KEGG   ENZYME: 1.14.15.6Help
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
BRITE hierarchy
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
HSA: 1583(CYP11A1)
PTR: 748998(CYP11A1)
PPS: 100979902
GGO: 101124697
PON: 100433169
NLE: 100595981
MCC: 708065(CYP11A1)
MCF: 102120640(CYP11A)
CSAB: 103245339(CYP11A1)
RRO: 104672245
RBB: 108531466
CJC: 100389930(CYP11A1)
SBQ: 101039906
MMU: 13070(Cyp11a1)
RNO: 29680(Cyp11a1)
CGE: 100752606
NGI: 103736867
HGL: 101704598
CCAN: 109687652
OCU: 100345737(CYP11A1)
CFA: 478365(CYP11A1)
AML: 100474049
UMR: 103678997
ORO: 101384815
FCA: 101085980
PTG: 102964439
AJU: 106979451
BTA: 338048(CYP11A1)
BOM: 102282116
BIU: 109575664
PHD: 102317428
CHX: 102173131(CYP11A1)
OAS: 100048994(CYP11A1)
SSC: 403329(CYP11A1)
CFR: 102516700
CDK: 105087270
BACU: 103011342
LVE: 103068564
OOR: 101284598
ECB: 100034229(CYP11A1)
EPZ: 103567309
EAI: 106842692
MYB: 102241006
MYD: 102765728
HAI: 109396248
RSS: 109449550
PALE: 102894190
LAV: 100665050
TMU: 101357207
MDO: 100029519
SHR: 100923284
OAA: 100076626
GGA: 414838(CYP11A1)
MGP: 100543260
CJO: 107318663(P-450scc)
APLA: 101796693
ACYG: 106044184
TGU: 100151695(CYP11A1)
GFR: 102043993
FAB: 101810676
PHI: 102109180
PMAJ: 107209117
CCAE: 111944465
FPG: 101916429
FCH: 102049639
CLV: 102096337
EGZ: 104130717
AAM: 106487382
ASN: 102381626
AMJ: 102569028(CYP11A1)
PSS: 102455057
CMY: 102939633
CPIC: 101950099
PVT: 110084450
PBI: 103056955
GJA: 107111326
XLA: 108712986(cyp11a1.S)
XTR: 100495360(cyp11a1)
NPR: 108785561
DRE: 563363(cyp11a2) 80374(cyp11a1)
SANH: 107703186
SGH: 107589342
CCAR: 109044858
IPU: 100313513(cyp11a)
AMEX: 103021835
TRU: 101063139
LCO: 104924331
NCC: 104966693
MZE: 101471001
OLA: 100302421(cyp11a)
XMA: 102235384
PRET: 103466560
NFU: 107388733
KMR: 108229950
CSEM: 103380225
LCF: 108886266
SDU: 111228419
HCQ: 109519394
BPEC: 110163820
MALB: 109971254
SASA: 106561846(P450scc)
OTW: 112218957
ELS: 105007422
SFM: 108926637
LCM: 102360223
 » show all
Taxonomy
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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