KEGG ENZYME: 1.14.14.32

ENZYME: 1.14.14.32

Entry

EC 1.14.14.32               Enzyme

Name

17alpha-hydroxyprogesterone deacetylase;
C-17/C-20 lyase;
17alpha-hydroxyprogesterone acetaldehyde-lyase;
CYP17;
CYP17A1 (gene name);
17alpha-hydroxyprogesterone 17,20-lyase

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

17alpha-hydroxyprogesterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)

Reaction(IUBMB)

(1) 17alpha-hydroxyprogesterone + [reduced NADPH---hemoprotein reductase] + O2 = androstenedione + acetate + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R08518];
(2) 17alpha-hydroxypregnenolone + [reduced NADPH---hemoprotein reductase] + O2 = 3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R08517]

Reaction(KEGG)

R08517 R08518

Substrate

17alpha-hydroxyprogesterone [CPD:C01176];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007];
17alpha-hydroxypregnenolone [CPD:C05138]

Product

androstenedione [CPD:C00280];
acetate [CPD:C00033];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001];
3beta-hydroxyandrost-5-en-17-one [CPD:C01227]

Comment

A microsomal cytochrome P-450 (heme-thiolate) protein that catalyses two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3beta-hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome [2,4]. The enzymes from different organisms differ in their substrate specificity. While the enzymes from pig, hamster, and rat accept both 17alpha-hydroxyprogesterone and 17alpha-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter [1].

History

EC 1.14.14.32 created 1976 as EC 4.1.2.30, transferred 2016 to EC 1.14.14.32

Pathway

ec00140

Steroid hormone biosynthesis

ec01100

Metabolic pathways

Orthology

K00512

steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase

Genes

HSA:	1586(CYP17A1)

PTR:	450141(CYP17A1)

PPS:	100989182(CYP17A1)

GGO:

101152080

PON:

100439753

NLE:

100596228

HMH:

116484149

MCC:	678693(CYP17A1)

MCF:	102133235(CYP17A1)

MTHB:

126962752

MNI:

105478336

CSAB:

103216445(CYP17A1)

CATY:

105581896

PANU:

101026704

TGE:

112630974

MLEU:

105537798

RRO:

104656530

RBB:

108515083

TFN:

117067514

PTEH:

111538851

CANG:

105522771

CJC:	100400572(CYP17A1)

SBQ:

101048584

CIMI:

108306253(CYP17A1)

CSYR:

103251416

MMUR:

105874387

LCAT:

123650072

PCOQ:

105824322

OGA:

100959209

MMU:	13074(Cyp17a1)

MCAL:

110285327

MPAH:

110334801

RNO:	25146(Cyp17a1)

MCOC:

116101357

ANU:

117722327

MUN:

110556807

CGE:

100758683

MAUA:

101831170(Cyp17a1)

PROB:

127233418

PLEU:

114696710

MORG:

121453907

MFOT:

126504210

AAMP:

119802303

NGI:

103744072

HGL:

101726496

CPOC:

100729670

CCAN:

109691327

DORD:

105986673

DSP:

122115926

NCAR:

124985398

OCU:

100346394

OPI:

101532918

TUP:

102472543

GVR:

103596172

CFA:	477807(CYP17A1)

CLUD:

112672259

VVP:

112917782

VLG:

121485837

AML:

100476785

UMR:

103681600

UAH:

113251880

UAR:

123795915

ELK:

111145221

LLV:

125084794

MPUF:

101671806

NVS:

122901070

ORO:

101384623

EJU:

114205173

ZCA:

113923407

MLX:

118025661

NSU:

110589350

LWW:

102745940

FCA:	493967(CYP17A1)

PYU:

121037171

PCOO:

112854651

PBG:

122493194

LRUF:

124507106

PTG:

102966057

PPAD:

109272832

PUC:

125932918

AJU:

106966901

HHV:

120239617

BTA:	112441470 112444495 281739(CYP17A1)

BOM:	102270241 102270532

BIU:	109553214 109579081

BBUB:

102412624 112581551

BBIS:

105002787

CHX:	102182376 102182663(CYP17A1A)

OAS:	105601846(CYP17) 493968(CYP17A1)

ODA:

120873501

CCAD:

122445953 122446740

SSC:	403330(CYP17A1)

CFR:

102519078

CBAI:

105081696

CDK:

105095024

VPC:

102528385

BACU:

103007900

LVE:

103081477

OOR:

101283719

DLE:

111172355

PCAD:

102989171

PSIU:

116741612

NASI:

112393002

ECB:	100034232(CYP17A1)

EPZ:

103558137

EAI:

106838161

MYB:

102259343

MYD:

102761363

MMYO:

118670308

MLF:

102417518

MNA:

107542528

PKL:

118718912

HAI:

109379659

DRO:

112300189

SHON:

118999460

AJM:

119059642

PDIC:

114497592

PHAS:

123828947

MMF:

118631983

RFQ:

117036161

PALE:

102884618

PGIG:

120609141

PVP:

105309652

RAY:

107515566

MJV:

108410298

TOD:	119234280 119234908 119253889

SARA:

101555669

LAV:

100660963

TMU:

101354636

ETF:

101641397

DNM:

101441314

MDO:

100028896

GAS:

123234242

SHR:

100915970

AFZ:

127551531

PCW:

110194957

OAA:

100080906

GGA:	425056(CYP17A1)

PCOC:

116231659

MGP:

100540331

CJO:

107316091

NMEL:

110399428

APLA:

101792920

ACYG:

106031836

AFUL:

116491607

TGU:

100218933

LSR:

110473583

SCAN:

103813852

PMOA:

120502140

OTC:

121341799

PRUF:

121350302

GFR:

102038147

FAB:

101821194

PHI:

102104333

PMAJ:

107206790

CCAE:

111931270

CCW:

104695563

CBRC:

103624562

ETL:

114071768

ZAB:

102070509

ACHL:

103809385

SVG:

106857584

FPG:

101910363

FCH:

102054501

CLV:

102093575

EGZ:

104125602

NNI:

104022305

PLET:

104618241

ACUN:

113481735

TALA:

104366646

PADL:

103916301

AFOR:

103897707

ACHC:

115348606

HALD:

104314833

HLE:

104830098

AGEN:

126042899

GCL:

127017763

CCRI:

104161242

CSTI:

104553046

EHS:

104508633

CMAC:

104485256

MUI:

104536211

FGA:

104083220

GSTE:

104261700

LDI:

104355067

MNB:

103779364

OHA:

104336177

NNT:

104400042

SHAB:

115608953

DPUB:

104307099

PGUU:

104461069

ACAR:

104518499

CPEA:

104390883

AVIT:

104273742

CVF:

104283370

CUCA:

104059767

TEO:

104377577

BRHI:

104495232

AAM:

106494668

AROW:

112967993

NPD:

112957074

TGT:

104565299

DNE:

112989287

SCAM:

104138131

ASN:

102372221

AMJ:	102567971(CYP17A1)

CPOO:

109323822

GGN:

109287570

PSS:

102457785

CMY:

102945773

CPIC:

101933089

TST:

117880996

CABI:

116817103

MRV:

120408966

ACS:	100553634 100553834

PVT:

110077624

SUND:

121925460

PBI:

103063631

PMUR:

107290855

CTIG:

120316288

TSR:

106541312

PGUT:

117678655

VKO:

123024050

PMUA:

114597528

HCG:

128349368

GJA:

107117909

STOW:

125437989

XLA:	100036774(cyp17a1.L)

XTR:	100145650(cyp17a1)

NPR:	108784547 108784564

RTEM:

120946990

BBUF:

121004269 121005522

BGAR:

122942304

DRE:	399692(cyp17a1) 796487(cyp17a2)

SRX:	107707716 107750198

SANH:

107673162 107695149

SGH:	107574436 107588661

CCAR:

109076732 109111078

CAUA:

113041336 113056832 113074379 113085111

CGIB:

127970183 128012018

PPRM:

120479844 120484073 120484098

MAMB:

125260617 125276970 125276972

CIDE:

127504550 127525002

MASI:

127413875 127418618

IPU:	100313515(cyp17) 108275468

PHYP:

113530739 113542020

SMEO:

124396975 124398983

TFD:	113636291 113641757

AMEX:

103036160 111194069

EEE:	113570353 113585465

TRU:	100125766(cyp17a2) 100125798(cyp17a1) 115249663

LCO:	104935158 104936651

NCC:

104957534

CGOB:

115019922

ELY:	117248465 117272651

EFO:	125883749 125904031

PLEP:

121954365 121962489

SLUC:

116034661 116053620

ECRA:

117935140 117960349

ESP:

116686493

PFLV:

114546162 114571983

GAT:	100192329(cyp17a2) 100192330(cyp17a1)

PPUG:

119214573 119222944

MSAM:

119912282 119917252

CUD:	121504405 121510915

ALAT:

119026703 119033497

MZE:	101475441 101477086

ONL:	100702216(cyp17a2) 100703469(cyp17)

OAU:	116332169 116335890

OLA:	100125816(cyp17) 101170547(cyp17a2)

OML:	112156384 112161529

XMA:	102221767 102238057

XCO:	114138338 114157614

XHE:	116712776 116732588 116732589

PRET:

103476526 103480951

PFOR:

103149115 103155787

PLAI:

106934850 106958972

PMEI:

106916522 106928572

GAF:	122820816 122842871

CVG:	107083007 107099069

CTUL:

119773762 119787729

GMU:	124858740 124881307

NFU:	107375507 107396730

KMR:	108239115 108251556

ALIM:

106511002 106515325

NWH:	119417878 119430866

AOCE:

111563640 111579695

MCEP:

125009171 125018366

CSEM:

103387725 103389439

POV:	109634757 109639880

SSEN:

122766283 122781515

HHIP:

117751868 117775903

HSP:	118102904 118119196

LCF:	108892361 108895342

SDU:	111233121 111239202

SLAL:

111661066 111669513

XGL:	120796819 120797261

HCQ:	109516617 109523214

SSCV:

125978579 125992396

BPEC:

110156961 110160276

MALB:

109972947 109973668

BSPL:

114841926 114851252

SASA:

106576693 106592366

STRU:

115193858 115198019

OTW:	112238453 112252939

OMY:	100137017(cyp17a1) 110509408

OGO:	124013898 124040788

ONE:

115136350

SALP:

111951662 112078788

SNH:

120017914

CCLU:

121553719 121559195

ELS:	105006241 105008018

SFM:	108926160 108933747

PKI:	111836781 111859263

AANG:

118218511 118231945

LOC:	102683310 102696373

PSPA:

121321480 121326245

ARUT:

117409034 117415544

PSEX:

120514450

LCM:	102350866 102365866

CMK:

103177103

RTP:

109937010

CPLA:

122561334

BFO:	118425323 118425478

BBEL:

109475258 109487130

AJC:

117119402

DSV:

119442568

RSAN:

119377837

RMP:

119159398

BGT:

106073674

HRJ:	124264060 124275507

CRG:

105337314

PMAX:

117327584

MMER:

123555172 123555557 123558347

DPOL:

127844861 127862613 127862615 127874503

OSN:

115223139

ATEN:

116286226 116287483 116289234 116292213 116292286 116300224 116300467 116304432 116305619 116307262 116308086 116309069

XEN:	124452194 124452197 124452291 124455834

» show all

Reference

1 [PMID:12693981]

Authors

Gilep AA, Estabrook RW, Usanov SA

Title

Molecular cloning and heterologous expression in E. coli of cytochrome P45017alpha. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species.

Journal

Biochemistry (Mosc) 68:86-98 (2003)
DOI:10.1023/a:1022101703670

Sequence

[oas:493968] [ag:AAG02227 AAF65823]

Reference

2 [PMID:9452426]

Authors

Auchus RJ, Lee TC, Miller WL

Title

Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer.

Journal

J Biol Chem 273:3158-65 (1998)
DOI:10.1074/jbc.273.6.3158

Reference

3 [PMID:26668369]

Authors

Mak PJ, Gregory MC, Denisov IG, Sligar SG, Kincaid JR

Title

Unveiling the crucial intermediates in androgen production.

Journal

Proc Natl Acad Sci U S A 112:15856-61 (2015)
DOI:10.1073/pnas.1519376113

Sequence

[hsa:1586]

Reference

4 [PMID:26587646]

Authors

Simonov AN, Holien JK, Yeung JC, Nguyen AD, Corbin CJ, Zheng J, Kuznetsov VL, Auchus RJ, Conley AJ, Bond AM, Parker MW, Rodgers RJ, Martin LL

Title

Mechanistic Scrutiny Identifies a Kinetic Role for Cytochrome b5 Regulation of Human Cytochrome P450c17 (CYP17A1, P450 17A1).

Journal

PLoS One 10:e0141252 (2015)
DOI:10.1371/journal.pone.0141252

Sequence

[hsa:1586]

Reference

5 [PMID:26976652]

Authors

Bhatt MR, Khatri Y, Rodgers RJ, Martin LL.

Title

Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450 17A1).

Journal

J Steroid Biochem Mol Biol 170:2-18 (2017)
DOI:10.1016/j.jsbmb.2016.02.033

Other DBs

ExplorEnz - The Enzyme Database:

1.14.14.32

IUBMB Enzyme Nomenclature:

1.14.14.32

ExPASy - ENZYME nomenclature database:

1.14.14.32

BRENDA, the Enzyme Database:

1.14.14.32

CAS:	62213-24-5

LinkDB

DBGET integrated database retrieval system