KEGG ENZYME: 1.14.14.14

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)

R01840 R02351 R02501 R03087 R04759 R04761 R10511 R10515

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

HSA:	1588(CYP19A1)

PTR:	453433(CYP19A1)

PPS:	100984744(CYP19A1)

GGO:

101137192

PON:

100439777

NLE:

100589061

HMH:

116481527

MCC:	678697(CYP19A1)

MCF:	102117886(CYP19A1)

MTHB:

126959039

MNI:

105490390

CSAB:

103245629(CYP19A1)

CATY:

105588232

PANU:

100997810 116272542

TGE:

112627390

MLEU:

105550746

RRO:

104656901

RBB:

108544828

TFN:

117070662

PTEH:

111552757

CANG:

105502210

CJC:	100411557(CYP19A1)

SBQ:

101051393

CIMI:

108286664(CYP19A1)

CSYR:

103274056

MMUR:

105870707

LCAT:

123622663

PCOQ:

105821381

OGA:

100950881

MMU:	13075(Cyp19a1)

MCAL:

110301208

MPAH:

110328587

RNO:	25147(Cyp19a1)

MCOC:

116073015

ANU:

117699489

MUN:

110549466

CGE:

100769024

MAUA:

101836523

PROB:

127231762

PLEU:

114690371

MORG:

121438190

MFOT:

126486960

AAMP:

119810788

NGI:

103731396

HGL:

101702005

CPOC:

100721069

CCAN:

109675669 109679172

DORD:

105981070

DSP:

122114579

PLOP:

125340435

NCAR:

124977775

OCU:	100328545(CYP19A1)

OPI:

101518265

TUP:

102503106

GVR:

103597966

CFA:	494003(CYP19A1)

CLUD:

112675933

VVP:

112920063

VLG:

121484563

NPO:

129506221

AML:

100464417

UMR:

103676745

UAH:

113269623

UAR:

123801876

ELK:

111138628

LLV:

125105151

MPUF:

101687608

MNP:

131998732

NVS:

122893076

ORO:

101383271

EJU:

114206510

ZCA:

113910201

MLX:

118003757

NSU:

110583928

LWW:

102731614

FCA:	101094932(CYP19A1)

PYU:

121041697

PCOO:

112855925

PBG:

122468647

LRUF:

124508055

PTG:

102962141

PPAD:

109262992

PUC:

125909993

AJU:

106967273

HHV:

120234998

BTA:	281740(CYP19A1)

BOM:

102277416

BIU:

109565118

BBUB:

102392019

BBIS:

104988240

CHX:	100861413(CYP19A1) 102172726

OAS:	100144423(CYP19)

BTAX:

128054322 128054328

ODA:	120852986 120853641

CCAD:

122443608

MBEZ:

129562964

SSC:	403331(CYP19A1) 403332(CYP19A2) 403333(CYP19A3)

CFR:	102519005 116664105

CBAI:

105067585

CDK:	105086637 105106135 116153434

VPC:

102526537

BACU:

103011787 103012080

LVE:	103080853 103081312

OOR:	101270659 101283540

DLE:	111170860 111170861 111171015

PCAD:

102982383 102982657 102995165

PSIU:

116749060 116749147

NASI:

112397422 112397499

ECB:	100009712(CYP19A1)

EPZ:

103546924

EAI:

106838329

MYB:

102253564

MYD:

102753728

MMYO:

118664564

MLF:

102420943

MNA:

107546547

PKL:

118721269

EFUS:

103287429

HAI:

109394298

DRO:

112311730

SHON:

118992519

AJM:

119047586

PDIC:

114493114

PHAS:

123808544

MMF:

118640532

RFQ:

117023688

PALE:

102884354

PGIG:

120623102

PVP:

105288748

RAY:

107519739

MJV:

108388392

TOD:

119238620

SARA:

101552379

LAV:

100669426

TMU:

101350058

ETF:

101657950

DNM:

101411338

MDO:

100031295

GAS:

123234102

SHR:

100929873

AFZ:

127547116

PCW:

110207989

OAA:

100078619

GGA:	414854(CYP19A1)

PCOC:

116244696

MGP:

100549427

CJO:

107318718

TPAI:

128075313

LMUT:

125698403

NMEL:

110403699

APLA:

101791068

ACYG:

106033779

CATA:

118251648

AFUL:

116493626

TGU:	751777(CYP19A1)

LSR:

110474232

SCAN:

103816009

PMOA:

120508816

OTC:

121343497

PRUF:

121354453

GFR:

102039345

FAB:

101821137

OMA:

130257251

PHI:

102100785

PMAJ:

117244929

CCW:

104684007

CBRC:

103621248

ETL:

114057141

ZAB:

102064981

ACHL:

103808252

SVG:

106851780

MMEA:

130575817

HRT:

120758590

FPG:

101920378

FCH:

102056433

CLV:

102090413

EGZ:

104130907

NNI:

104017141

PCRI:

104038312

PLET:

104619051

EHS:

104503710

PCAO:

104042374

ACUN:

113484084

TALA:

104362311

PADL:

103922757

AFOR:

103896611

ACHC:

115341655

HALD:

104317717

HLE:

104834489

AGEN:

126043912

GCL:

127020633

CCRI:

104155487

CSTI:

104550673

CMAC:

104474080

MUI:

104536501

BREG:

104630739

FGA:

104075899

GSTE:

104256103

LDI:

104351247

MNB:

103772445

OHA:

104334585

NNT:

104404179

SHAB:

115612630

DPUB:

104297321

PGUU:

104459145

ACAR:

104519269

CPEA:

104385920

AVIT:

104280735

CVF:

104287055

RTD:

128914969

CUCA:

104054910

TEO:

104380156

BRHI:

104488415

AAM:

106496434

AROW:

112963461

NPD:

112952883

TGT:

104565160

DNE:

112981439

SCAM:

104148271

ASN:

102378511

AMJ:	102566432(CYP19A1)

CPOO:

109309026

GGN:

109288602

PSS:

102459111

CMY:

102946653

CCAY:

125644127

DCC:

119863027

CPIC:

101943325

TST:

117884452

CABI:

116823795

MRV:

120373635

ACS:	100565397(cyp19a1)

PVT:

110077216

SUND:

121934532

PBI:

103056596

PMUR:

107300116

CTIG:

120315257

PGUT:

117674538

APRI:

131184543

PTEX:

113442239

NSS:

113418339

VKO:

123027699

PRAF:

128402012

ZVI:

118092454

HCG:

128335161

GJA:

107122388

STOW:

125424557

EMC:

129345447

XLA:	373656(cyp19a1.L)

XTR:	100036594(cyp19a1)

NPR:

108799589

RTEM:

120931338

BBUF:

120985817 120985818

BGAR:

122927630 122927631

MUO:

115461704

GSH:

117348369

DRE:	30390(cyp19a1a) 60640(cyp19a1b)

SRX:	107746936 107748317

SANH:

107674832 107700584

SGH:	107571340 107588541

CCAR:

109051432 109068452 109072133

CAUA:

113042873 113061867 113082814 113118576

CGIB:

127934323 127977536 128014519

PTET:

122330655 122362496

LROH:

127156350 127181253

OMC:	131524768 131534839

PPRM:

120477771 120485850

MAMB:

125246945 125254507

CIDE:

127500194 127507121

MASI:

127436251 127456148

TROS:

130549838 130551793

MANU:

129419642 129433099

IPU:	100304581 108264511

IFU:	128607126 128618683

PHYP:

113530142 113534440

SMEO:

124392156 124395700

TFD:

113640941

AMEX:

103033668 103038449

CMAO:

118804009 118811907

EEE:	113577298 113584485

CHAR:

105889015 105892489

TRU:	100379639(pfcyp19b-tstr) 101076508(pfcyp19a)

TFS:	130514159 130535683

TNG:	GSTEN00018058G001 GSTEN00025591G001

LCO:	104920192 104932825

NCC:	104960111 104962728

CGOB:

115009664 115024369

ELY:	117258936 117261795

EFO:	125886862 125904127

PLEP:

121947240 121949866

SLUC:

116038508 116054646

ECRA:

117939964 117949645

ESP:	116691016 116693877

PFLV:

114557236 114559505

GAT:	120808695 120811580

PPUG:

119196278 119197603

AFB:	129105323 129108358

CLUM:

117732474 117750439

MSAM:

119890709 119893898

SCHU:

122875290 122875399

CUD:	121515762 121524971

ALAT:

119017644 119023827

MZE:	101468629 106675461 112431276

ONL:	100534396 100708217

OAU:	116311653 116326742

OLA:	100125815(cyp19b) 101174651

OML:	112152291 112161048

XMA:	102231498 102236527

XCO:	114142484 114159678

XHE:	116718071 116736226

PRET:

103462065 103466459

PFOR:

103143597 103156494

PLAI:

106947725 106960953

PMEI:

106912224 106932411

GAF:	122835378 122841295

CVG:	107085369 107096869

CTUL:

119782422 119792512

GMU:	124867322 124881651

NFU:	107373024 107388638

KMR:	108230104 108250266

ALIM:

106521145 106530933 106536387

NWH:	119416354 119423009

AOCE:

111565746 111577263

MCEP:

125005804 125014725

CSEM:

103378914 103380488

POV:	109624148 109624967

SSEN:

122772648 122776510

HHIP:

117754230 117762605 117778658

HSP:	118103743 118109472 118122615 124851147

LCF:	108876685 108887913

SDU:	111223187 111229564

SLAL:

111656853 111666923

XGL:	120793548 120794915

HCQ:	109507515 109525752

SSCV:

125967127 125970121

BPEC:

110169315 110172912

MALB:

109963333 109974150

BSPL:

114852301 114857594

SASA:

106562534 106584746(CYP19B) 106587170(CYP19)

STRU:

115166948 115192897 115203363

OTW:	112241217 112264373

OMY:	110506809 110506810 110521201

OGO:	124017811 124037481

ONE:	115116861 115144680

OKI:	109895311 109897677

OKE:	118359379 118382159

SALP:

112068480 112073830

SNH:	120048793 120048801 120052328

CCLU:

121540733 121579689

ELS:	105018178 105022679

SFM:

108942040

PKI:

111846707

AANG:

118215725

LOC:

102685592

PSPA:

121294903 121299384

ARUT:

117428169 117429562

PSEX:

120539946

LCM:

102348763

CMK:

103186779

RTP:

109931474

CPLA:

122540976

LERI:

129712588

BFO:	118411241 118413506

BBEL:

109471188 109481437

BCOO:

119082474

HSY:

130613325

» 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

LinkDB

DBGET integrated database retrieval system