KEGG ENZYME: 1.14.14.25

ENZYME: 1.14.14.25

Entry

EC 1.14.14.25               Enzyme

Name

cholesterol 24-hydroxylase;
cholesterol 24-monooxygenase;
CYP46;
CYP46A1;
cholesterol 24S-hydroxylase;
cytochrome P450 46A1

Class

Oxidoreductases;
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor

Sysname

cholesterol,NADPH---hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)

Reaction(IUBMB)

cholesterol + [reduced NADPH---hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R07207]

Reaction(KEGG)

R07207

Substrate

cholesterol [CPD:C00187];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007]

Product

(24S)-cholest-5-ene-3beta,24-diol [CPD:C13550];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001]

Comment

A P-450 heme-thiolate protein. The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood---brain barrier whereas cholesterol cannot [3]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase [3].

History

EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25

Pathway

ec00120

Primary bile acid biosynthesis

Orthology

K07440

cholesterol 24-hydroxylase

Genes

HSA:	10858(CYP46A1)

PTR:	453154(CYP46A1)

PPS:	100978372(CYP46A1)

GGO:

101142101

PON:

100440873

PPYG:

129012883

NLE:

100604931

HMH:

116484938

SSYN:

129487455

MCC:

705843

MCF:	102140307(CYP46A1)

MTHB:

126958426

MNI:

105467428

CSAB:

103229682(CYP46A1)

CATY:

105596681

PANU:

101024697

TGE:

112628803

MLEU:

105547886

RRO:

104654463

RBB:

108519071

TFN:

117071399

PTEH:

111538292

CANG:

105518476

CJC:	100403833(CYP46A1)

SBQ:

101048333

CIMI:

108304092(CYP46A1)

ANAN:

105730202(CYP46A1)

CSYR:

103252598

MMUR:

105861542

LCAT:

123640115

PCOQ:

105814966

OGA:

100967073

MMU:	13116(Cyp46a1)

MCAL:

110306885

MPAH:

110324576

RNO:	362782(Cyp46a1)

MCOC:

116081177

ANU:

117697515

MUN:

110566352

CGE:

100769865

MAUA:

101835570

PROB:

127231129

PLEU:

114701904

MORG:

121434402

MFOT:

126509127

AAMP:

119819628

NGI:

103727655

HGL:

101708822

CPOC:

100729775

CCAN:

109694347

DORD:

105984431

DSP:

122118796

PLOP:

125363049

NCAR:

124977121

MMMA:

107150458

OCU:

100354574

OPI:

101521226

TUP:

102499401

GVR:

103596306

CFA:	480432(CYP46A1)

CLUD:

112657091

VVP:

112930232

VLG:

121492487

NPO:

129496138

AML:

100470338

UMR:

103673592

UAH:

113267281

UAR:

123778173

ELK:

111148659

LLV:

125105074

MPUF:

101688078

MNP:

131998924

MLK:

131836979

NVS:

122893909

ORO:

101365372

EJU:

114207104

ZCA:

113909603

MLX:

118002291

NSU:

110571558

LWW:

102731939

FCA:	101093112(CYP46A1)

PYU:

121032271

PCOO:

112855884

PBG:

122469524

PVIV:

125168283

LRUF:

124512078

PTG:

102970492

PPAD:

109274544

PUC:	125917830 125917833

AJU:

106972183

HHV:

120245736

BTA:	506438(CYP46A1)

BOM:

102270768

BBUB:

102397524

BBIS:

104997009

CHX:

102178217

OAS:

101117622

BTAX:

128066926

ODA:

120875206

CCAD:

122419692

MBEZ:

129550174

SSC:

100512793

CFR:

102522998

CBAI:

105079921

CDK:

105095410

VPC:

102525462

BACU:

103014370

BMUS:

118889537

LVE:

103068707

OOR:

101280175

DLE:

111176091

PCAD:

102976598

PSIU:

116749111

NASI:

112409398

ECB:

100051131

EPZ:

103550566

EAI:

106839686

MYB:

102251844

MYD:

102761609

MMYO:

118660179

MLF:

102442827

MDT:

132229663

PKL:

118704261

EFUS:

103298044

MNA:

107542730

DRO:

112311755

SHON:

118976840

AJM:

119037986

PDIC:

114492701

PHAS:

123808339

MMF:

118635840

PPAM:

129066158

HAI:

109381070

RFQ:

117023672

PALE:

102898643

PGIG:

120619686

PVP:

105302289

RAY:

107518577

MJV:

108394816

TOD:

119238338

SARA:

101559384

SETR:

126003561

LAV:

100677635

TMU:

101353740

ETF:

101663884

DNM:

101426001

SHR:

100926883

AFZ:

127549918

PCW:

110222404

TVP:

118844835

OAA:

100082015

GGA:	423450(CYP46A1)

PCOC:

116228856

MGP:

100546708

CJO:

107315364

TPAI:

128085654

LMUT:

125695053

NMEL:

110401402

APLA:

101792317

ACYG:

106036083(CYP46A1)

CATA:

118258199

AFUL:

116489988

TGU:

100221970

LSR:

110481165

SCAN:

103826433

PMOA:

120503858

OTC:

121334142

PRUF:

121358280

GFR:

102044337

FAB:

101816121

OMA:

130253789

PHI:

102099615

PMAJ:

107206481

CCAE:

111929830

CCW:

104686436

CBRC:

103612232

ETL:

114061692

ZAB:

102075066

ZLE:

135448182

ACHL:

103810129

SVG:

106850564

MMEA:

130580262

HRT:

120754471

SATI:

136362912(CYP46A1)

FPG:

101918324

FCH:

102060075

CCRI:

104156050

NNT:

104400520

SHAB:

115607219

ACUN:

113480441

TALA:

104363360

ACHC:

115352583

HALD:

104311467

HLE:

104841975

AGEN:

126050700

GCL:

127017243

LDI:

104345231

MNB:

103770689

DPUB:

104304461

AVIT:

104268564

BRHI:

104496260

EGZ:

104124527

NNI:

104014834

PCRI:

104031368

PCAO:

104040180

PADL:

103920698

AFOR:

103900313

FGA:

104075935

GSTE:

104264892

CLV:

102086481

MUI:

104536998

PGUU:

104459206

PLET:

104626282

EHS:

104509622

CMAC:

104482699

CUCA:

104057794

TEO:

104382368

BREG:

104641150

OHA:

104331565

ACAR:

104529127

CPEA:

104389078

CVF:

104291789

RTD:

128909490

AAM:

106482958

AROW:

112972680

NPD:

112956935

TGT:

104568993

DNE:

112989932

SCAM:

104144448

ASN:

102376314

AMJ:	102574122(CYP46A1)

CPOO:

109321748

GGN:

109298462

PSS:

102449598

CMY:

102937516

CCAY:

125639047

DCC:

119858031

CPIC:

101950833

TST:

117876150

CABI:

116821838

MRV:

120402810

ACS:	100552409 100552607

ASAO:

132761810 132762545

PVT:	110089659 110089661

SUND:

121919235 121919747

PBI:

103060230

PMUR:

107291347

CTIG:

120306446

TSR:

106554955

PGUT:

117665976

APRI:

131187907

PTEX:

113434994

NSS:

113420326

VKO:	123018897 123032045

PMUA:

114585569 114585577 114588390

PRAF:

128407201 128407211 128407225

ZVI:	118080655 118080672

HCG:	128336795 128336801

GJA:	107121530 107121531

STOW:

125427125

EMC:	129324065 129324066 129324802 129324893 129324895 129324896 129324924

XLA:	100126648(cyp46a1.3.L) 108704878(cyp46a1.1.L) 379470(cyp46a1.2.L)

XTR:	100145328 100498621 613109(cyp46a1.3) 613111(cyp46a1.1) 780005(cyp46a1.2)

NPR:	108790745 108795063 108795064 108795072

RTEM:

120920042 120920174 120920768 120920898

BBUF:

120982153 120982331 120982402 120982403 120982405 120982407 120982408 120982409 120982490

BGAR:

122921922 122921989 122922124 122922206

MUO:

115478032

GSH:	117363605 117363915

DRE:	393433(cyp46a1.2) 393451(cyp46a1.4) 553543(cyp46a1.1) 641477(cyp46a1.5) 692332(cyp46a1.3)

SRX:	107728353 107747947

SANH:

107678664 107678670 107679679

SGH:	107555298 107572123

CCAR:

109113289 109113290

CAUA:

113121257 113121258

CGIB:

127983802

PTET:

122324318 122324319 122324561 122325035

LROH:

127183027

OMC:	131526937 131527697

PPRM:

120481378

RKG:

130096210

MAMB:

125277801

CIDE:

127502616

CERY:

137019317

MASI:

127410433 127415828

TROS:

130565740 130566380

TDW:	130434024 130434519 130434833

AMEX:

103039880

CMAO:

118800336

EEE:	113571915 113586723

CHAR:

105889656 105901399 105910686

TRU:	101061882 101077010

TFS:	130515942 130515943

LCO:

104926956

NCC:

104967646

TBEN:

117498568

CGOB:

115003685

PGEO:

117439935

GACU:

117554294

EMAC:

134876615

ELY:	117270337 117270909

EFO:	125897078 125897080

PLEP:

121955336 121955367

SLUC:

116041942 116041943 116041944

ECRA:

117961088

ESP:

116706702

PFLV:

114573150 114573151 114573152 114573153

GAT:

120808146

PPUG:

119195418

AFB:

129106877

CLUM:

117727841

PSWI:

130202737

MSAM:

119908603 119908604

SCHU:

122863503 122863505

CUD:	121510023 121521266 121521471

ALAT:

119013059

MZE:	101466901 101484290 101484552 106676579 111500322

ONL:	100692681 100703511 100704054 102076821 102077122

OAU:	116315530 116315535 116315536 116332193 116332210 120433299

OLA:	101165021 101165274

OML:	112157723 112157725

CSAI:

133464385 133464386 133464538

XMA:	102224087 106699939

XCO:	114158714 114158715

XHE:	116734217 116734218

PRET:

103457823 103457824

PFOR:

103147687 103147688

PLAI:

106956892 106956894

PMEI:

106916229 106916230

GAF:	122825489 122825709

PPRL:

129368916 129368917

CVG:	107097647 107097654

CTUL:

119784179 119784180 119784181

GMU:	124882165 124882166 124882576

NFU:	107378149 107378150

KMR:	108231774 108231837 108231838 112450290

ALIM:

106525137 106525457 106525458

NWH:	119418059 119418455 119418456 119418457 119418458

AOCE:

111578258

MCEP:

124998779

CSEM:

103380705

POV:

109632307

SSEN:

122783686

HHIP:

117758428

HSP:

118099372

PPLT:

128460280

SMAU:

118290645

LCF:

108898059

SDU:

111240402

SLAL:

111672518

XGL:

120788907

HCQ:

109523501

SSCV:

125990426

SBIA:

133496274

PEE:

133416871

PTAO:

133468237

BPEC:

110161286 110173902 110173912

MALB:

109962169 109962173 109962186 109962187

BSPL:

114849186 114849188

SJO:	128377315 128377316 128377317 128377319

SASA:

106571109 106571110 106571111 106608238

STRU:

115157569 115175113 115175114 115175200

OTW:	112235780 112249824 112249887 112249888

OMY:	110522567 110529322 110529323 110529324 110529326 118965490

OGO:	123990517 123995395

ONE:	115107524 115122868

OKI:	109866694 109900502 109900504 109900505 109901317 109901319

OKE:

118371881

SALP:

111954047 111972528

SNH:	120019174 120024159 120024160

CCLU:

121548510 121552816 121552818

ELS:	105020476 105020477 105020478 106024908 109614563

SFM:	114910933 114912327 114912328 114912329

PKI:

111850949

AANG:

118230143 118230144 118230145 118230146 118230147

LOC:

102686415

PSPA:

121324127

ARUT:

117420692 117422588

PSEX:

120518902

LCM:

102350084

CMK:

103191174

CPLA:

122553321

HOC:	132818016 132818018

BFO:

118426351

BBEL:

109461803

SPU:

575475

LPIC:

129260635 129261079 129265168 129265494 129269742 129270038 129270403 129279633

ARUN:

117287882 117288430 117289895 117295713 117295909 117298510 117300170 117300325 117300896 117304390 117304391 117304585 117306872 117306975

MYI:

110442672

PMAX:

117323274 117323275 117323276 117323277 117323279 117323755 117324632 117327808

MCAF:

127698395 127698497

LJP:

135471645

LLON:

135485055 135500571

ATEN:

116288258 116291041 116301076 116301543 116301544 116302235

XEN:	124434130 124434667 124434668 124434669 124434670 124434671 124435711 124445703

RES:

135688545

» show all

Reference

1 [PMID:10377398]

Authors

Lund EG, Guileyardo JM, Russell DW

Title

cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain.

Journal

Proc Natl Acad Sci U S A 96:7238-43 (1999)
DOI:10.1073/pnas.96.13.7238

Sequence

[hsa:10858] [mmu:13116]

Reference

2 [PMID:11698143]

Authors

Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, Russell DW, Bjorkhem I.

Title

On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells.

Journal

Neurosci Lett 314:45-8 (2001)
DOI:10.1016/S0304-3940(01)02277-7

Sequence

[hsa:10858]

Reference

3 [PMID:14640697]

Authors

Mast N, Norcross R, Andersson U, Shou M, Nakayama K, Bjorkhem I, Pikuleva IA

Title

Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.

Journal

Biochemistry 42:14284-92 (2003)
DOI:10.1021/bi035512f

Sequence

[hsa:10858]

Reference

4 [PMID:12686551]

Authors

Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW.

Title

Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover.

Journal

J Biol Chem 278:22980-8 (2003)
DOI:10.1074/jbc.M303415200

Reference

5 [PMID:12543708]

Authors

Russell DW

Title

The enzymes, regulation, and genetics of bile acid synthesis.

Journal

Annu Rev Biochem 72:137-74 (2003)
DOI:10.1146/annurev.biochem.72.121801.161712

Other DBs

ExplorEnz - The Enzyme Database:

1.14.14.25

IUBMB Enzyme Nomenclature:

1.14.14.25

ExPASy - ENZYME nomenclature database:

1.14.14.25

BRENDA, the Enzyme Database:

1.14.14.25

CAS:	50812-30-1 213327-78-7

LinkDB

DBGET integrated database retrieval system