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
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
CSEM: 103380225
LCF: 108886266
HCQ: 109519394
BPEC: 110163820
SASA: 106561846(P450scc)
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 (1975) 9028-37.
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 (1981) 4321-8.
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 (1986) 27-31.
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 (2011) 10139-43.
  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 (2011) 5607-13.
  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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