP: 
TGU: 
FAB: 
PHI: 
APLA: 
FPG: 
FCH: 
CLV: 
ASN: 
PSS: 
ACS: 
XTR: 
613076(pah)
DRE: 
378962(pah)
TRU: 
446049(pah)
MZE: 
OLA: 
XMA: 
LCM: 
BFO: 
CIN: 
SPU: 
DME: 
DPO: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
Dyak_GE21640(Dyak_Hn)
DGR: 
DMO: 
DVI: 
AGA: 
CQU: 
AME: 
408622(GB18494)
NVI: 
TCA: 
BMOR: 
API: 
PHU: 
CBR: 
CBG03166(Cbr-pah-1)
TSP: 
NVE: 
HMG: 
TAD: 
AQU: 
VCN: 
CME: 
GSL: 
MBR: 
DDI: 
DPP: 
DFA: 
ACAN: 
TGO: 
TET: 
PTM: 
PTI: 
TPS: 
PIF: 
NGD: 
GTT: 
LMA: 
LIF: 
LDO: 
LMI: 
LBZ: 
NGR: 
XCC: 
XCC0156(phhA)
XCB: 
XC_0165(phhA)
XCA: 
XCV: 
XCV0157(phhA)
XCP: 
XCR_4381(phhA)
XAC: 
XAC0174(phhA)
XAX: 
XACM_0158(phhA)
XAO: 
XOO: 
XOO0267(phhA)
XOM: 
XOO_0243(phhA)
XOP: 
PXO_03285(phhA)
XOR: 
XOC_0260(phhA)
XAL: 
XALc_0054(phhA)
XCI: 
SML: 
Smlt0077(phhA)
SMT: 
Smal_0032(phhA)
BUJ: 
SMZ: 
SMD_0029(phhA)
PSU: 
PSD: 
DSC_01655(phhA)
RHD: 
VCH: 
VCA0828(phhA)
VCE: 
VCJ: 
VCO: 
VCR: 
VCM: 
VCI: 
O3Y_17393(phhA)
VCL: 
VVU: 
VV2_0455(phhA)
VVY: 
VVA1005(phhA)
VVM: 
VPA: 
VPA0576(phhA)
VPB: 
VPK: 
VPF: 
VHA: 
VCA: 
VAG: 
VSP: 
VS_II1509(phhA)
VEX: 
VEJ: 
VFU: 
VNI: 
PPR: 
PBPRB1164(phhA)
VAN: 
LAG: 
PAE: 
PA0872(phhA)
PAU: 
PAP: 
PAG: 
PAF: 
PNC: 
PDK: 
PSG: 
PRP: 
PAEP: 
PAER: 
PAEM: 
PAEL: 
PAES: 
PPU: 
PP_4490(phhA)
PPF: 
Pput_1424(phhA)
PPG: 
PPW: 
PPT: 
PPB: 
PPI: 
PPX: 
T1E_4057(phhA)
PPUH: 
PPUT: 
PPUN: 
PP4_13300(phhA)
PPUU: 
PST: 
PSB: 
Psyr_3575(phhA)
PSP: 
PCI: 
PFL: 
PFL_1611(phhA)
PPRC: 
PFO: 
PFS: 
PFLU4458(phhA)
PFE: 
PFC: 
PPZ: 
PEN: 
PSEEN3892(phhA)
PMY: 
Pmen_3112(phhA)
PMK: 
PSA: 
PST_3562(phhA)
PSZ: 
PSR: 
PSC: 
PSJ: 
PSH: 
PBA: 
PFV: 
PDR: 
PRE: 
PSV: 
PSK: 
PMON: 
PMOT: 
AVN: 
AVL: 
AVD: 
PCR: 
PRW: 
PSO: 
SON: 
SO_1666(phhA)
SDN: 
Sden_2595(phhA)
SFR: 
Sfri_1328(phhA)
SAZ: 
Sama_2222(phhA)
SBL: 
Sbal_1484(phhA)
SBM: 
SBN: 
SBP: 
SBT: 
SBS: 
SBB: 
SLO: 
Shew_1435(phhA)
SPC: 
SHP: 
SSE: 
Ssed_2930(phhA)
SPL: 
Spea_1448(phhA)
SHE: 
SHM: 
SHN: 
SHW: 
SHL: 
Shal_1531(phhA)
SWD: 
Swoo_1715(phhA)
SWP: 
swp_1650(phhA)
SVO: 
SVI_1532(phhA)
ILO: 
IL0725(phhA)
ILI: 
CPS: 
CPS_3766(phhA)
PHA: 
PSHAa2043(phhA)
PAT: 
Patl_2999(phhA)
PSM: 
PSM_A2107(phhA)
AMC: 
AMAC: 
AMB: 
AMG: 
AMH: 
AMK: 
AMAA: 
AMAL: 
AMAE: 
AMAO: 
AMAD: 
AMAI: 
ALT: 
GAG: 
GNI: 
GNIT_2313(phhA)
GPS: 
C427_3616(phhA)
FBL: 
LPN: 
lpg2647(phhA)
LPU: 
LPH: 
LPV_2990(phhA)
LPO: 
LPO_2925(phhA)
LPM: 
LP6_2678(phhA)
LPF: 
lpl2572(phhA)
LPP: 
lpp2700(phhA)
LPC: 
LPC_0492(phhA)
LPA: 
LPE: 
LLO: 
LLO_2654(phhA)
HCH: 
HCH_00956(phhA)
HEL: 
HELO_2254(phhA)
KKO: 
Kkor_1221(phhA) Kkor_1520(phhA)
AHA: 
AHA_1883(phhA)
AHY: 
ASA: 
ASA_2420(phhA)
AVR: 
OCE: 
GU3_14495(phhA)
SAGA: 
CVI: 
CV_3180(phhA)
PSE: 
RSO: 
RSc3355(phhA)
RSC: 
RSL: 
RSN: 
RSM: 
RSE: 
RPI: 
Rpic_3549(phhA)
RPF: 
REU: 
REH: 
H16_A3678(phhA)
RME: 
Rmet_3533(phhA)
CTI: 
CNC: 
BMA: 
BMA2927(phhA)
BMV: 
BML: 
BMN: 
BPS: 
BPSL3424(phhA)
BPM: 
BPL: 
BPD: 
BPR: 
BPSE: 
BDL_1953(phhA)
BPZ: 
BPQ: 
BPK: 
BBK_1440(phhA)
BTE: 
BTH_I3337(phhA)
BTD: 
BTI_135(phhA)
BVI: 
BUR: 
BCN: 
Bcen_2977(phhA)
BCH: 
BCM: 
BCJ: 
BCAL0010(phhA)
BAM: 
Bamb_0069(phhA)
BAC: 
BMU: 
Bmul_0078(phhA)
BMJ: 
BCT: 
BXE: 
Bxe_A0011(phhA)
BPY: 
BGL: 
BGE: 
BGD: 
BUK: 
PPK: 
PRB: 
AKA: 
POL: 
Bpro_0168(phhA) Bpro_4215(phhA)
PNA: 
Pnap_1117(phhA)
AAV: 
Aave_4193(phhA)
AJS: 
Ajs_0518(phhA)
DIA: 
AAA: 
ACK: 
VEI: 
Veis_2136(phhA)
DAC: 
Daci_1267(phhA)
DEL: 
VAP: 
VPE: 
VPD: 
CTT: 
ADN: 
ADK: 
RTA: 
Rta_05490(phhA)
MPT: 
Mpe_A0347(phhA)
HSE: 
CFU: 
LCH: 
Lcho_2046(phhA)
TIN: 
THI: 
THI_1261(phhA)
RGE: 
RGE_43970(phhA)
BBA: 
Bd3537(phhA)
BBAT: 
Bdt_3444(phhA)
BEX: 
ADE: 
Adeh_2800(phhA)
ACP: 
AFW: 
ANK: 
MXA: 
MXAN_5127(phhA)
MFU: 
MSD: 
CCX: 
SUR: 
SCL: 
sce5266(phhA)
RBE: 
RBE_1408(phhA)
RBO: 
A1I_07840(phhA)
MLO: 
mlr4831(phhA)
MCI: 
MOP: 
MAM: 
ARA: 
Arad_8207(phhA)
RET: 
REC: 
REL: 
RLE: 
RL1860(phhA)
RLT: 
RLG: 
Rleg_1507(phhA)
MSC: 
CCR: 
CC_1612(phhA)
CCS: 
CAK: 
Caul_2208(phhA)
CSE: 
PZU: 
PHZ_c1409(phhA)
BSB: 
AEX: 
MMR: 
HNE: 
HNE_1395(phhA)
HBA: 
Hbal_2665(phhA)
NAR: 
Saro_3187(phhA)
NPP: 
SAL: 
Sala_0553(phhA) Sala_1392(phhA)
SPHM: 
SJP: 
SCH: 
SSY: 
SLG_11900(phhA)
ELI: 
ELI_12050(phhA)
RCE: 
RC1_3346(phhA)
TMO: 
TMO_0657(phhA)
MAI: 
MICA_271(phhA)
MAN: 
BAN: 
BA_4586(phhA)
BAR: 
GBAA_4586(phhA)
BAT: 
BAS4253(phhA)
BAH: 
BAI: 
BAX: 
BANT: 
BANR: 
BAL: 
BCE: 
BC4352(phhA)
BCA: 
BCZ: 
BCZK4102(phhA)
BCR: 
BCB: 
BCU: 
BCG: 
BCQ: 
BCX: 
BNC: 
BCF: 
BCER: 
BCY: 
BTK: 
BTL: 
BALH_3943(phhA)
BTB: 
BTT: 
BTC: 
BTF: 
BTM: 
BTG: 
BTI: 
BTN: 
BTHT: 
BTHU: 
BWE: 
BTY: 
ESI: 
EAT: 
EAN: 
EXM: 
NFA: 
nfa9410(phhA)
NCY: 
NBR: 
BCV: 
Bcav_3578(phhA)
CFI: 
MPH: 
TCU: 
SRO: 
FRE: 
TBI: 
SESP: 
ABA: 
ACA: 
ACP_3318(phhA)
ACM: 
GMA: 
SUS: 
Acid_4098(phhA)
CTM: 
GLJ: 
GKIL_3071(phhA)
SRU: 
SRU_2069(phhA)
SRM: 
SRM_02286(phhA)
PHE: 
SCN: 
SGN: 
SGRA_1091(phhA)
CMR: 
BBD: 
EVI: 
CHU: 
CHU_3025(phhA)
DFE: 
SLI: 
LBY: 
RSI: 
FLI: 
EOL: 
FAE: 
MTT: 
GFO: 
GFO_0233(phhA)
FJO: 
Fjoh_1902(phhA)
FPS: 
FP1954(phhA)
FCO: 
FIN: 
KQS_10995(phhA)
RBI: 
ZPR: 
CAT: 
FBC: 
CAO: 
CLY: 
WVI: 
KDI: 
LAN: 
ZGA: 
MRS: 
ASL: 
PTQ: 
NDO: 
DDD_0620(phhA)
POM: 
IAL: 
IALB_1335(phhA)
CAU: 
CAG: 
CHL: 
HAU: 
CCZ: 
 » 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]
  Sequence
[hsa:5053]
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], Chromobacterium violaceum [GN:cvi]
  Sequence
[cvi:CV_3180]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
9029-73-6

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