Entry
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
Orthology
K00498 cholesterol monooxygenase (side-chain-cleaving)
Genes
CPOC : 100716515 100721940
DSP : 122098454 122098455 122098456 122098457 122098458
DMER : 138841807 138841810(Cyp11a1)
TVP : 118828559 118829326 118829423
LSR : 110468679 110482567(CYP11A1)
XLA : 108712986(cyp11a1.S)
DRE : 563363(cyp11a1.2) 80374(cyp11a1.1)
CCAR : 109044858 109082245
CAUA : 113043547 113067058
CGIB : 127947488 128014634
CERY : 137014756(cyp11a1.2)
TROS : 130552087 130552089
CGOB : 115009784 115009785 115009786 115009787
PGEO : 117447987(cyp11a1.2)
CANA : 137803927(cyp11a1.2)
CVE : 137881117(cyp11a1.2)
SPUL : 138612769(cyp11a1.2)
ASTR : 137594363(cyp11a1.2)
EJA : 138206202(cyp11a1.2)
BFRE : 138626804(cyp11a1.2)
SSCV : 125970984(cyp11a1.2)
ENY : 140348868(cyp11a1.2)
ARUT : 117428538 117429302 117963031
BBEL : 109467542 109476488 109476522 109486367
» show all
Taxonomy
Reference
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
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
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
Reference
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
Sequence
Reference
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
Sequence
Other DBs
ExPASy - ENZYME nomenclature database: 1.14.15.6
CAS: 37292-81-2 440354-98-3