KEGG   ENZYME: 1.14.14.14
Entry
EC 1.14.14.14               Enzyme                                 
Name
aromatase;
CYP19A1 (gene name);
estrogen synthetase (incorrect)
Class
Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
Sysname
testosteronel,NADPH---hemoprotein reductase:oxygen oxidoreductase (17beta-estradiol-forming)
Reaction(IUBMB)
(1) testosterone + 3 O2 + 3 [reduced NADPH---hemoprotein reductase] = 17beta-estradiol + formate + 4 H2O + 3 [oxidized NADPH---hemoprotein reductase] (overall reaction) [RN:R10511];
(1a) testosterone + O2 + [reduced NADPH---hemoprotein reductase] = 19-hydroxytestosterone + H2O + [oxidized NADPH---hemoprotein reductase] [RN:R02501];
(1b) 19-hydroxytestosterone + O2 + [reduced NADPH---hemoprotein reductase] = 19-oxotestosterone + 2 H2O + [oxidized NADPH---hemoprotein reductase] [RN:R04761];
(1c) 19-oxotestosterone + O2 + [reduced NADPH---hemoprotein reductase] = 17beta-estradiol + formate + H2O + [oxidized NADPH---hemoprotein reductase] [RN:R03087];
(2) androst-4-ene-3,17-dione + 3 O2 + 3 [reduced NADPH---hemoprotein reductase] = estrone + formate + 4 H2O + 3 [oxidized NADPH---hemoprotein reductase] (overall reaction) [RN:R10515];
(2a) androst-4-ene-3,17-dione + O2 + [reduced NADPH---hemoprotein reductase] = 19-hydroxyandrost-4-ene-3,17-dione + H2O + [oxidized NADPH---hemoprotein reductase] [RN:R01840];
(2b) 19-hydroxyandrost-4-ene-3,17-dione + O2 + [reduced NADPH---hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + 2 H2O + [oxidized NADPH---hemoprotein reductase] [RN:R04759];
(2c) 19-oxoandrost-4-ene-3,17-dione + O2 + [reduced NADPH---hemoprotein reductase] = estrone + formate + H2O + [oxidized NADPH---hemoprotein reductase] [RN:R02351]
Reaction(KEGG)
Substrate
testosterone [CPD:C00535];
O2 [CPD:C00007];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
19-hydroxytestosterone [CPD:C05294];
19-oxotestosterone [CPD:C05295];
androst-4-ene-3,17-dione [CPD:C00280];
19-hydroxyandrost-4-ene-3,17-dione [CPD:C05290];
19-oxoandrost-4-ene-3,17-dione [CPD:C05297]
Product
17beta-estradiol;
formate [CPD:C00058];
H2O [CPD:C00001];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
19-hydroxytestosterone [CPD:C05294];
19-oxotestosterone [CPD:C05295];
estrone [CPD:C00468];
19-hydroxyandrost-4-ene-3,17-dione [CPD:C05290];
19-oxo-androst-4-ene-3,17-dione
Comment
A cytochrome P-450. The enzyme catalyses three sequential hydroxylations of the androgens androst-4-ene-3,17-dione and testosterone, resulting in their aromatization and forming the estrogens estrone and 17beta-estradiol, respectively. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
History
EC 1.14.14.14 created 2013
Pathway
ec00140  Steroid hormone biosynthesis
ec01100  Metabolic pathways
Orthology
K07434  aromatase
Genes
HSA1588(CYP19A1)
PTR453433(CYP19A1)
PPS100984744(CYP19A1)
GGO101137192
PON100439777
NLE100589061
HMH116481527
MCC678697(CYP19A1)
MCF102117886(CYP19A1)
MTHB126959039
MNI105490390
CSAB103245629(CYP19A1)
CATY105588232
PANU100997810 116272542
TGE112627390
MLEU105550746
RRO104656901
RBB108544828
TFN117070662
PTEH111552757
CANG105502210
CJC100411557(CYP19A1)
SBQ101051393
CIMI108286664(CYP19A1)
CSYR103274056
MMUR105870707
LCAT123622663
PCOQ105821381
OGA100950881
MMU13075(Cyp19a1)
MCAL110301208
MPAH110328587
RNO25147(Cyp19a1)
MCOC116073015
ANU117699489
MUN110549466
CGE100769024
MAUA101836523
PROB127231762
PLEU114690371
MORG121438190
MFOT126486960
AAMP119810788
NGI103731396
HGL101702005
CPOC100721069
CCAN109675669 109679172
DORD105981070
DSP122114579
PLOP125340435
NCAR124977775
MMMA107138103
OCU100328545(CYP19A1)
OPI101518265
TUP102503106
GVR103597966
CFA494003(CYP19A1)
CLUD112675933
VVP112920063
VLG121484563
NPO129506221
AML100464417
UMR103676745
UAH113269623
UAR123801876
ELK111138628
LLV125105151
MPUF101687608
MNP131998732
MLK131836281
NVS122893076
ORO101383271
EJU114206510
ZCA113910201
MLX118003757
NSU110583928
LWW102731614
FCA101094932(CYP19A1)
PYU121041697
PCOO112855925
PBG122468647
LRUF124508055
PTG102962141
PPAD109262992
PUC125909993
AJU106967273
HHV120234998
BTA281740(CYP19A1)
BOM102277416
BIU109565118
BBUB102392019
BBIS104988240
CHX100861413(CYP19A1) 102172726
OAS100144423(CYP19)
BTAX128054322 128054328
ODA120852986 120853641
CCAD122443608
MBEZ129562964
SSC403331(CYP19A1) 403332(CYP19A2) 403333(CYP19A3)
CFR102519005 116664105
CBAI105067585
CDK105086637 105106135 116153434
VPC102526537
BACU103011787 103012080
LVE103080853 103081312
OOR101270659 101283540
DLE111170860 111170861 111171015
PCAD102982383 102982657 102995165
PSIU116749060 116749147
NASI112397422 112397499
ECB100009712(CYP19A1)
EPZ103546924
EAI106838329
MYB102253564
MYD102753728
MMYO118664564
MLF102420943
MNA107546547
PKL118721269
EFUS103287429
HAI109394298
DRO112311730
SHON118992519
AJM119047586
PDIC114493114
PHAS123808544
MMF118640532
RFQ117023688
PPAM129063733
PALE102884354
PGIG120623102
PVP105288748
RAY107519739
MJV108388392
TOD119238620
SARA101552379
LAV100669426
TMU101350058
ETF101657950
DNM101411338
MDO100031295
GAS123234102
SHR100929873
AFZ127547116
PCW110207989
OAA100078619
GGA414854(CYP19A1)
PCOC116244696
MGP100549427
CJO107318718
TPAI128075313
LMUT125698403
NMEL110403699
APLA101791068
ACYG106033779
CATA118251648
AFUL116493626
TGU751777(CYP19A1)
LSR110474232
SCAN103816009
PMOA120508816
OTC121343497
PRUF121354453
GFR102039345
FAB101821137
OMA130257251
PHI102100785
PMAJ117244929
CCW104684007
CBRC103621248
ETL114057141
ZAB102064981
ACHL103808252
SVG106851780
MMEA130575817
HRT120758590
FPG101920378
FCH102056433
CLV102090413
EGZ104130907
NNI104017141
PCRI104038312
PLET104619051
EHS104503710
PCAO104042374
ACUN113484084
TALA104362311
PADL103922757
AFOR103896611
ACHC115341655
HALD104317717
HLE104834489
AGEN126043912
GCL127020633
CCRI104155487
CSTI104550673
CMAC104474080
MUI104536501
BREG104630739
FGA104075899
GSTE104256103
LDI104351247
MNB103772445
OHA104334585
NNT104404179
SHAB115612630
DPUB104297321
PGUU104459145
ACAR104519269
CPEA104385920
AVIT104280735
CVF104287055
RTD128914969
CUCA104054910
TEO104380156
BRHI104488415
AAM106496434
AROW112963461
NPD112952883
TGT104565160
DNE112981439
SCAM104148271
ASN102378511
AMJ102566432(CYP19A1)
CPOO109309026
GGN109288602
PSS102459111
CMY102946653
CCAY125644127
DCC119863027
CPIC101943325
TST117884452
CABI116823795
MRV120373635
ACS100565397(cyp19a1)
ASAO132762372
PVT110077216
SUND121934532
PBI103056596
PMUR107300116
CTIG120315257
PGUT117674538
APRI131184543
PTEX113442239
NSS113418339
VKO123027699
PRAF128402012
ZVI118092454
HCG128335161
GJA107122388
STOW125424557
EMC129345447
XLA373656(cyp19a1.L)
XTR100036594(cyp19a1)
NPR108799589
RTEM120931338
BBUF120985817 120985818
BGAR122927630 122927631
MUO115461704
GSH117348369
DRE30390(cyp19a1a) 60640(cyp19a1b)
SRX107746936 107748317
SANH107674832 107700584
SGH107571340 107588541
CCAR109051432 109068452 109072133
CAUA113042873 113061867 113082814 113118576
CGIB127934323 127977536 128014519
PTET122330655 122362496
LROH127156350 127181253
OMC131524768 131534839
PPRM120477771 120485850
RKG130089396 130106434
MAMB125246945 125254507
CIDE127500194 127507121
MASI127436251 127456148
TROS130549838 130551793
TDW130413969 130435397
MANU129419642 129433099
IPU100304581 108264511
IFU128607126 128618683
PHYP113530142 113534440
SMEO124392156 124395700
TFD113640941
TVC132851508 132856826
AMEX103033668 103038449
CMAO118804009 118811907
EEE113577298 113584485
CHAR105889015 105892489
TRU100379639(pfcyp19b-tstr) 101076508(pfcyp19a)
TFS130514159 130535683
TNGGSTEN00018058G001 GSTEN00025591G001
LCO104920192 104932825
NCC104960111 104962728
TBEN117471655 117491915
CGOB115009664 115024369
PGEO117447765
GACU117538803 117549393
ELY117258936 117261795
EFO125886862 125904127
PLEP121947240 121949866
SLUC116038508 116054646
ECRA117939964 117949645
ESP116691016 116693877
PFLV114557236 114559505
GAT120808695 120811580
PPUG119196278 119197603
AFB129105323 129108358
CLUM117732474 117750439
MSAM119890709 119893898
SCHU122875290 122875399
CUD121515762 121524971
ALAT119017644 119023827
MZE101468629 106675461 112431276
ONL100534396 100708217
OAU116311653 116326742
OLA100125815(cyp19b) 101174651
OML112152291 112161048
XMA102231498 102236527
XCO114142484 114159678
XHE116718071 116736226
PRET103462065 103466459
PFOR103143597 103156494
PLAI106947725 106960953
PMEI106912224 106932411
GAF122835378 122841295
CVG107085369 107096869
CTUL119782422 119792512
GMU124867322 124881651
NFU107373024 107388638
KMR108230104 108250266
ALIM106521145 106530933 106536387
NWH119416354 119423009
AOCE111565746 111577263
MCEP125005804 125014725
CSEM103378914 103380488
POV109624148 109624967
SSEN122772648 122776510
HHIP117754230 117762605 117778658
HSP118103743 118109472 118122615 124851147
LCF108876685 108887913
SDU111223187 111229564
SLAL111656853 111666923
XGL120793548 120794915
HCQ109507515 109525752
SSCV125967127 125970121
SBIA133497695 133502032
PEE133399339 133402410
BPEC110169315 110172912
MALB109963333 109974150
BSPL114852301 114857594
SJO128359247 128361936
SASA106562534 106584746(CYP19B) 106587170(CYP19)
STRU115166948 115192897 115203363
OTW112241217 112264373
OMY110506809 110506810 110521201
OGO124017811 124037481
ONE115116861 115144680
OKI109895311 109897677
OKE118359379 118382159
SALP112068480 112073830
SNH120048793 120048801 120052328
CCLU121540733 121579689
ELS105018178 105022679
SFM108942040
PKI111846707
AANG118215725
LOC102685592
PSPA121294903 121299384
ARUT117428169 117429562
PSEX120539946
LCM102348763
CMK103186779
RTP109931474
CPLA122540976
HOC132834197
LERI129712588
PMRN116938464
BFO118411241 118413506
BBEL109471188 109481437
BCOO119082474
HSY130613325
 » show all
Reference
1  [PMID:4370479]
  Authors
Thompson EA Jr, Siiteri PK
  Title
The involvement of human placental microsomal cytochrome P-450 in aromatization.
  Journal
J Biol Chem 249:5373-8 (1974)
Reference
2  [PMID:7217091]
  Authors
Fishman J, Goto J
  Title
Mechanism of estrogen biosynthesis. Participation of multiple enzyme sites in placental aromatase hydroxylations.
  Journal
J Biol Chem 256:4466-71 (1981)
Reference
3  [PMID:3104339]
  Authors
Kellis JT Jr, Vickery LE
  Title
Purification and characterization of human placental aromatase cytochrome P-450.
  Journal
J Biol Chem 262:4413-20 (1987)
Reference
4  [PMID:19129847]
  Authors
Ghosh D, Griswold J, Erman M, Pangborn W
  Title
Structural basis for androgen specificity and oestrogen synthesis in human aromatase.
  Journal
Nature 457:219-23 (2009)
DOI:10.1038/nature07614
  Sequence
[hsa:1588]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.14.14
IUBMB Enzyme Nomenclature: 1.14.14.14
ExPASy - ENZYME nomenclature database: 1.14.14.14
BRENDA, the Enzyme Database: 1.14.14.14

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