KEGG ENZYME: 1.14.15.16

ENZYME: 1.14.15.16

Entry

EC 1.14.15.16               Enzyme

Name

vitamin D3 24-hydroxylase;
CYP24A1

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

calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)

Reaction(IUBMB)

(1) calcitriol + 2 reduced adrenodoxin + 2 H+ + O2 = calcitetrol + 2 oxidized adrenodoxin + H2O [RN:R09515];
(2) calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 = secalciferol + 2 oxidized adrenodoxin + H2O [RN:R09516]

Reaction(KEGG)

R09515 R09516

Substrate

calcitriol [CPD:C01673];
reduced adrenodoxin [CPD:C00662];
H+ [CPD:C00080];
O2 [CPD:C00007];
calcidiol [CPD:C01561]

Product

calcitetrol [CPD:C18231];
oxidized adrenodoxin [CPD:C00667];
H2O [CPD:C00001];
secalciferol [CPD:C07712]

Comment

This mitochondrial cytochrome P-450 enzyme requires adrenodoxin. The enzyme can perform up to 6 rounds of hydroxylation of the substrate calcitriol leading to calcitroic acid. The human enzyme also shows 23-hydroxylating activity leading to 1,25 dihydroxyvitamin D3-26,23-lactone as end product while the mouse and rat enzymes do not. 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 1.14.15.16 created 2011 as EC 1.14.13.126, transferred 2016 to EC 1.14.15.16

Pathway

ec00100

Steroid biosynthesis

ec01100

Metabolic pathways

Orthology

K07436

vitamin D3 24-hydroxylase

Genes

HSA:	1591(CYP24A1)

PTR:	746729(CYP24A1)

PPS:	100971976(CYP24A1)

GGO:

101142284

PON:

100457433

NLE:

100603459

HMH:

116461006

MCC:

698937

MCF:	102117231(CYP24A1)

MTHB:

126929847

MNI:

105470644

CSAB:

103243965(CYP24A1)

CATY:

105585362

PANU:

100997369

TGE:

112632353

MLEU:

105538302

RRO:

104662355

RBB:

108521781

TFN:

117068948

PTEH:

111521023

CANG:

105507983

CJC:

100393283

SBQ:

101054511

CIMI:

108281352(CYP24A1)

CSYR:

103265086

MMUR:

105864362 105869419

LCAT:

123622312

PCOQ:

105811599

OGA:

100948814

MMU:	13081(Cyp24a1)

MCAL:

110289544

MPAH:

110318266

RNO:	25279(Cyp24a1)

MCOC:

116091462

ANU:

117703542

MUN:

110545262

CGE:

100751280

MAUA:

101827330

PROB:

127225192

PLEU:

114704035

MORG:

121440893

MFOT:

126508008

AAMP:

119815492

NGI:

103735781

HGL:

101716773

CPOC:

100728021

CCAN:

109694681

DORD:

105991653

DSP:

122124591

PLOP:

125353900

NCAR:

124978047

MMMA:

107137340

OCU:

100347441

OPI:

101526808

TUP:

102471055

GVR:

103588022

CFA:	485935(CYP24A1)

CLUD:

112674140

VVP:

112931920

VLG:

121477768

NPO:

129495117

AML:

100479790

UMR:

103669826

UAH:

113258741

UAR:

123799375

ELK:

111141789

LLV:

125109083

MPUF:

101678691

MNP:

132022040

MLK:

131807947

NVS:

122915540

ORO:

101384402

EJU:

114225492

ZCA:

113938600

MLX:

118024098

NSU:

110569858

LWW:

102751252

FCA:	101096141(CYP24A1)

PYU:

121019910

PCOO:

112869096

PBG:

122467253

PVIV:

125162613

LRUF:

124504391

PTG:

102967619

PPAD:

109272242

PUC:

125936486

AJU:

106970319

HHV:

120230459

BTA:	540080(CYP24A1)

BOM:

102272075

BIU:

109567562

BBUB:

102396198

BBIS:

104988843

CHX:

102178921

OAS:	100170323(CYP24)

BTAX:

128058745

ODA:

120869048

CCAD:

122448475

MBEZ:

129556173

SSC:	397145(CYP24A1)

CFR:

102516204

CBAI:

105071834

CDK:

105098859

VPC:

102531787

BACU:

103015403

BMUS:

118881970

LVE:

103082411

OOR:

101271151

DLE:

111186695

PCAD:

102977275

PSIU:

116740225

NASI:

112403033

ECB:	100053452(CYP24A1)

EPZ:

103554239

EAI:

106825434

MYB:

102249295

MYD:

102772049

MMYO:

118663454

MLF:

102432347

PKL:

118708044

EFUS:

103285757

MNA:

107536509

DRO:

112304205

SHON:

118996516

AJM:

119040651

PDIC:

114506963

PHAS:

123815183

MMF:

118619039

PPAM:

129070417

HAI:

109381840

RFQ:

117015976

PALE:

102878689

PGIG:

120603843

PVP:

105296033

RAY:

107498143

MJV:

108390269

TOD:

119254587

SARA:

101543781

LAV:

100663262

TMU:

101353460

ETF:

101646845

DNM:

101442213

MDO:

100028177

GAS:

123233554

SHR:

100916072

AFZ:

127548933

PCW:

110206681

OAA:

100078505

GGA:	395827(CYP24A1)

PCOC:

116227703

MGP:

100541378

CJO:

107323241

TPAI:

128080918

LMUT:

125701250

NMEL:

110408247

APLA:

101797037

ACYG:

106041795

CATA:

118248976

AFUL:

116495811

TGU:

100226727

LSR:

110472394

SCAN:

103818886

PMOA:

120507065

OTC:

121342986

PRUF:

121359459

GFR:

102044237

FAB:

101813067

OMA:

130261171

PHI:

102111029

PMAJ:

107213207

CCAE:

111938004

CCW:

104687601

CBRC:

103616823

ETL:

114056255

ZAB:

102067744

ACHL:

103801335

SVG:

106853090

MMEA:

130582173

HRT:

120760156

FPG:

101919538

FCH:

102046853

CLV:

102098516

EGZ:

104132191

NNI:

104013059

PCRI:

104024392

PLET:

104624707

EHS:

104503318

PCAO:

104039545

ACUN:

113487633

TALA:

104355745

PADL:

103919278

AFOR:

103894637

ACHC:

115339853

HALD:

104317033

HLE:

104833207

AGEN:

126045322

GCL:

127023359

CCRI:

104163872

CSTI:

104559611

CMAC:

104483098

MUI:

104537354

BREG:

104629802

FGA:

104069789

GSTE:

104258977

LDI:

104340282

MNB:

103775032

OHA:

104328853

NNT:

104412533

SHAB:

115615252

DPUB:

104302691

PGUU:

104464606

ACAR:

104526380

CPEA:

104389628

AVIT:

104274781

CVF:

104293941

RTD:

128916821

CUCA:

104057394

TEO:

104375190

BRHI:

104499916

AAM:

106491745

AROW:

112960579

NPD:

112949674

TGT:

104576182

DNE:

112982887

SCAM:

104150031

ASN:

102382614

AMJ:	102574966(CYP24A1)

CPOO:

109318764

GGN:

109292377

PSS:

102458142

CMY:

102932138

CCAY:

125622449

DCC:

119842129

CPIC:

101938071

TST:

117886274

CABI:

116821477

MRV:

120379784

ACS:	100555767 100564552

ASAO:

132773120

PVT:

110071817

SUND:

121927742

PBI:

103065707

PMUR:

107287085

CTIG:

120308207

TSR:

106547483

PGUT:

117674844

APRI:

131195709

PTEX:

113434347

NSS:

113410403

VKO:

123036291

PMUA:

114599654

PRAF:

128416477

ZVI:

118089322

HCG:

128353023

GJA:

107119104

STOW:

125432416

EMC:

129330710

XLA:	108700906(cyp24a1.L) 108718538

XTR:	100496967 100497429(cyp24a1)

NPR:	108784249 108790437

RTEM:

120940805

BBUF:

121001334

BGAR:

122939129

MUO:

115456829

GSH:

117356032

DRE:	100004700(cyp24a1)

SRX:

107744352

SANH:

107666154 107696435

SGH:	107560513 107587600

CCAR:

109057669

CAUA:

113050135 113078343 113104946 113105072

CGIB:

127959124 128016032

PTET:

122347370

LROH:

127167146

OMC:

131543101

PPRM:

120493676

RKG:

130104145

MAMB:

125273354

CIDE:

127514698

MASI:

127446014 127449569

TROS:

130556927

TDW:

130425264

MANU:

129451013

IPU:

108271496

IFU:

128615088

PHYP:

113532087

SMEO:

124388872

TFD:

113642663

TVC:

132844614

AMEX:

103030576

CMAO:

118808505

EEE:

113571660

CHAR:

105907715

TRU:

101077963

TFS:

130524793

TNG:	GSTEN00033861G001

LCO:

104935382

NCC:

104966082

TBEN:

117489819

CGOB:

115008593

PGEO:

117447336

GACU:

117539590

EMAC:

134883524

ELY:

117257164

EFO:

125895063

PLEP:

121959102

SLUC:

116051531

ECRA:

117943678

ESP:

116687595

PFLV:

114554700

GAT:

120835793

PPUG:

119194098

AFB:

129105552

CLUM:

117731186

PSWI:

130209058

MSAM:

119885885

SCHU:

122884848

CUD:

121507546

ALAT:

119020664

MZE:

101475325

ONL:

100690876

OAU:

116319460

OLA:

101165632

OML:

112145619

CSAI:

133449287

XMA:

102225814

XCO:

114135962

XHE:

116711044

PRET:

103464673

PFOR:

103134567

PLAI:

106960246

PMEI:

106929021

GAF:

122833415

PPRL:

129372875

CVG:

107097105

CTUL:

119788661

GMU:

124856320

NFU:

107385407

KMR:

108231477

ALIM:

106533681

NWH:

119411875

AOCE:

111579624

MCEP:

125006146

CSEM:

103386736

POV:

109635373

SSEN:

122767772

HHIP:

117761120

HSP:

118103196

SMAU:

118310037

LCF:

108873562

SDU:

111233601

SLAL:

111660685

XGL:

120783454

HCQ:

109507475

SSCV:

125977385

SBIA:

133507962

PEE:

133408898

PTAO:

133483835

BPEC:

110171174

MALB:

109951265

BSPL:

114856188

SJO:

128355486

SASA:

106565076(CP24A) 106583685

STRU:

115150083 115208378

OTW:	112255537 112267058

OMY:	100136661 110493887

OGO:	124002353 124018524

ONE:	115125232 115142853

OKI:	109890306 109891209

OKE:	118373224 118388929

SALP:

111961723 111970527

SNH:	120064455 120065468

CCLU:

121575591 121577964

ELS:

105016677

SFM:

108936451

PKI:

111835893

AANG:

118210803

LOC:

102698913

PSPA:

121297804 121319232

ARUT:

117418538 117433450

PSEX:

120515040

LCM:

102364004

CMK:

103191047

RTP:

109910917

CPLA:

122560047

HOC:

132822650

LERI:

129707428

PMRN:

116952143

LRJ:

133354894

ACOO:

126841906

DVT:

126895652

HVI:

124356704

MQU:

129004834

HAME:

121870079

CQD:

128687363

RSAN:

119392951

RMP:

119172898

PMEO:

129595599

GAE:	121366250 121373112

HRF:	124134044 124135907

HRJ:	124282302 124283687 124289154

CANU:

128183315

OED:

125677184

HSY:

130622697

» show all

Reference

1 [PMID:16516540]

Authors

Masuda S, Strugnell SA, Knutson JC, St-Arnaud R, Jones G

Title

Evidence for the activation of 1alpha-hydroxyvitamin D2 by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1alpha,24-dihydroxyvitamin D2 and 1alpha,25-dihydroxyvitamin D2.

Journal

Biochim Biophys Acta 1761:221-34 (2006)
DOI:10.1016/j.bbalip.2006.01.004

Reference

2 [PMID:16617161]

Authors

Hamamoto H, Kusudo T, Urushino N, Masuno H, Yamamoto K, Yamada S, Kamakura M, Ohta M, Inouye K, Sakaki T

Title

Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats.

Journal

Mol Pharmacol 70:120-8 (2006)
DOI:10.1124/mol.106.023275

Sequence

[rno:25279]

Reference

3 [PMID:15574355]

Authors

Sakaki T, Kagawa N, Yamamoto K, Inouye K

Title

Metabolism of vitamin D3 by cytochromes P450.

Journal

Front Biosci 10:119-34 (2005)
DOI:10.2741/1514

Sequence

[hsa:1591]

Reference

4 [PMID:17646648]

Authors

Prosser DE, Kaufmann M, O'Leary B, Byford V, Jones G

Title

Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1alpha,25-(OH)2D3-26,23-lactone.

Journal

Proc Natl Acad Sci U S A 104:12673-8 (2007)
DOI:10.1073/pnas.0702093104

Reference

5 [PMID:15358094]

Authors

Kusudo T, Sakaki T, Abe D, Fujishima T, Kittaka A, Takayama H, Hatakeyama S, Ohta M, Inouye K

Title

Metabolism of A-ring diastereomers of 1alpha,25-dihydroxyvitamin D3 by CYP24A1.

Journal

Biochem Biophys Res Commun 321:774-82 (2004)
DOI:10.1016/j.bbrc.2004.07.040

Reference

6 [PMID:15078099]

Authors

Sawada N, Kusudo T, Sakaki T, Hatakeyama S, Hanada M, Abe D, Kamao M, Okano T, Ohta M, Inouye K

Title

Novel metabolism of 1 alpha,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1.

Journal

Biochemistry 43:4530-7 (2004)
DOI:10.1021/bi030207f

Reference

7 [PMID:15544953]

Authors

Prosser DE, Jones G

Title

Enzymes involved in the activation and inactivation of vitamin D.

Journal

Trends Biochem Sci 29:664-73 (2004)
DOI:10.1016/j.tibs.2004.10.005

Other DBs

ExplorEnz - The Enzyme Database:

1.14.15.16

IUBMB Enzyme Nomenclature:

1.14.15.16

ExPASy - ENZYME nomenclature database:

1.14.15.16

BRENDA, the Enzyme Database:

1.14.15.16

DBGET integrated database retrieval system