KEGG ENZYME: 1.14.15.6

ENZYME: 1.14.15.6

Entry

EC 1.14.15.6                Enzyme

Name

cholesterol monooxygenase (side-chain-cleaving);
cholesterol desmolase;
cytochrome P-450scc;
C27-side chain cleavage enzyme;
cholesterol 20-22-desmolase;
cholesterol C20-22 desmolase;
cholesterol side-chain cleavage enzyme;
cholesterol side-chain-cleaving enzyme;
steroid 20-22 desmolase;
steroid 20-22-lyase;
CYP11A1 (gene name)

Class

Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced iron-sulfur protein as one donor, and incorporation of one atom of oxygen into the other donor

Sysname

cholesterol,reduced-adrenodoxin:oxygen oxidoreductase (side-chain-cleaving)

Reaction(IUBMB)

cholesterol + 6 reduced adrenodoxin + 3 O2 + 6 H+ = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction) [RN:R02724];
(1a) cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O [RN:R02723];
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O [RN:R04855];
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O [RN:R03933]

Reaction(KEGG)

R02723 R02724 R03933 R04855;
(other) R01454 R04676 R04854

Substrate

cholesterol [CPD:C00187];
reduced adrenodoxin [CPD:C00662];
O2 [CPD:C00007];
H+ [CPD:C00080];
(22R)-22-hydroxycholesterol [CPD:C05502];
(20R,22R)-20,22-dihydroxy-cholesterol

Product

pregnenolone [CPD:C01953];
4-methylpentanal [CPD:C02373];
oxidized adrenodoxin [CPD:C00667];
H2O [CPD:C00001];
(22R)-22-hydroxycholesterol [CPD:C05502];
(20R,22R)-20,22-dihydroxycholesterol

Comment

A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. The initial source of the electrons is NADPH, which transfers the electrons to the adrenodoxin via EC 1.18.1.6, adrenodoxin-NADP+ reductase.

History

EC 1.14.15.6 created 1983, modified 2013, modified 2014

Pathway

ec00140

Steroid hormone biosynthesis

ec01100

Metabolic pathways

Orthology

K00498

cholesterol monooxygenase (side-chain-cleaving)

Genes

HSA:	1583(CYP11A1)

PTR:	748998(CYP11A1)

PPS:	100979902(CYP11A1)

GGO:

101124697

PON:

100433169

PPYG:

129014548

NLE:

100595981

HMH:

116481899

SSYN:

129482269

MCC:

708065

MCF:	102120640(CYP11A1)

MTHB:

126959982

MNI:

105490949

CSAB:

103245339(CYP11A1)

CATY:

105600069

PANU:

101026207

TGE:

112627656

MLEU:

105530842

RRO:

104672245

RBB:

108531466

TFN:

117070377

PTEH:

111529691

CANG:

105505172

CJC:	100389930(CYP11A1)

SBQ:

101039906

CIMI:

108317488(CYP11A1)

ANAN:

105733476(CYP11A1)

CSYR:

103273593

MMUR:

105862155

LCAT:

123624288

PCOQ:

105807291

OGA:

100951412

MMU:	13070(Cyp11a1)

MCAL:

110301893

MPAH:

110328464

RNO:	29680(Cyp11a1)

MCOC:

116073505

ANU:

117699398

MUN:

110554825

CGE:

100752606

MAUA:

101827747

PROB:

127231817

PLEU:

114690350

MORG:

121445604

MFOT:

126507526

AAMP:

119809739

NGI:

103736867

HGL:

101704598

CPOC:

100716515 100721940

CCAN:

109687652

DORD:

105982351

DSP:	122098454 122098455 122098456 122098457 122098458

PLOP:

125368228

NCAR:

124977503

MMMA:

107137576

OCU:	100345737(CYP11A1)

OPI:

101531464

TUP:

102487565

GVR:

103588064

CFA:	478365(CYP11A1)

CLUD:

112675603

VVP:

112917406

VLG:

121485703

NPO:

129506407

AML:

100474049

UMR:

103678997

UAH:

113240963

UAR:

123790690

ELK:

111153362

LLV:

125105609

MPUF:

101670840

MNP:

132029130

MLK:

131835788

NVS:

122893386

ORO:

101384815

EJU:

114206275

ZCA:

113909555

MLX:

118003325

NSU:

110583983

LWW:

102743616

FCA:	101085980(CYP11A1)

PYU:

121041978

PCOO:

112856210

PBG:

122468436

PVIV:

125168566

LRUF:

124508027

PTG:

102964439

PPAD:

109262704

PUC:

125910141

AJU:

106979451

HHV:

120235769

BTA:	338048(CYP11A1)

BOM:

102282116

BIU:

109575664

BBUB:

102400151

BBIS:

104990998

CHX:	102173131(CYP11A1)

OAS:	100048994(CYP11A1)

BTAX:

128066929

ODA:

120875441

CCAD:

122455135

MBEZ:

129550467

SSC:	403329(CYP11A1)

CFR:

102516700

CBAI:

105069199

CDK:

105087270

VPC:

102526586

BACU:

103011342

BMUS:

118890390

LVE:

103068564

OOR:

101284598

DLE:

111177811

PCAD:

102978389

PSIU:

116749046

NASI:

112410931

ECB:	100034229(CYP11A1)

EPZ:

103567309

EAI:

106842692

MYB:

102241006

MYD:

102765728

MMYO:

118675837

MLF:

102433032

MDT:

132226288

PKL:

118728890

EFUS:

103300197

MNA:

107535212

DRO:

112301926

SHON:

118987828

AJM:

119041324

PDIC:

114492772

PHAS:

123825290

MMF:

118641290

PPAM:

129079756

HAI:

109396248

RFQ:

117022918

PALE:

102894190

PGIG:

120597907

PVP:

105306828

RAY:

107510545

MJV:

108390538

TOD:

119238427

SARA:

101550083

SETR:

126015060

LAV:

100665050

TMU:

101357207

ETF:

101660280

DNM:

101418002

MDO:

100029519

GAS:

123234348

SHR:

100923284

AFZ:

127551988

PCW:

110214023

TVP:	118828559 118829326 118829423

OAA:	100076626 114814661

GGA:	414838(CYP11A1)

PCOC:

116244549

MGP:

100543260

CJO:

107318663

TPAI:

128075179

LMUT:

125698117

NMEL:

110403743

APLA:

101796693

ACYG:

106044184(CYP11A1)

CATA:

118258137

AFUL:

116493636

TGU:	100151695(CYP11A1)

LSR:	110468679 110482567

PMOA:

120504845

OTC:

121343597

PRUF:

121365512

GFR:

102043993

FAB:

101810676

OMA:

130266720

PHI:

102109180

PMAJ:

107209117

ETL:

114059742

ZLE:

135452425

ACHL:

103810611

SVG:

106861058

SATI:

136366834(CYP11A1)

FPG:

101916429

FCH:

102049639

CCRI:

104156830

NNT:

104408617

SHAB:

115612444

ACUN:

113483867

TALA:

104361621

ACHC:

115341287

HLE:

104834370

AGEN:

126043946

GCL:

127020662

CSTI:

104559398

LDI:

104349946

DPUB:

104310199

AVIT:

104273860

BRHI:

104489946

EGZ:

104130717

NNI:

104016802

PCRI:

104027483

PCAO:

104053002

PADL:

103922056

AFOR:

103898612

CLV:

102096337

MUI:

104543313

PGUU:

104465897

EHS:

104506334

CMAC:

104479455

CUCA:

104066308

OHA:

104330625

ACAR:

104527743

CPEA:

104388946

CVF:

104282843

RTD:

128915228

AAM:

106487382

AROW:

112967327

NPD:

112951010

TGT:

104577628

DNE:

112992459

SCAM:

104149167

ASN:

102381626

AMJ:	102569028(CYP11A1)

PSS:

102455057

CMY:

102939633

CCAY:

125644133

DCC:

119862485

CPIC:

101950099

TST:

117884392

CABI:

116821105

MRV:

120372839

ASAO:

132762727

PVT:

110084450

SUND:

121934581

PBI:

103056955

PMUR:

107291917

CTIG:

120305548

TSR:

106553315

APRI:

131184504

PTEX:

113442232

NSS:

113423240

VKO:

123033771

PMUA:

114604069

PRAF:

128421195

ZVI:	118079191 118084488

HCG:

128334996

GJA:

107111326

EMC:

129345167

XLA:	108712986(cyp11a1.S)

XTR:	100495360(cyp11a1)

NPR:

108785561

RTEM:

120931500

BBUF:

120985643

BGAR:

122929707

MUO:

115457552

GSH:

117348607

DRE:	563363(cyp11a2) 80374(cyp11a1.1)

SRX:

107751280

SANH:

107703186

SGH:

107589342

CCAR:

109044858

CAUA:

113043547 113067058

CGIB:

127947488 128014634

PTET:

122330360

LROH:

127156839

OMC:

131534851

PPRM:

120495594

RKG:

130099360

MAMB:

125247683

CIDE:

127507653

CERY:

137014756(cyp11a1.2)

MASI:

127437533

TROS:

130552087 130552089

TDW:

130414250

MANU:

129433626

IPU:	100313513(cyp11a)

IFU:

128618331

PHYP:

113530122

SMEO:

124392299

TFD:

113659881

TVC:

132857451

TRN:

134310151

AMEX:

103021835

CMAO:

118811659

EEE:

113573160

CHAR:

105892393

TRU:

101063139

TFS:

130535831

TNG:	GSTEN00016006G001

LCO:

104924331

NCC:

104966693

TBEN:

117491684

CGOB:

115009784 115009785 115009786 115009787

PGEO:

117447987

GACU:

117538821

EMAC:

134883857

ELY:

117262855

EFO:

125887090

PLEP:

121949937

SLUC:

116038300

ECRA:

117949155

ESP:

116694228

PFLV:

114560394

GAT:

120808883

PPUG:

119196509

AFB:

129107862

CLUM:

117732577

PSWI:

130195235

MSAM:

119894014

SCHU:

122874535

CUD:

121514436

ALAT:

119023908

MZE:

101471001

ONL:

100692956

OAU:

116326291

OLA:	100302421(cyp11a)

OML:

112152747

CSAI:

133444738

XMA:

102235384

XCO:

114151402

XHE:

116729990

PRET:

103466560

PFOR:

103141253

PLAI:

106959477

PMEI:

106927170

GAF:

122835039

PPRL:

129366599

CVG:

107101674

CTUL:

119772345

GMU:

124860809

NFU:

107388733

KMR:

108229950

ALIM:

106514397

NWH:

119416479

AOCE:

111587899

MCEP:

125014867

CSEM:

103380225

POV:

109624184

SSEN:

122775933

HHIP:

117763592

HSP:

118109743

PPLT:

128444488

SMAU:

118315031

LCF:

108886266

SDU:

111228419

SLAL:

111666903

XGL:

120793299

HCQ:

109519394

SSCV:

125970984

SBIA:

133502123

PEE:

133402345

PTAO:

133478445

BPEC:

110163820

MALB:

109971254

BSPL:

114856786

SJO:

128359291

SASA:

106561846(P450scc)

STRU:

115197753

OTW:

112218957

OMY:

110501505

OGO:

124031492

ONE:

115125603

OKI:

109867358

OKE:

118376646

SALP:

112071531

SNH:

120042159

CCLU:

121531238

ELS:

105007422

SFM:

108926637

PKI:

111846669

AANG:

118215491

LOC:

102686734

PSPA:

121298788

ARUT:

117428538 117429302 117963031

PSEX:

120541778

LCM:

102360223

CMK:

103188165

RTP:

109921387

CPLA:

122542498

HOC:

132834715

LERI:

129713472

PMRN:

116938440

BBEL:

109467542 109476488 109476522 109486367

AGB:

108915653

APLN:

108738345

CCRN:

123295827

PJA:

122262122

LJP:	135462469 135466761

» show all

Reference

1 [PMID:1238395]

Authors

Burstein S, Middleditch BS, Gut M

Title

Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation.

Journal

J Biol Chem 250:9028-37 (1975)

Reference

2 [PMID:7217084]

Authors

Hanukoglu I, Spitsberg V, Bumpus JA, Dus KM, Jefcoate CR.

Title

Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover.

Journal

J Biol Chem 256:4321-8 (1981)

Reference

3 [PMID:3011431]

Authors

Hanukoglu I, Hanukoglu Z

Title

Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation.

Journal

Eur J Biochem 157:27-31 (1986)
DOI:10.1111/j.1432-1033.1986.tb09633.x

Reference

4 [PMID:21636783]

Authors

Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW

Title

Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.

Journal

Proc Natl Acad Sci U S A 108:10139-43 (2011)
DOI:10.1073/pnas.1019441108

Sequence

[hsa:1583]

Reference

5 [PMID:21159775]

Authors

Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA

Title

Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1.

Journal

J Biol Chem 286:5607-13 (2011)
DOI:10.1074/jbc.M110.188433

Sequence

[bta:338048]

Other DBs

ExplorEnz - The Enzyme Database:

1.14.15.6

IUBMB Enzyme Nomenclature:

1.14.15.6

ExPASy - ENZYME nomenclature database:

1.14.15.6

BRENDA, the Enzyme Database:

1.14.15.6

CAS:	37292-81-2 440354-98-3

LinkDB

DBGET integrated database retrieval system