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:

PPS:

GGO:

PON:

NLE:

MCC:	700192(CYP27A1)

MCF:	102129822(CYP27A1)

CSAB:

103217882(CYP27A1)

RRO:

104660034

RBB:

108518476

CJC:	100393783(CYP27A1)

SBQ:

101029011

MMU:	104086(Cyp27a1)

MCAL:

110290578

MPAH:

110322436

RNO:	301517(Cyp27a1)

MUN:

CGE:

NGI:

HGL:

CCAN:

OCU:	100348736(CYP27A1)

TUP:

102471009

CFA:	610489(CYP27A1)

VVP:

AML:

UMR:

UAH:

ORO:

ELK:

FCA:

PTG:

PPAD:

AJU:

BTA:	511960(CYP27A1)

BOM:

BIU:

BBUB:

CHX:

OAS:

SSC:	100126282(CYP27A1)

CFR:

CDK:

BACU:

LVE:

OOR:

DLE:

PCAD:

ECB:	100055936(CYP27A1)

EPZ:

EAI:

MYB:

MYD:

MNA:

HAI:

DRO:

PALE:

RAY:

MJV:

LAV:

TMU:

MDO:	100011045(CYP27A1)

SHR:

100918281

PCW:

110219429

OAA:

100093207

GGA:	431683(CYP27A1)

MGP:

CJO:

NMEL:

APLA:

ACYG:

TGU:

LSR:

SCAN:

GFR:

FAB:

PHI:

PMAJ:

CCAE:

CCW:

ETL:

FPG:

FCH:

CLV:

EGZ:

NNI:

ACUN:

PADL:

AAM:

ASN:

AMJ:

CMY:

CPIC:

ACS:

PVT:

PBI:

PMUR:

TSR:

PMUA:

GJA:	107116962 107122111

XLA:	100381137(cyp27a1) 108702937 446987(LOC100145331.L) 733412

XTR:	100145331 100496109 116407844 594905

NPR:	108783869 108783870 108783871 108783872 108783878 108783885

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

IPU:	108261037 108261972(CYP27A16) 108266301 108266489(CYP27A15) 108266490(CYP27A17) 108266491 108272717

PHYP:

113526131 113526132 113526133 113526134 113526210 113526267 113538157

AMEX:

103023980 103024291 103027002 103036363

EEE:	113567700 113577222 113586367

TRU:	101062671 101063777 101069976

TNG:	GSTEN00029207G001

LCO:	104934615 104939434 109141591

NCC:	104944399 104954736 104955625

MZE:	101465003 101473743 101478374

ONL:	100691854 100693469 100705229

OLA:	101156051 101160538 101175691

XMA:	102225514 102230910 102234678 102234938

XCO:	114140560 114147791 114147794 114148371

PRET:

103456753 103461862 103461863 103478550

CVG:	107086204 107086205 107095844 107096820

NFU:	107384645 107389662 107396451

KMR:	108238813 108244283

ALIM:

106511198 106511262 106514257 106532599

AOCE:

111562629 111568532 111571431 111574457

CSEM:

103380768 103389542

POV:	109637350 109640203 109641449

LCF:	108873048 108897118 108897170

SDU:	111218457 111218691 111222696

SLAL:

111653799 111667407 111672420

HCQ:	109517561 109519132 109528391

BPEC:

110165678 110166041 110171370

MALB:

109955654 109972640 109974026

SASA:

106574240 106575170 106581857 106586130 106586420 106586421

OTW:	112225125 112238608 112253824 112253857 112266509

SALP:

111953394 111959818 111970920 111973814

ELS:	105016129 105016181 105019951

SFM:	108928920 108936404

PKI:	111840728 111851734

LCM:	102347924 102352926 102355859(EAF2) 102357152

CMK:

103189020

RTP:	109912644 109924020

BFO:

118417589

SKO:

100370591

CEL:	CELE_T13C5.1(daf-9)

CBR:	CBG14860(Cbr-daf-9)

BMY:

Bm1_42095

LOA:	LOAG_03116

NVE:	5512032 5513719 5513720 5520494

EPA:	110242117 110253216

ADF:	107358538 107358539

PDAM:

113677842 113678709 113684056

SPIS:

111338895

DGT:	114516839 114518442 114523169 114531267

TAD:	TRIADDRAFT_25150 TRIADDRAFT_53411 TRIADDRAFT_56953 TRIADDRAFT_56983

AQU:	100640201 100640453

SPAR:

SPRG_05930

NGR:	NAEGRDRAFT_79810

» 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