KEGG ENZYME: 1.14.14.139

ENZYME: 1.14.14.139

Entry

EC 1.14.14.139              Enzyme

Name

5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase;
5beta-cholestane-3alpha,7alpha-diol 12alpha-monooxygenase;
sterol 12alpha-hydroxylase (ambiguous);
CYP8B1;
cytochrome P450 8B1;
7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase;
7alpha-hydroxy-4-cholesten-3-one 12alpha-monooxygenase;
chenodeoxycholate 12alpha monooxygenase

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

5beta-cholestane-3alpha,7alpha-diol,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (12alpha-hydroxylating)

Reaction(IUBMB)

(1) 5beta-cholestane-3alpha,7alpha-diol + [reduced NADPH---hemoprotein reductase] + O2 = 5beta-cholestane-3alpha,7alpha,12alpha-triol + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R07204];
(2) 7alpha-hydroxycholest-4-en-3-one + [reduced NADPH---hemoprotein reductase] + O2 = 7alpha,12alpha-dihydroxycholest-4-en-3-one + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R04826];
(3) chenodeoxycholate + [reduced NADPH---hemoprotein reductase] + O2 = cholate + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R12550]

Reaction(KEGG)

R04826 R07204 R12550

Substrate

5beta-cholestane-3alpha,7alpha-diol [CPD:C05452];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007];
7alpha-hydroxycholest-4-en-3-one [CPD:C05455];
chenodeoxycholate [CPD:C02528]

Product

5beta-cholestane-3alpha,7alpha,12alpha-triol [CPD:C05454];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001];
7alpha,12alpha-dihydroxycholest-4-en-3-one;
cholate [CPD:C00695]

Comment

A cytochrome P-450 (heme-thiolate) protein found in mammals. This is the key enzyme in the biosynthesis of the bile acid cholate. The enzyme can also hydroxylate 5beta-cholestane-3alpha,7alpha-diol at the 25 and 26 position, but to a lesser extent [2].

History

EC 1.14.14.139 created 2005 as EC 1.14.13.96, transferred 2018 to EC 1.14.14.139 (EC 1.14.18.8 created 2005 as EC 1.14.13.95, transferred 2015 to EC 1.14.18.8, incorporated 2020) , modified 2020

Pathway

ec00120

Primary bile acid biosynthesis

ec01100

Metabolic pathways

Orthology

K07431

sterol 12-alpha-hydroxylase

Genes

HSA:	1582(CYP8B1)

PTR:	736962(CYP8B1)

PPS:	100969929(CYP8B1)

GGO:

101147556

PON:

100433242

NLE:

100605497

MCC:

717247

MCF:	102132602(CYP8B1)

CSAB:

103227471(CYP8B1)

CATY:

105573840

PANU:

101002418

TGE:

112618174

RRO:

104670956

RBB:

108532333

TFN:

117083966

PTEH:

111555603

CJC:	100402181(CYP8B1)

SBQ:

101037790

CSYR:

103271067

MMUR:

105874433 105874434

OGA:

100943894

MMU:	13124(Cyp8b1)

MCAL:

110302470

MPAH:

110327161

RNO:	81924(Cyp8b1)

MCOC:

116073386

MUN:

110554660

CGE:

100770995

MAUA:

101841117

PLEU:

114707690

MORG:

121464432

AAMP:

119810738

NGI:

103747146

CPOC:

100734566 100734845

CCAN:

109691739

DORD:

105996287

DSP:

122100712

NCAR:

124969104

OCU:	100009301(CYP8B1)

OPI:

101531078

TUP:

102479742

CFA:	485619(CYP8B1)

VVP:

112921604

VLG:

121478995

AML:

100464768

UMR:

103682072

UAH:

113253657

UAR:

123778630

ELK:

111158988

LLV:

125105604

MPUF:

101678059

ORO:

101374077

EJU:

114212204

ZCA:

113917882

MLX:

117999729

FCA:

101082004

PYU:

121033533

PBG:

122492097

PTG:

102956513

PPAD:

109248827

AJU:

106966675

HHV:	120243596 120243597

BTA:	538964(CYP8B1)

BIU:

109576421

BBUB:

102407955

CHX:

102173339

OAS:

101119853

ODA:

120867731

CCAD:

122425003

SSC:	403328(CYP8B1)

CFR:

102524173

CBAI:

105061779

CDK:

105084606

VPC:

102527710

BACU:

103000983

LVE:

103085360

OOR:

101285967

DLE:

111164311

PCAD:

102990799

PSIU:

116762132

ECB:

100054970

EPZ:

103559259

EAI:

123275565

MYB:

102245777

MYD:

102765424

MMYO:

118668388

MLF:

102440551

MNA:

107524319

PKL:

118715531

HAI:

109377081

DRO:

112309563

SHON:

118976225

AJM:

119051535

PDIC:

114501955

PHAS:

123830673

MMF:

118632899

RFQ:

117036539

PALE:

102877747

PGIG:

120581963

PVP:

105290391

RAY:

107519986

MJV:

108397210

TOD:

119258772

SARA:

101553886

LAV:

100665029

TMU:

101356001

DNM:

101440886

MDO:	100026525 100026549(CYP8B)

GAS:	123230807 123254771

SHR:	100918099 100919664 100926550 105749568

PCW:

110217059

OAA:

103166427

GGA:	425055(CYP8B1)

PCOC:

116238313

MGP:

100546803

CJO:

107308837

NMEL:

110395135

APLA:

101797490

ACYG:

106036789

AFUL:

116486814

TGU:

100217899

LSR:

110474519

SCAN:

103812684

PMOA:

120510523

OTC:

121338124

PRUF:

121365741

GFR:

102041987

FAB:

101809893

PHI:

102112501

PMAJ:

107201006

CCAE:

111925558

CCW:

104686389

ETL:

114064499

ZAB:

102072546

FPG:

101924073

FCH:

102052323

CLV:

102083443

EGZ:

104124585

NNI:

104021734

PLET:

104619451

ACUN:

113476903

TALA:

104358666

PADL:

103924714

ACHC:

115338885

NPD:

112953164

DNE:

112980758

ASN:

102374897

AMJ:	102573091(CYP8B1)

CPOO:

109306069

GGN:

109291179

PSS:

102444673

CMY:

102934823

CPIC:

101950173

TST:

117871942

CABI:

116819555

MRV:

120399358

ACS:	100551676 100551876 100562756 100562953 100565509 100565705 100565905 100566106

PVT:	110091568 110091574 110091575

SUND:

121932425 121934688 121935162 121935580 121935581

PBI:	103051222 103065731

PMUR:

107284342 107284343 107284344 107284346 107284348 107284362

TSR:	106538485 106538492

PGUT:

117680087 117680089

VKO:	123020905 123020984

PMUA:

114607583 114607705 114607796 114607915

ZVI:	118091758 118091759 118091944

GJA:	107106985 107106986 107110695 107112093 107125164

STOW:

125440698 125441151

XLA:	108718630(cyp8b1.2.L) 379482(cyp8b1.1.S)

XTR:	100488015(cyp8b1.2) 100488168(cyp8b1.1)

NPR:

108788787

RTEM:

120939823

BBUF:

121000933

BGAR:

122929107 122929108

DRE:	100004274(cyp8b2) 445281(cyp8b1) 447848(cyp8b3)

SRX:	107711691 107727542

SANH:

107661909 107671665

SGH:	107558014 107580338 107593879

CCAR:

109056773 109056779 109056788

CAUA:

113038725 113038733 113046101

PPRM:

120477644 120479271

MAMB:

125254255

IPU:	108261592 108268189 108268197

PHYP:

113524124 113524125

SMEO:

124387147

TFD:

113636597

AMEX:

103039627

EEE:	113582944 113590803

TRU:	101070868 101071841 101080232 115248012 115248013

TNG:	GSTEN00016125G001 GSTEN00016134G001

LCO:	104917693 104924020

NCC:	104940932 104941058

CGOB:

115022806

ELY:	117269563 117272242 117272243

PLEP:

121939385 121952022

SLUC:

116045967

ECRA:

117954895

PFLV:

114565114 114570013

GAT:

120816014

PPUG:

119206272

MSAM:

119901973

CUD:

121519631

ALAT:

119011762

MZE:	101474730 106675939 106676194

ONL:	100693750 109195682 109195683 109195699

OAU:	116316201 116316225 120434437

OLA:

101157008

OML:

112147054

XMA:

102227191

XCO:

114147167

XHE:

116722321

PRET:

103479711

PFOR:

103135748

PLAI:

106948855

PMEI:

106914255

GAF:

122841414

CVG:

107081670

CTUL:

119794200

GMU:

124869592

NFU:

107383849

KMR:	108241650 108241654

ALIM:

106533255 106533266

NWH:

119414670

AOCE:

111568649 111568654

CSEM:

103396384

POV:	109625444 109637167 109638123

SSEN:

122767875 122767883 122767892 122767898 122767900 122768649 122768658 122779511

HHIP:

117777688 117777689

HSP:	118117221 118118273

LCF:	108883349 108893535

SDU:

111231161

SLAL:

111653251

XGL:	120798539 120802087

HCQ:

109521313

BPEC:

110154953 110159864

BSPL:

114843905 114845031 114845073

SASA:

106569335 106599887 106599889

OTW:	112226785 112226786 112260644

OMY:	110508572 110530492

OGO:	124010151 124040889 124041735

ONE:	115102943 115102944 115114571

SALP:

111956862

SNH:	120019994 120020264 120055983

ELS:	105019795 105019804 106024913

SFM:	108919335 108937621 114910968 114910986

PKI:	111845862 111845867

AANG:

118232872

LOC:	102682983 102694619 102694818

PSPA:

121311421 121311422 121312642 121312643 121312849 121314286 121314287 121314288 121314311 121314312

ARUT:

117394306 117394549 117394961 117399933

LCM:	102357417 102361952

CMK:

103188298

RTP:

109923397

MMER:

123529448

E1B28_009492

» show all

Reference

1 [PMID:6766451]

Authors

Hansson R, Wikvall K.

Title

Hydroxylations in biosynthesis and metabolism of bile acids. Catalytic properties of different forms of cytochrome P-450.

Journal

J Biol Chem 255:1643-9 (1980)

Reference

2 [PMID:6811268]

Authors

Hansson R, Wikvall K.

Title

Hydroxylations in biosynthesis of bile acids. Cytochrome P-450 LM4 and 12alpha-hydroxylation of 5beta-cholestane-3alpha, 7alpha-diol.

Journal

Eur J Biochem 125:423-9 (1982)
DOI:10.1111/j.1432-1033.1982.tb06700.x

Reference

3 [PMID:1400444]

Authors

Ishida H, Noshiro M, Okuda K, Coon MJ

Title

Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase.

Journal

J Biol Chem 267:21319-23 (1992)

Reference

4 [PMID:8943286]

Authors

Eggertsen G, Olin M, Andersson U, Ishida H, Kubota S, Hellman U, Okuda KI, Bjorkhem I.

Title

Molecular cloning and expression of rabbit sterol 12alpha-hydroxylase.

Journal

J Biol Chem 271:32269-75 (1996)
DOI:10.1074/jbc.271.50.32269

Sequence

[ocu:100009301]

Reference

5 [PMID:14643796]

Authors

Lundell K, Wikvall K.

Title

Gene structure of pig sterol 12alpha-hydroxylase (CYP8B1) and expression in fetal liver: comparison with expression of taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21).

Journal

Biochim Biophys Acta 1634:86-96 (2003)
DOI:10.1016/j.bbalip.2003.09.002

Sequence

[ssc:403328]

Reference

6 [PMID:10747975]

Authors

del Castillo-Olivares A, Gil G.

Title

Alpha 1-fetoprotein transcription factor is required for the expression of sterol 12alpha -hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription.

Journal

J Biol Chem 275:17793-9 (2000)
DOI:10.1074/jbc.M000996200

Reference

7 [PMID:12069850]

Authors

Yang Y, Zhang M, Eggertsen G, Chiang JY.

Title

On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha.

Journal

Biochim Biophys Acta 1583:63-73 (2002)
DOI:10.1016/S1388-1981(02)00186-5

Reference

8 [PMID:12543708]

Authors

Russell DW

Title

The enzymes, regulation, and genetics of bile acid synthesis.

Journal

Annu Rev Biochem 72:137-74 (2003)
DOI:10.1146/annurev.biochem.72.121801.161712

Sequence

[hsa:1582] [mmu:13124]