| Entry |
|
|---|
| 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
 |
|---|
| 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
 |
|---|
| Substrate |
L-phenylalanine [CPD:C00079];
tetrahydrobiopterin [CPD:C00272];
O2 [CPD:C00007] |
|---|
| Product |
L-tyrosine [CPD:C00082];
4a-hydroxytetrahydrobiopterin [CPD:C15522] |
|---|
| Cofactor |
Iron [CPD:C00023] |
|---|
| 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 |
PATH: ec00360 Phenylalanine metabolism
PATH: ec00400 Phenylalanine, tyrosine and tryptophan biosynthesis
PATH: ec01100 Metabolic pathways |
|---|
| Orthology |
KO: K00500 phenylalanine-4-hydroxylase |
|---|
| Genes |
HSA: 5053(PAH)
PTR: 741097(PAH)
MCC: 698696(PAH)
MMU: 18478(Pah)
RNO: 24616(Pah)
CFA: 475446(PAH)
BTA: 510583(PAH)
ECB: 100053361
MDO: 100021400
OAA: 100076018
GGA: 408024(PAH)
TGU: 100229122
XTR: 613076
DRE: 378962(pah)
BFO: BRAFLDRAFT_115951
CIN: 100181935
DME: Dmel_CG7399(Hn)
DPO: Dpse_GA20325
DAN: Dana_GF10325
DER: Dere_GG14450
DPE: Dper_GL18039
DSE: Dsec_GM25002
DSI: Dsim_GD14035
DYA: Dyak_GE21640(Dyak_Hn)
DGR: Dgri_GH14976
DMO: Dmoj_GI13137
AGA: AgaP_AGAP005712
CQU: CpipJ_CPIJ002148
AME: 408622
NVI: 100115984
TCA: 655392
API: 100166971
CEL: K08F8.4(pah-1)
CBR: CBG03166
NVE: NEMVE_v1g237576
HMG: 100197101
TAD: TRIADDRAFT_32954
PPP: PHYPADRAFT_5250
CRE: CHLREDRAFT_205945(AAH1)
CME: CMJ066C
MBR: MONBRDRAFT_31770
DDI: DDB_0231664(pah)
TGO: TGME49_012740
TET: TTHERM_00829460
PTM: GSPATT00004497001 GSPATT00031660001
LMA: LmjF28.1280
LIF: LinJ28.1340
LBZ: LbrM28_V2.1380
PTI: PHATRDRAFT_13175
TPS: THAPSDRAFT_bd415(PAH1)
XCC: XCC0156(phhA)
XCB: XC_0165(phhA)
XCA: xccb100_0173(phhA)
XCV: XCV0157(phhA)
XAC: XAC0174(phhA)
XOO: XOO0267(phhA)
XOM: XOO_0243(phhA)
XOP: PXO_03285(phhA)
SML: Smlt0077(phhA)
SMT: Smal_0032(phhA)
VCH: VCA0828(phhA)
VCO: VC0395_0407(phhA)
VCM: VCM66_A0787(phhA)
VCJ: VCD_000497
VVU: VV2_0455(phhA)
VVY: VVA1005(phhA)
VPA: VPA0576(phhA)
VHA: VIBHAR_05421(phhA)
VSP: VS_II1509(phhA)
VEX: VEA_001480
PPR: PBPRB1164(phhA)
PAE: PA0872(phhA)
PAU: PA14_52990(phhA)
PAP: PSPA7_4644(phhA)
PAG: PLES_44441(phhA)
PPU: PP_4490(phhA)
PPF: Pput_1424
PPG: PputGB1_3995(phhA)
PPW: PputW619_3779(phhA)
PST: PSPTO_1822(phhA)
PSB: Psyr_3575(phhA)
PSP: PSPPH_3531(phhA)
PFL: PFL_1611(phhA)
PFO: Pfl01_1499(phhA)
PFS: PFLU4458
PEN: PSEEN3892(phhA)
PMY: Pmen_3112(phhA)
PSA: PST_3562(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)
SLO: Shew_1435(phhA)
SPC: Sputcn32_1386(phhA)
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)
ILO: IL0725(phhA)
CPS: CPS_3766(phhA)
PHA: PSHAa2043(phhA)
PAT: Patl_2999(phhA)
AMC: MADE_02830(phhA)
LPN: lpg2647(phhA)
LPF: lpl2572(phhA)
LPP: lpp2700(phhA)
LPC: LPC_0492(phhA)
HCH: HCH_00956(phhA)
AHA: AHA_1883(phhA)
ASA: ASA_2420(phhA)
KKO: Kkor_1221 Kkor_1520
CVI: CV_3180(phhA)
RSO: RSc3355(phhA)
RPI: Rpic_3549(phhA)
RPF: Rpic12D_3225
REU: Reut_A3387(phhA)
REH: H16_A3678(phhA)
RME: Rmet_3533(phhA)
CTI: RALTA_A3134(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)
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)
BXE: Bxe_A0011(phhA)
BPY: Bphyt_3921(phhA)
BGL: bglu_1g00530
POL: Bpro_0168(phhA) Bpro_4215(phhA)
PNA: Pnap_1117(phhA)
AAV: Aave_4193(phhA)
AJS: Ajs_0518(phhA)
VEI: Veis_2136(phhA)
DAC: Daci_1267(phhA)
DIA: Dtpsy_0534
VAP: Vapar_4768
CTT: CtCNB1_4248
MPT: Mpe_A0347(phhA)
LCH: Lcho_2046(phhA)
BBA: Bd3537(phhA)
ADE: Adeh_2800(phhA)
ACP: A2cp1_2986
AFW: Anae109_2753
ANK: AnaeK_2895
MXA: MXAN_5127(phhA)
SCL: sce5266(phhA)
RBE: RBE_1408(phhA)
RBO: A1I_07840(phhA)
MLO: mlr4831(phhA)
ARA: Arad_8207(phhA)
RET: RHE_CH01742(phhA)
REC: RHECIAT_CH0001823(phhA)
RLE: RL1860(phhA)
RLT: Rleg2_1403(phhA)
RLG: Rleg_1507
CCR: CC_1612(phhA)
CCS: CCNA_01684
CAK: Caul_2208(phhA)
PZU: PHZ_c1409(phhA)
MMR: Mmar10_1853(phhA)
HNE: HNE_1395(phhA)
HBA: Hbal_2665
NAR: Saro_3187(phhA)
SAL: Sala_0553(phhA) Sala_1392(phhA)
ELI: ELI_12050(phhA)
RCE: RC1_3346(phhA)
BAN: BA4586(phhA)
BAR: GBAA4586(phhA)
BAA: BA_5025
BAT: BAS4253(phhA)
BAH: BAMEG_4622
BAI: BAA_4605
BCE: BC4352(phhA)
BCA: BCE_4439(phhA)
BCZ: BCZK4102(phhA)
BCR: BCAH187_A4489
BCB: BCB4264_A4477
BCU: BCAH820_4438
BCG: BCG9842_B0759
BCQ: BCQ_4142(pah)
BCX: BCA_4470
BCY: Bcer98_3076
BTK: BT9727_4091(phhA)
BTL: BALH_3943(phhA)
BWE: BcerKBAB4_4205
ESI: Exig_1060
EAT: EAT1b_2009
NFA: nfa9410(phhA)
BCV: Bcav_3578
TCU: Tcur_3717
SRO: Sros_8337
FRE: Franean1_5444(phhA)
ABA: Acid345_1076(phhA)
ACA: ACP_3318(phhA)
SUS: Acid_4098(phhA)
SRU: SRU_2069(phhA)
CHU: CHU_3025(phhA)
DFE: Dfer_2108
PHE: Phep_3273
GFO: GFO_0233(phhA)
FJO: Fjoh_1902(phhA)
FPS: FP1954(phhA)
RBI: RB2501_09225
CAU: Caur_2799
CAG: Cagg_0605
CHL: Chy400_3030
HAU: Haur_3847
 |
|---|
| Structures |
PDB: 1DMW 1J8T 1J8U 1KW0 1LRM 1LTU 1LTV 1LTZ 1MMK 1MMT
1PAH 1PHZ 1TDW 1TG2 2PAH 2PHM 2V27 2V28 3PAH 4PAH
5PAH 6PAH |
|---|
Reference
Authors
Title
Journal
Organism
|
1 [PMID:5773277]
Guroff G, Rhoads CA.
Phenylalanine hydroxylation by Pseudomonas species (ATCC 11299a).
Nature of the cofactor.
J. Biol. Chem. 244 (1969) 142-6.
Pseudomonas sp. |
|---|
Reference
Authors
Title
Journal
Organism
|
2 [PMID:14404870]
KAUFMAN S.
Studies on the mechanism of the enzymatic conversion of
phenylalanine to tyrosine.
J. Biol. Chem. 234 (1959) 2677-82.
Rattus norvegicus [GN:rno], Ovis aries |
|---|
Reference
Authors
Title
Journal
Organism
|
3 [PMID:13292928]
MITOMA C.
Studies on partially purified phenylalanine hydroxylase.
Arch. Biochem. Biophys. 60 (1956) 476-84.
Rattus norvegicus [GN:rno] |
|---|
Reference
Authors
Title
Journal
Organism
|
4 [PMID:14927641]
UDENFRIEND S, COOPER JR.
The enzymatic conversion of phenylalanine to tyrosine.
J. Biol. Chem. 194 (1952) 503-11.
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno], Canis familiaris
[GN:cfa], Gallus gallus [GN:gga], Cavia porcellus, Oryctolagus
cuniculus |
|---|
Reference
Authors
Title
Journal
Organism
|
5 [PMID:7779797]
Carr RT, Balasubramanian S, Hawkins PC, Benkovic SJ.
Mechanism of metal-independent hydroxylation by Chromobacterium
violaceum phenylalanine hydroxylase.
Biochemistry. 34 (1995) 7525-32.
Chromobacterium violaceum [GN:cvi] |
|---|
Reference
Authors
Title
Journal
Organism
|
6 [PMID:11718561]
Andersen OA, Flatmark T, Hough E.
High resolution crystal structures of the catalytic domain of human
phenylalanine hydroxylase in its catalytically active Fe(II) form
and binary complex with tetrahydrobiopterin.
J. Mol. Biol. 314 (2001) 279-91.
Homo sapiens [GN:hsa] |
|---|
Reference
Authors
Title
Journal
Organism
|
7 [PMID:12096915]
Erlandsen H, Kim JY, Patch MG, Han A, Volner A, Abu-Omar MM, Stevens
RC.
Structural comparison of bacterial and human iron-dependent
phenylalanine hydroxylases: similar fold, different stability and
reaction rates.
J. Mol. Biol. 320 (2002) 645-61.
Homo sapiens [GN:hsa] |
|---|
| Other DBs |
ExplorEnz - The Enzyme Database: 1.14.16.1
IUBMB Enzyme Nomenclature: 1.14.16.1
ExPASy - ENZYME nomenclature database: 1.14.16.1
BRENDA, the Enzyme Database: 1.14.16.1
CAS: 9029-73-6 |
|---|
