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 = pregnenolone + 4-methylpentanal + 6 oxidized adrenodoxin + 4 H2O (overall reaction) [RN:R02724];
(1a) cholesterol + 2 reduced adrenodoxin + O2 = (22R)-22-hydroxycholesterol + 2 oxidized adrenodoxin + H2O;
(1b) (22R)-22-hydroxycholesterol + 2 reduced adrenodoxin + O2 = (20R,22R)-20,22-dihydroxycholesterol + 2 oxidized adrenodoxin + H2O;
(1c) (20R,22R)-20,22-dihydroxy-cholesterol + 2 reduced adrenodoxin + O2 = pregnenolone + 4-methylpentanal + 2 oxidized adrenodoxin + 2 H2O
Reaction(KEGG)
Substrate
cholesterol [CPD:C00187];
reduced adrenodoxin [CPD:C00662];
O2 [CPD:C00007];
(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
Pathway
Steroid hormone biosynthesis
Metabolic pathways
Orthology
K00498  
cholesterol monooxygenase (side-chain-cleaving)
Genes
HSA: 
1583(CYP11A1)
PTR: 
748998(CYP11A1)
PPS: 
GGO: 
PON: 
MCC: 
MCF: 
102120640(CYP11A)
MMU: 
13070(Cyp11a1)
RNO: 
29680(Cyp11a1)
HGL: 
TUP: 
CFA: 
478365(CYP11A1)
AML: 
FCA: 
PTG: 
BTA: 
338048(CYP11A1)
BOM: 
PHD: 
CHX: 
102173131(CYP11A1)
SSC: 
403329(CYP11A1)
CFR: 
ECB: 
100034229(CYP11A1)
MYB: 
MYD: 
PALE: 
MDO: 
SHR: 
GGA: 
414838(CYP11A1)
TGU: 
100151695(CYP11A1)
FAB: 
PHI: 
APLA: 
FPG: 
FCH: 
CLV: 
ASN: 
PSS: 
CMY: 
XTR: 
DRE: 
563363 80374(cyp11a1)
TRU: 
MZE: 
OLA: 
100302421(cyp11a)
XMA: 
LCM: 
 » 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.
  Organism
Bos taurus
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.
  Organism
Bos taurus
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.
  Organism
Bos taurus
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.
  Organism
Homo sapiens
  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.
  Organism
Bos taurus
  Sequence
[bta:338048]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
37292-81-2 440354-98-3

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