KEGG   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)
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
GGO: 101131774
PON: 100451841
NLE: 100606147
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: 110566769
CGE: 100751584
NGI: 103727727
HGL: 101700018
CCAN: 109679372
OCU: 100348736(CYP27A1)
TUP: 102471009
CFA: 610489(CYP27A1)
VVP: 112922543
AML: 100480153
UMR: 103662754
UAH: 113250446
ORO: 101374314
ELK: 111142401
FCA: 101091962
PTG: 102958835
PPAD: 109265055
AJU: 106970103
BTA: 511960(CYP27A1)
BOM: 102275770
BIU: 109570716
BBUB: 102408966
CHX: 102177672
OAS: 101111528
SSC: 100126282(CYP27A1)
CFR: 102517717
CDK: 105096090
BACU: 102999025
LVE: 103080163
OOR: 101288855
DLE: 111171838
PCAD: 102992597
ECB: 100055936(CYP27A1)
EPZ: 103567914
EAI: 106838458
MYB: 102255768
MYD: 102761397
MNA: 107524820
HAI: 109380589
DRO: 112307709
PALE: 102883032
RAY: 107516735
MJV: 108390517
LAV: 100662261
TMU: 101347420
MDO: 100011045(CYP27A1)
SHR: 100918281
PCW: 110219429
OAA: 100093207
GGA: 431683(CYP27A1)
MGP: 100539204
CJO: 107317020
NMEL: 110400531
APLA: 101802865
ACYG: 106039314
TGU: 100232323
LSR: 110468382
SCAN: 103814667
GFR: 102036968
FAB: 101815213
PHI: 102102670
PMAJ: 107207520
CCAE: 111932181
CCW: 104693966
ETL: 114055287
FPG: 101912381
FCH: 102046779
CLV: 102085729
EGZ: 104132432
NNI: 104010100
ACUN: 113482393
PADL: 103917680
AAM: 106499073
ASN: 102377709
AMJ: 102562954
CMY: 102937044
CPIC: 101943409
ACS: 100565025
PVT: 110078231
PBI: 103054208
PMUR: 107292512
TSR: 106540772
PMUA: 114603027
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(si:dkey-91i10.3) 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 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
CEL: CELE_T13C5.1(daf-9)
CBR: CBG10440 CBG14860(Cbr-daf-9)
BMY: Bm1_42095
LOA: LOAG_03116
 » 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
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