KEGG ENZYME: 1.14.15.6

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)

R02723 R02724 R03933 R04855;
(other) R01454 R04676 R04854

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:

GGO:

PON:

NLE:

MCC:

MCF:	102120640(CYP11A)

CSAB:

103245339(CYP11A1)

RRO:

104672245

RBB:

108531466

CJC:	100389930(CYP11A1)

SBQ:

101039906

MMU:	13070(Cyp11a1)

MCAL:

110301893

MPAH:

110328464

RNO:	29680(Cyp11a1)

MUN:	110554823 110554825

CGE:

NGI:

HGL:

CCAN:

OCU:	100345737(CYP11A1)

TUP:	102487565 102490722

CFA:	478365(CYP11A1)

VVP:

AML:

UMR:

UAH:

ORO:

FCA:

PTG:

AJU:

BTA:	338048(CYP11A1)

BOM:

BIU:

BBUB:

PHD:

CHX:	102173131(CYP11A1)

OAS:	100048994(CYP11A1)

SSC:	403329(CYP11A1)

CFR:

CDK:

BACU:

LVE:

OOR:

DLE:

PCAD:

ECB:	100034229(CYP11A1)

EPZ:

EAI:

MYB:

MYD:

MNA:

HAI:

RSS:

DRO:

PALE:

RAY:

LAV:

TMU:

MDO:

SHR:

PCW:

OAA:

GGA:	414838(CYP11A1)

MGP:

100543260

CJO:	107318663(P-450scc)

NMEL:

110403743

APLA:

101796693

ACYG:

106044184

TGU:	100151695(CYP11A1)

LSR:	110468679 110482567

GFR:

FAB:

PHI:

PMAJ:

CCAE:

ETL:

FPG:

FCH:

CLV:

EGZ:

NNI:

ACUN:

PADL:

AAM:

ASN:

AMJ:	102569028(CYP11A1)

PSS:

CMY:

CPIC:

PVT:

PBI:

PMUR:

GJA:

XLA:	108712986(cyp11a1.S)

XTR:	100495360(cyp11a1)

NPR:

108785561

DRE:	563363(cyp11a2) 80374(cyp11a1)

SRX:	107705097 107751280

SANH:

107703186

SGH:

107589342

CCAR:

109044858

IPU:	100313513(cyp11a)

PHYP:

AMEX:

EEE:

TRU:

TNG:	GSTEN00016006G001

LCO:

104924331

NCC:

104966693

MZE:

101471001

OLA:	100302421(cyp11a)

XMA:

XCO:

PRET:

NFU:

KMR:

AOCE:

CSEM:

POV:

LCF:

SDU:

HCQ:

BPEC:

MALB:

SASA:

106561846(P450scc)

OTW:

SALP:

ELS:

SFM:

PKI:

LCM:

CMK:	103172797 103188165

LGI:	LOTGIDRAFT_158678

» 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]