KEGG   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)
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
HSA1582(CYP8B1)
PTR736962(CYP8B1)
PPS100969929(CYP8B1)
GGO101147556
PON100433242
NLE100605497
MCC717247
MCF102132602(CYP8B1)
CSAB103227471(CYP8B1)
CATY105573840
PANU101002418
TGE112618174
RRO104670956
RBB108532333
TFN117083966
PTEH111555603
CJC100402181(CYP8B1)
SBQ101037790
CSYR103271067
MMUR105874433 105874434
OGA100943894
MMU13124(Cyp8b1)
MCAL110302470
MPAH110327161
RNO81924(Cyp8b1)
MCOC116073386
MUN110554660
CGE100770995
MAUA101841117
PLEU114707690
MORG121464432
AAMP119810738
NGI103747146
CPOC100734566 100734845
CCAN109691739
DORD105996287
DSP122100712
NCAR124969104
OCU100009301(CYP8B1)
OPI101531078
TUP102479742
CFA485619(CYP8B1)
VVP112921604
VLG121478995
AML100464768
UMR103682072
UAH113253657
UAR123778630
ELK111158988
LLV125105604
MPUF101678059
ORO101374077
EJU114212204
ZCA113917882
MLX117999729
FCA101082004
PYU121033533
PBG122492097
PTG102956513
PPAD109248827
AJU106966675
HHV120243596 120243597
BTA538964(CYP8B1)
BIU109576421
BBUB102407955
CHX102173339
OAS101119853
ODA120867731
CCAD122425003
SSC403328(CYP8B1)
CFR102524173
CBAI105061779
CDK105084606
VPC102527710
BACU103000983
LVE103085360
OOR101285967
DLE111164311
PCAD102990799
PSIU116762132
ECB100054970
EPZ103559259
EAI123275565
MYB102245777
MYD102765424
MMYO118668388
MLF102440551
MNA107524319
PKL118715531
HAI109377081
DRO112309563
SHON118976225
AJM119051535
PDIC114501955
PHAS123830673
MMF118632899
RFQ117036539
PALE102877747
PGIG120581963
PVP105290391
RAY107519986
MJV108397210
TOD119258772
SARA101553886
LAV100665029
TMU101356001
DNM101440886
MDO100026525 100026549(CYP8B)
GAS123230807 123254771
SHR100918099 100919664 100926550 105749568
PCW110217059
OAA103166427
GGA425055(CYP8B1)
PCOC116238313
MGP100546803
CJO107308837
NMEL110395135
APLA101797490
ACYG106036789
AFUL116486814
TGU100217899
LSR110474519
SCAN103812684
PMOA120510523
OTC121338124
PRUF121365741
GFR102041987
FAB101809893
PHI102112501
PMAJ107201006
CCAE111925558
CCW104686389
ETL114064499
ZAB102072546
FPG101924073
FCH102052323
CLV102083443
EGZ104124585
NNI104021734
PLET104619451
ACUN113476903
TALA104358666
PADL103924714
ACHC115338885
NPD112953164
DNE112980758
ASN102374897
AMJ102573091(CYP8B1)
CPOO109306069
GGN109291179
PSS102444673
CMY102934823
CPIC101950173
TST117871942
CABI116819555
MRV120399358
ACS100551676 100551876 100562756 100562953 100565509 100565705 100565905 100566106
PVT110091568 110091574 110091575
SUND121932425 121934688 121935162 121935580 121935581
PBI103051222 103065731
PMUR107284342 107284343 107284344 107284346 107284348 107284362
TSR106538485 106538492
PGUT117680087 117680089
VKO123020905 123020984
PMUA114607583 114607705 114607796 114607915
ZVI118091758 118091759 118091944
GJA107106985 107106986 107110695 107112093 107125164
STOW125440698 125441151
XLA108718630(cyp8b1.2.L) 379482(cyp8b1.1.S)
XTR100488015(cyp8b1.2) 100488168(cyp8b1.1)
NPR108788787
RTEM120939823
BBUF121000933
BGAR122929107 122929108
DRE100004274(cyp8b2) 445281(cyp8b1) 447848(cyp8b3)
SRX107711691 107727542
SANH107661909 107671665
SGH107558014 107580338 107593879
CCAR109056773 109056779 109056788
CAUA113038725 113038733 113046101
PPRM120477644 120479271
MAMB125254255
IPU108261592 108268189 108268197
PHYP113524124 113524125
SMEO124387147
TFD113636597
AMEX103039627
EEE113582944 113590803
TRU101070868 101071841 101080232 115248012 115248013
TNGGSTEN00016125G001 GSTEN00016134G001
LCO104917693 104924020
NCC104940932 104941058
CGOB115022806
ELY117269563 117272242 117272243
PLEP121939385 121952022
SLUC116045967
ECRA117954895
PFLV114565114 114570013
GAT120816014
PPUG119206272
MSAM119901973
CUD121519631
ALAT119011762
MZE101474730 106675939 106676194
ONL100693750 109195682 109195683 109195699
OAU116316201 116316225 120434437
OLA101157008
OML112147054
XMA102227191
XCO114147167
XHE116722321
PRET103479711
PFOR103135748
PLAI106948855
PMEI106914255
GAF122841414
CVG107081670
CTUL119794200
GMU124869592
NFU107383849
KMR108241650 108241654
ALIM106533255 106533266
NWH119414670
AOCE111568649 111568654
CSEM103396384
POV109625444 109637167 109638123
SSEN122767875 122767883 122767892 122767898 122767900 122768649 122768658 122779511
HHIP117777688 117777689
HSP118117221 118118273
LCF108883349 108893535
SDU111231161
SLAL111653251
XGL120798539 120802087
HCQ109521313
BPEC110154953 110159864
BSPL114843905 114845031 114845073
SASA106569335 106599887 106599889
OTW112226785 112226786 112260644
OMY110508572 110530492
OGO124010151 124040889 124041735
ONE115102943 115102944 115114571
SALP111956862
SNH120019994 120020264 120055983
ELS105019795 105019804 106024913
SFM108919335 108937621 114910968 114910986
PKI111845862 111845867
AANG118232872
LOC102682983 102694619 102694818
PSPA121311421 121311422 121312642 121312643 121312849 121314286 121314287 121314288 121314311 121314312
ARUT117394306 117394549 117394961 117399933
LCM102357417 102361952
CMK103188298
RTP109923397
MMER123529448
MOREE1B28_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]
Reference
9  [PMID:30465713]
  Authors
Fan L, Joseph JF, Durairaj P, Parr MK, Bureik M.
  Title
Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1.
  Journal
Biol Chem 400:625-628 (2019)
DOI:10.1515/hsz-2018-0379
Other DBs
ExplorEnz - The Enzyme Database: 1.14.14.139
IUBMB Enzyme Nomenclature: 1.14.14.139
ExPASy - ENZYME nomenclature database: 1.14.14.139
BRENDA, the Enzyme Database: 1.14.14.139

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