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:

GGO:

PON:

NLE:

MCC:

MCF:

CSAB:

103227471(CYP8B1)

CATY:

RRO:

RBB:

TFN:

CJC:	100402181(CYP8B1)

SBQ:

101037790

MMUR:

105874433 105874434

MMU:	13124(Cyp8b1)

MCAL:

110302470

MPAH:

110327161

RNO:	81924(Cyp8b1)

MCOC:

MUN:

CGE:

PLEU:

NGI:

CCAN:

OCU:	100009301(CYP8B1)

TUP:

102479742

CFA:	485619(CYP8B1)

VVP:

AML:

UMR:

UAH:

ORO:

ELK:

MPUF:

EJU:

FCA:

PTG:

PPAD:

AJU:

BTA:	538964(CYP8B1)

BIU:

BBUB:

CHX:

OAS:

SSC:	403328(CYP8B1)

CFR:

CDK:

BACU:

LVE:

OOR:

DLE:

PCAD:

ECB:

EPZ:

EAI:

MYB:

MYD:

MMYO:

MNA:

HAI:

DRO:

SHON:

AJM:

MMF:

PALE:

RAY:

MJV:

LAV:

TMU:

MDO:	100026525 100026549(CYP8B)

SHR:	100918099 100919664 100926550 105749568

PCW:

110217059

OAA:

103166427

GGA:	425055(CYP8B1)

MGP:

CJO:

NMEL:

APLA:

ACYG:

TGU:

LSR:

SCAN:

GFR:

FAB:

PHI:

PMAJ:

CCAE:

CCW:

ETL:

FPG:

FCH:

CLV:

EGZ:

NNI:

ACUN:

PADL:

ASN:

AMJ:	102573091(CYP8B1)

PSS:

102444673

CMY:

102934823

CPIC:

101950173

ACS:	100551676 100551876 100562756 100562953 100565509 100565705 100565905 100566106

PVT:	110091568 110091574 110091575

PBI:	103051222 103065731

PMUR:

107284342 107284343 107284344 107284346 107284348 107284362

TSR:	106538485 106538492

PMUA:

114607583 114607705 114607796 114607915

GJA:	107106985 107106986 107110695 107112093 107125164

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

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

NPR:

108788787

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

SRX:	107711691 107727542

SANH:

107661909 107671665

SGH:	107558014 107580338 107593879

CCAR:

109056773 109056779 109056788

IPU:	108261592 108268189 108268197

PHYP:

113524124 113524125

AMEX:

103039627

EEE:	113582944 113590803

TRU:	101070868 101071841 101080232 115248012 115248013

TNG:	GSTEN00016125G001 GSTEN00016134G001

LCO:	104917693 104924020

NCC:	104940932 104941058

MZE:	101474730 106675939 106676194

ONL:	100693750 109195682 109195683 109195699

OLA:

XMA:

XCO:

PRET:

CVG:

NFU:

KMR:	108241650 108241654

ALIM:

106533255 106533266

AOCE:

111568649 111568654

CSEM:

103396384

POV:	109625444 109637167 109638123

LCF:	108883349 108893535

SDU:

SLAL:

HCQ:

BPEC:

SASA:

106569335 106599887 106599889

OTW:	112226785 112226786 112260644

SALP:

111956862

ELS:	105019795 105019804 106024913

SFM:	108919335 108937621 114910968 114910986

PKI:	111845862 111845867

LCM:	102357417 102361952

CMK:

103188298

RTP:

109923397

» 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]