KEGG ENZYME: 1.14.15.15

ENZYME: 1.14.15.15

Entry

EC 1.14.15.15               Enzyme

Name

cholestanetriol 26-monooxygenase;
5beta-cholestane-3alpha,7alpha,12alpha-triol 26-hydroxylase;
5beta-cholestane-3alpha,7alpha,12alpha-triol hydroxylase;
cholestanetriol 26-hydroxylase;
sterol 27-hydroxylase;
sterol 26-hydroxylase;
cholesterol 27-hydroxylase;
CYP27A;
CYP27A1;
cytochrome P450 27A1'

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

5beta-cholestane-3alpha,7alpha,12alpha-triol,adrenodoxin:oxygen oxidoreductase (26-hydroxylating)

Reaction(IUBMB)

5beta-cholestane-3alpha,7alpha,12alpha-triol + 6 reduced adrenodoxin + 6 H+ + 3 O2 = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + 6 oxidized adrenodoxin + 4 H2O (overall reaction) [RN:R11142];
(1a) 5beta-cholestane-3alpha,7alpha,12alpha-triol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + 2 oxidized adrenodoxin + H2O [RN:R04807];
(1b) (25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + 2 oxidized adrenodoxin + 2 H2O [RN:R03507];
(1c) (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al + 2 reduced adrenodoxin + 2 H+ + O2 = (25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + 2 oxidized adrenodoxin + H2O [RN:R08761]

Reaction(KEGG)

R03507 R04807 R08761 R11142;
(other) R04806 R08505 R08758 R08759 R08760

Substrate

5beta-cholestane-3alpha,7alpha,12alpha-triol [CPD:C05454];
reduced adrenodoxin [CPD:C00662];
H+ [CPD:C00080];
O2 [CPD:C00007];
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol;
(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al

Product

(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate;
oxidized adrenodoxin [CPD:C00667];
H2O [CPD:C00001];
(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetraol;
(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al

Comment

This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-ene-3beta,7alpha-diol, 7alpha-hydroxycholest-4-en-3-one, and 5beta-cholestane-3alpha,7alpha-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25. 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 1.14.15.15 created 1976 as EC 1.14.13.15, modified 2005, modified 2012, transferred 2016 to EC 1.14.15.15

Pathway

ec00120

Primary bile acid biosynthesis

ec01100

Metabolic pathways

Orthology

K00488

cholestanetriol 26-monooxygenase

K22878

cytochrome P450 daf-9

Genes

HSA:	1593(CYP27A1)

PTR:

459951

PPS:	100989602(CYP27A1)

GGO:

101131774

PON:

100451841

NLE:

100606147

MCC:	700192(CYP27A1)

MCF:	102129822(CYP27A1)

CSAB:

103217882(CYP27A1)

CATY:

105587055

PANU:

100999256

TGE:

112636454

RRO:

104660034

RBB:

108518476

TFN:

117094510

PTEH:

111548691

CJC:	100393783(CYP27A1)

SBQ:

101029011

CSYR:

103261235

MMUR:

105857702

OGA:

100948265

MMU:	104086(Cyp27a1)

MCAL:

110290578

MPAH:

110322436

RNO:	301517(Cyp27a1)

MCOC:

116088582

MUN:

110566769

CGE:

100751584

MAUA:

101842686

PLEU:

114709306

MORG:

121447473

NGI:

103727727

HGL:

101700018

CPOC:

100725007

CCAN:

109679372

DORD:

105987202

DSP:

122107505

NCAR:

124981023

OCU:	100348736(CYP27A1)

OPI:

101518668

TUP:

102471009

CFA:	610489(CYP27A1)

VVP:

112922543

VLG:

121480575

AML:

100480153

UMR:

103662754

UAH:

113250446

UAR:

123779428

ELK:

111142401

LLV:

125095290

MPUF:

101690391

ORO:

101374314

EJU:

114200186

ZCA:

113919618

MLX:

118012034

FCA:

101091962

PYU:

121031077

PBG:

122481780

PTG:

102958835

PPAD:

109265055

AJU:

106970103

HHV:

120232403

BTA:	511960(CYP27A1)

BOM:

102275770

BIU:

109570716

BBUB:

102408966

CHX:

102177672

OAS:

101111528

ODA:

120854365

CCAD:

122426554

SSC:	100126282(CYP27A1)

CFR:

102517717

CBAI:

105064023

CDK:

105096090

VPC:

102536104

BACU:

102999025

LVE:

103080163

OOR:

101288855

DLE:

111171838

PCAD:

102992597

PSIU:

116756897

ECB:	100055936(CYP27A1)

EPZ:

103567914

EAI:

106838458

MYB:

102255768

MYD:

102761397

MMYO:

118661548

MLF:

102424757

MNA:

107524820

PKL:

118717011

HAI:

109380589

DRO:

112307709

SHON:

118975441

AJM:

119056899

PDIC:

114495561

PHAS:

123829715

MMF:

118625177

RFQ:

117025889

PALE:

102883032

PGIG:

120587665

PVP:

105291113

RAY:

107516735

MJV:

108390517

TOD:

119256216

SARA:

101541473

LAV:

100662261

TMU:

101347420

DNM:	101411078 101411838 101423385

MDO:	100011045(CYP27A1)

GAS:

123242736

SHR:

100918281

PCW:

110219429

OAA:

100093207

GGA:	431683(CYP27A1)

PCOC:

116227314

MGP:

100539204

CJO:

107317020

NMEL:

110400531

APLA:

101802865

ACYG:

106039314

AFUL:

116490905

TGU:

100232323

LSR:

110468382

SCAN:

103814667

PMOA:

120496874

OTC:

121335742

PRUF:

121356764

GFR:

102036968

FAB:

101815213

PHI:

102102670

PMAJ:

107207520

CCAE:

111932181

CCW:

104693966

ETL:

114055287

ZAB:

102062293

FPG:

101912381

FCH:

102046779

CLV:

102085729

EGZ:

104132432

NNI:

104010100

ACUN:

113482393

TALA:

116959647

PADL:

103917680

ACHC:

115342636

AAM:

106499073

AROW:

112972033

NPD:

112959865

DNE:

112980321

ASN:

102377709

AMJ:

102562954

CPOO:

109322499

GGN:

109301588

CMY:

102937044

CPIC:

101943409

CABI:

116832589

MRV:

120374801

ACS:

100565025

PVT:

110078231

SUND:

121935066

PBI:

103054208

PMUR:

107292512

TSR:

106540772

PGUT:

117675268

VKO:

123027531

PMUA:

114603027

ZVI:

118090854

GJA:	107116962 107122111

STOW:

125425853 125427460

XLA:	100381137(cyp27a1) 108702937 446987(XB984297.L)

XTR:	100145331 100496109 116407844 594905

NPR:	108783869 108783870 108783871 108783872 108783878 108783885

RTEM:

120944205 120944206 120944214

BBUF:

121007459 121007461 121008616

BGAR:

122944797 122944805 122945772

DRE:	322341(cyp27a1.4) 402831(cyp27a7) 558239(si:ch211-113j14.1) 565876(si:dkey-91i10.3) 723999(zgc:136333) 795106(cyp27a1.2)

SRX:	107705485 107706665 107714212 107723676 107725254 107741910

SANH:

107658292 107659991 107660625 107660626 107677609 107683415

SGH:	107555015 107555356 107555927 107578255 107581419 107584802 107596087

CCAR:

109064887 109072531 109088722 109088733 109088804 109096773 109113433

CAUA:

113050872 113053045 113053331 113092289 113108126 113108393 113108395 113108503

PPRM:

120461532 120461533 120466971(si:dkey-91i10.3) 120491553(si:ch211-113j14.1)

MAMB:

125270463(si:dkey-91i10.3) 125270558 125270559 125270561 125270562 125274236(si:ch211-113j14.1)

IPU:	108261037 108261972 108266301 108266489 108266490 108266491 108272717(si:ch211-113j14.1)

PHYP:

113526131 113526132 113526133 113526134 113526210 113526267 113538157

SMEO:

124380536 124382704 124383131 124383132 124383214(si:dkey-91i10.3) 124392227(si:ch211-113j14.1)

TFD:	113651034(si:ch211-113j14.1) 113654303 113654508(si:dkey-91i10.3) 113654626

AMEX:

103023980 103024291 103027002 103036363

EEE:	113567700 113577222 113586367

TRU:	101062671 101063777 101069976

TNG:	GSTEN00029207G001

LCO:	104934615 104939434 109141591

NCC:	104944399 104954736 104955625

CGOB:

115017336 115026484 115026794

ELY:	117249878(si:ch211-113j14.1) 117251494(si:dkey-91i10.3) 117251800

PLEP:

121949258(si:dkey-91i10.3) 121949317 121962951(si:ch211-113j14.1)

SLUC:

116033996(si:dkey-91i10.3) 116044772(si:ch211-113j14.1)

ECRA:

117939647(si:ch211-113j14.1) 117952801(si:dkey-91i10.3)

PFLV:

114550996 114564588

GAT:	120814973 120814975 120834098

PPUG:

119220421(si:ch211-113j14.1) 119228308 119228466(si:dkey-91i10.3)

MSAM:

119900367(si:ch211-113j14.1) 119903811 119904427(si:dkey-91i10.3)

CUD:	121506513(si:ch211-113j14.1) 121522777 121522982(si:dkey-91i10.3)

ALAT:

119015239(si:ch211-113j14.1) 119025758(si:dkey-91i10.3) 119026140

MZE:	101465003 101473743 101478374

ONL:	100691854 100693469 100705229

OAU:	116314781(si:dkey-91i10.3) 116317150(si:ch211-113j14.1) 116334070

OLA:	101156051 101160538 101175691

OML:	112154786 112155582(si:dkey-91i10.3) 112156772(si:ch211-113j14.1)

XMA:	102225514 102230910 102234678 102234938

XCO:	114140560 114147791 114147794 114148371

XHE:	116715672 116722946 116723684 116723685

PRET:

103456753 103461862 103461863 103478550

PFOR:

103134814 103138135 103154130

PLAI:

106945401 106945403 106949526 106956502

PMEI:

106916312 106919596 106926480

GAF:	122826962 122840052 122840053 122840415(si:dkey-91i10.3)

CVG:	107086204 107086205 107095844 107096820

CTUL:

119774007 119774012 119778495(si:dkey-91i10.3) 119794638(si:ch211-113j14.1)

GMU:	124861938(si:ch211-113j14.1) 124870981 124871015 124871107(si:dkey-91i10.3)

NFU:	107384645 107389662 107396451

KMR:	108238813(si:dkey-91i10.3) 108244283

ALIM:

106511198 106511262 106514257 106532599

NWH:	119419001 119419472(si:dkey-91i10.3) 119429051(si:ch211-113j14.1)

AOCE:

111562629 111568532 111571431 111574457

CSEM:

103380768 103389542

POV:	109637350 109640203 109641449

SSEN:

122765461(si:ch211-113j14.1) 122783812 122784640(si:dkey-91i10.3)

HHIP:

117755070(si:dkey-91i10.3) 117755238 117778068(si:ch211-113j14.1)

HSP:	118103627(si:ch211-113j14.1) 118120133 118120203(si:dkey-91i10.3)

LCF:	108873048 108897118 108897170

SDU:	111218457 111218691 111222696

SLAL:

111653799 111667407 111672420

XGL:	120798148(si:ch211-113j14.1) 120801357(si:dkey-91i10.3) 120801379

HCQ:	109517561 109519132 109528391

BPEC:

110165678 110166041 110171370

MALB:

109955654 109972640 109974026

BSPL:

114845813(si:ch211-113j14.1) 114846707 114846743(si:dkey-91i10.3)

SASA:

106574240 106575170 106586130 106586420 106586421

OTW:	112225125 112235263 112238608(si:dkey-91i10.3) 112253824 112266509

OMY:	110495869 110501573 110520006 110520277(si:dkey-91i10.3) 110527483

OGO:	124008274 124010863 124041765 124043781 124043995(si:dkey-91i10.3)

ONE:	115107908 115110822 115129706 115133470 115136440

SALP:

111953394 111959818 111970920 111973814

SNH:	120033627(si:ch211-113j14.1) 120050736 120058201 120058325 120058328 120064454

ELS:	105016129 105016181 105019951

SFM:	108928920 108936404

PKI:	111840728 111851734

AANG:

118214017(si:ch211-113j14.1) 118222144(si:dkey-91i10.3) 118222523 118223580

LOC:	102687850 102689682 102690084 102695871

PSPA:

121322499 121323017 121323418 121323529(si:dkey-91i10.3)

ARUT:

117404073 117408072 117411922 117426218

LCM:	102347924 102352926 102355859(EAF2) 102357152

CMK:	103189020(si:dkey-91i10.3)

RTP:	109912644 109924020

BBEL:

109482768

CEL:	CELE_T13C5.1(daf-9)

CBR:	CBG_10440 CBG_14860(Cbr-daf-9)

BMY:	BM_BM2557(Bma-daf-9)

LOA:	LOAG_03116

GAE:	121371591 121371592 121372413

HRJ:	124282300 124282301

ATEN:

116287947

» show all

Reference

1 [PMID:5914340]

Authors

Masui T, Herman R, Staple E.

Title

The oxidation of 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha, 26-tetraol to 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol-26-oic acid via 5-beta-cholestane-3-alpha, 7-alpha, 12-alpha-triol-26-al by rat liver.

Journal

Biochim Biophys Acta 117:266-8 (1966)
DOI:10.1016/0304-4165(66)90177-2

Reference

2 [PMID:4388637]

Authors

Okuda K, Hoshita N.

Title

Oxidation of 5-beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol by rat-liver mitochondria.

Journal

Biochim Biophys Acta 164:381-8 (1968)
DOI:10.1016/0005-2760(68)90162-8

Reference

3 [PMID:6423637]

Authors

Wikvall K.

Title

Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C27-steroids.

Journal

J Biol Chem 259:3800-4 (1984)

Reference

4 [PMID:2722778]

Authors

Andersson S, Davis DL, Dahlback H, Jornvall H, Russell DW

Title

Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.

Journal

J Biol Chem 264:8222-9 (1989)

Sequence

[ocu:100348736]

Reference

5 [PMID:2322231]

Authors

Dahlback H, Holmberg I

Title

Oxidation of 5 beta-cholestane-3 alpha,7 alpha, 12 alpha-triol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by cytochrome P-450(26) from rabbit liver mitochondria.

Journal

Biochem Biophys Res Commun 167:391-5 (1990)
DOI:10.1016/0006-291X(90)92034-W

Reference

6 [PMID:8496170]

Authors

Holmberg-Betsholtz I, Lund E, Bjorkhem I, Wikvall K.

Title

Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid.

Journal

J Biol Chem 268:11079-85 (1993)

Reference

7 [PMID:9660774]

Authors

Pikuleva IA, Babiker A, Waterman MR, Bjorkhem I

Title

Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways.

Journal

J Biol Chem 273:18153-60 (1998)
DOI:10.1074/jbc.273.29.18153

Reference

8 [PMID:10512735]

Authors

Furster C, Bergman T, Wikvall K.

Title

Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria.

Journal

Biochem Biophys Res Commun 263:663-6 (1999)
DOI:10.1006/bbrc.1999.1426

Reference

9 [PMID:11412116]

Authors

Pikuleva IA, Puchkaev A, Bjorkhem I

Title

Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1.

Journal

Biochemistry 40:7621-9 (2001)
DOI:10.1021/bi010193i

Sequence

[hsa:1593]

Other DBs

ExplorEnz - The Enzyme Database:

1.14.15.15

IUBMB Enzyme Nomenclature:

1.14.15.15

ExPASy - ENZYME nomenclature database:

1.14.15.15

BRENDA, the Enzyme Database:

1.14.15.15

CAS:	52227-77-7

LinkDB

DBGET integrated database retrieval system