KEGG   ENZYME: 1.14.15.6
Entry
EC 1.14.15.6                Enzyme                                 
Name
cholesterol monooxygenase (side-chain-cleaving);
cholesterol desmolase;
cytochrome P-450scc;
C27-side chain cleavage enzyme;
cholesterol 20-22-desmolase;
cholesterol C20-22 desmolase;
cholesterol side-chain cleavage enzyme;
cholesterol side-chain-cleaving enzyme;
steroid 20-22 desmolase;
steroid 20-22-lyase;
CYP11A1 (gene name)
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
cholesterol,reduced-adrenodoxin:oxygen oxidoreductase (side-chain-cleaving)
Reaction(IUBMB)
cholesterol + 6 reduced adrenodoxin + 3 O2 + 6 H+ = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction) [RN:R02724];
(1a) cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O [RN:R02723];
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O [RN:R04855];
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 + 2 H+ = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O [RN:R03933]
Reaction(KEGG)
Substrate
cholesterol [CPD:C00187];
reduced adrenodoxin [CPD:C00662];
O2 [CPD:C00007];
H+ [CPD:C00080];
(22R)-22-hydroxycholesterol [CPD:C05502];
(20R,22R)-20,22-dihydroxy-cholesterol
Product
pregnenolone [CPD:C01953];
4-methylpentanal [CPD:C02373];
oxidized adrenodoxin [CPD:C00667];
H2O [CPD:C00001];
(22R)-22-hydroxycholesterol [CPD:C05502];
(20R,22R)-20,22-dihydroxycholesterol
Comment
A heme-thiolate protein (cytochrome P-450). The reaction proceeds in three stages, with two hydroxylations at C-22 and C-20 preceding scission of the side-chain between carbons 20 and 22. 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 1.14.15.6 created 1983, modified 2013, modified 2014
Pathway
ec00140  Steroid hormone biosynthesis
ec01100  Metabolic pathways
Orthology
K00498  cholesterol monooxygenase (side-chain-cleaving)
Genes
HSA1583(CYP11A1)
PTR748998(CYP11A1)
PPS100979902(CYP11A1)
GGO101124697
PON100433169
NLE100595981
MCC708065
MCF102120640(CYP11A1)
CSAB103245339(CYP11A1)
CATY105600069
PANU101026207
TGE112627656
RRO104672245
RBB108531466
TFN117070377
PTEH111529691
CJC100389930(CYP11A1)
SBQ101039906
CSYR103273593
MMUR105862155
OGA100951412
MMU13070(Cyp11a1)
MCAL110301893
MPAH110328464
RNO29680(Cyp11a1)
MCOC116073505
MUN110554823 110554825
CGE100752606
MAUA101827747
PLEU114690350
MORG121445604
NGI103736867
HGL101704598
CPOC100716515 100721940
CCAN109687652
DORD105982351
DSP122098454 122098455 122098456 122098457 122098458
NCAR124977503
OCU100345737(CYP11A1)
OPI101531464
TUP102487565
CFA478365(CYP11A1)
VVP112917406
VLG121485703
AML100474049
UMR103678997
UAH113240963
UAR123790690
ELK111153362
LLV125105609
MPUF101670840
ORO101384815
EJU114206275
ZCA113909555
MLX118003325
FCA101085980
PYU121041978
PBG122468436
PTG102964439
PPAD109262704
AJU106979451
HHV120235769
BTA338048(CYP11A1)
BOM102282116
BIU109575664
BBUB102400151
CHX102173131(CYP11A1)
OAS100048994(CYP11A1)
ODA120875441
CCAD122455135
SSC403329(CYP11A1)
CFR102516700
CBAI105069199
CDK105087270
VPC102526586
BACU103011342
LVE103068564
OOR101284598
DLE111177811
PCAD102978389
PSIU116749046
ECB100034229(CYP11A1)
EPZ103567309
EAI106842692
MYB102241006
MYD102765728
MMYO118675837
MLF102433032
MNA107535212
PKL118728890
HAI109396248
DRO112301926
SHON118987828
AJM119041324
PDIC114492772
PHAS123825290
MMF118641290
RFQ117022918
PALE102894190
PGIG120597907
PVP105306828
RAY107510545
MJV108390538
TOD119238427
SARA101550083
LAV100665050
TMU101357207
DNM101418002
MDO100029519
GAS123234348
SHR100923284
PCW110214023
OAA100076626 114814661
GGA414838(CYP11A1)
PCOC116244549
MGP100543260
CJO107318663
NMEL110403743
APLA101796693
ACYG106044184
AFUL116493636
TGU100151695(CYP11A1)
LSR110468679 110482567
PMOA120504845
OTC121343597
PRUF121365512
GFR102043993
FAB101810676
PHI102109180
PMAJ107209117
ETL114059742
FPG101916429
FCH102049639
CLV102096337
EGZ104130717
NNI104016802
ACUN113483867
TALA104361621
PADL103922056
ACHC115341287
AAM106487382
AROW112967327
NPD112951010
DNE112992459
ASN102381626
AMJ102569028(CYP11A1)
PSS102455057
CMY102939633
CPIC101950099
TST117884392
CABI116821105
MRV120372839
PVT110084450
SUND121934581
PBI103056955
PMUR107291917
TSR106553315
PGUT117659566
VKO123033771
PMUA114604069
ZVI118079191 118084488
GJA107111326
XLA108712986(cyp11a1.S)
XTR100495360(cyp11a1)
NPR108785561
RTEM120931500
BBUF120985643
BGAR122929707
DRE563363(cyp11a2) 80374(cyp11a1)
SRX107751280
SANH107703186
SGH107589342
CCAR109044858
CAUA113043547 113067058
PPRM120495594
MAMB125247683
IPU100313513(cyp11a)
PHYP113530122
SMEO124392299
TFD113659881
AMEX103021835
EEE113573160
TRU101063139
TNGGSTEN00016006G001
LCO104924331
NCC104966693
CGOB115009784 115009785 115009786 115009787
ELY117262855
PLEP121949937
SLUC116038300
ECRA117949155
PFLV114560394
GAT120808883
PPUG119196509
MSAM119894014
CUD121514436
ALAT119023908
MZE101471001
ONL100692956
OAU116326291
OLA100302421(cyp11a)
OML112152747
XMA102235384
XCO114151402
XHE116729990
PRET103466560
PFOR103141253
PLAI106959477
PMEI106927170
GAF122835039
CVG107101674
CTUL119772345
GMU124860809
NFU107388733
KMR108229950
ALIM106514397
NWH119416479
AOCE111587899
CSEM103380225
POV109624184
SSEN122775933
HHIP117763592
HSP118109743
LCF108886266
SDU111228419
SLAL111666903
XGL120793299
HCQ109519394
BPEC110163820
MALB109971254
BSPL114856786
SASA106561846(P450scc)
OTW112218957
OMY110501505
OGO124031492
ONE115125603
SALP112071531
SNH120042159
ELS105007422
SFM108926637
PKI111846669
AANG118215491
LOC102686734
PSPA121298788
ARUT117428538 117429302 117963031
LCM102360223
CMK103188165
BBEL109467542 109476488 109476522 109486367
AGB108915653
APLN108738345
PJA122262122
 » show all
Reference
1  [PMID:1238395]
  Authors
Burstein S, Middleditch BS, Gut M
  Title
Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22-dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the lgycol and pregnenolone in bovine adrenocortical preparations. Mode of oxygen incorporation.
  Journal
J Biol Chem 250:9028-37 (1975)
Reference
2  [PMID:7217084]
  Authors
Hanukoglu I, Spitsberg V, Bumpus JA, Dus KM, Jefcoate CR.
  Title
Adrenal mitochondrial cytochrome P-450scc. Cholesterol and adrenodoxin interactions at equilibrium and during turnover.
  Journal
J Biol Chem 256:4321-8 (1981)
Reference
3  [PMID:3011431]
  Authors
Hanukoglu I, Hanukoglu Z
  Title
Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation.
  Journal
Eur J Biochem 157:27-31 (1986)
DOI:10.1111/j.1432-1033.1986.tb09633.x
Reference
4  [PMID:21636783]
  Authors
Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW
  Title
Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.
  Journal
Proc Natl Acad Sci U S A 108:10139-43 (2011)
DOI:10.1073/pnas.1019441108
  Sequence
[hsa:1583]
Reference
5  [PMID:21159775]
  Authors
Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA
  Title
Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1.
  Journal
J Biol Chem 286:5607-13 (2011)
DOI:10.1074/jbc.M110.188433
  Sequence
[bta:338048]
Other DBs
ExplorEnz - The Enzyme Database: 1.14.15.6
IUBMB Enzyme Nomenclature: 1.14.15.6
ExPASy - ENZYME nomenclature database: 1.14.15.6
BRENDA, the Enzyme Database: 1.14.15.6
CAS: 37292-81-2 440354-98-3
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