KEGG   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
HSA1591(CYP24A1)
PTR746729(CYP24A1)
PPS100971976(CYP24A1)
GGO101142284
PON100457433
PPYG129021736
NLE100603459
HMH116461006
SSYN129474508
MCC698937
MCF102117231(CYP24A1)
MTHB126929847
MNI105470644
CSAB103243965(CYP24A1)
CATY105585362
PANU100997369
TGE112632353
MLEU105538302
RRO104662355
RBB108521781
TFN117068948
PTEH111521023
CANG105507983
CJC100393283
SBQ101054511
CIMI108281352(CYP24A1)
ANAN105727531
CSYR103265086
MMUR105864362 105869419
LCAT123622312
PCOQ105811599
OGA100948814
MMU13081(Cyp24a1)
MCAL110289544
MPAH110318266
RNO25279(Cyp24a1)
MCOC116091462
ANU117703542
MUN110545262
CGE100751280
MAUA101827330
PROB127225192
PLEU114704035
MORG121440893
MFOT126508008
AAMP119815492
NGI103735781
HGL101716773
CPOC100728021
CCAN109694681
DORD105991653
DSP122124591
PLOP125353900
NCAR124978047
MMMA107137340
OCU100347441
OPI101526808
TUP102471055
GVR103588022
CFA485935(CYP24A1)
CLUD112674140
VVP112931920
VLG121477768
NPO129495117
AML100479790
UMR103669826
UAH113258741
UAR123799375
ELK111141789
LLV125109083
MPUF101678691
MNP132022040
MLK131807947
NVS122915540
ORO101384402
EJU114225492
ZCA113938600
MLX118024098
NSU110569858
LWW102751252
FCA101096141(CYP24A1)
PYU121019910
PCOO112869096
PBG122467253
PVIV125162613
LRUF124504391
PTG102967619
PPAD109272242
PUC125936486
AJU106970319
HHV120230459
BTA540080(CYP24A1)
BOM102272075
BIU109567562
BBUB102396198
BBIS104988843
CHX102178921
OAS100170323(CYP24)
BTAX128058745
ODA120869048
CCAD122448475
MBEZ129556173
SSC397145(CYP24A1)
CFR102516204
CBAI105071834
CDK105098859
VPC102531787
BACU103015403
BMUS118881970
LVE103082411
OOR101271151
DLE111186695
PCAD102977275
PSIU116740225
NASI112403033
ECB100053452(CYP24A1)
EPZ103554239
EAI106825434
MYB102249295
MYD102772049
MMYO118663454
MLF102432347
MDT132239226
PKL118708044
EFUS103285757
MNA107536509
DRO112304205
SHON118996516
AJM119040651
PDIC114506963
PHAS123815183
MMF118619039
PPAM129070417
HAI109381840
RFQ117015976
PALE102878689
PGIG120603843
PVP105296033
RAY107498143
MJV108390269
TOD119254587
SARA101543781
SETR126019143
LAV100663262
TMU101353460
ETF101646845
DNM101442213
MDO100028177
GAS123233554
SHR100916072
AFZ127548933
PCW110206681
TVP118844580
OAA100078505
GGA395827(CYP24A1)
PCOC116227703
MGP100541378
CJO107323241
TPAI128080918
LMUT125701250
NMEL110408247
APLA101797037
ACYG106041795(CYP24A1)
CATA118248976
AFUL116495811
TGU100226727
LSR110472394
SCAN103818886
PMOA120507065
OTC121342986
PRUF121359459
GFR102044237
FAB101813067
OMA130261171
PHI102111029
PMAJ107213207
CCAE111938004
CCW104687601
CBRC103616823
ETL114056255
ZAB102067744
ZLE135456216
ACHL103801335
SVG106853090
MMEA130582173
HRT120760156
SATI136368699(CYP24A1)
FPG101919538
FCH102046853
CCRI104163872
NNT104412533
SHAB115615252
ACUN113487633
TALA104355745
ACHC115339853
HALD104317033
HLE104833207
AGEN126045322
GCL127023359
CSTI104559611
LDI104340282
MNB103775032
DPUB104302691
AVIT104274781
BRHI104499916
EGZ104132191
NNI104013059
PCRI104024392
PCAO104039545
PADL103919278
AFOR103894637
FGA104069789
GSTE104258977
CLV102098516
MUI104537354
PGUU104464606
PLET104624707
EHS104503318
CMAC104483098
CUCA104057394
TEO104375190
BREG104629802
OHA104328853
ACAR104526380
CPEA104389628
CVF104293941
RTD128916821
AAM106491745
AROW112960579
NPD112949674
TGT104576182
DNE112982887
SCAM104150031
ASN102382614
AMJ102574966(CYP24A1)
CPOO109318764
GGN109292377
PSS102458142
CMY102932138
CCAY125622449
DCC119842129
CPIC101938071
TST117886274
CABI116821477
MRV120379784
ACS100555767 100564552
ASAO132773120
PVT110071817
SUND121927742
PBI103065707
PMUR107287085
CTIG120308207
TSR106547483
PGUT117674844
APRI131195709
PTEX113434347
NSS113410403
VKO123036291
PMUA114599654
PRAF128416477
ZVI118089322
HCG128353023
GJA107119104
STOW125432416
EMC129330710
XLA108700906(cyp24a1.L) 108718538
XTR100496967 100497429(cyp24a1)
NPR108784249 108790437
RTEM120940805
BBUF121001334
BGAR122939129
MUO115456829
GSH117356032
DRE100004700(cyp24a1)
SRX107744352
SANH107666154 107696435
SGH107560513 107587600
CCAR109057669
CAUA113050135 113078343 113104946 113105072
CGIB127959124 128016032
PTET122347370
LROH127167146
OMC131543101
PPRM120493676
RKG130104145
MAMB125273354
CIDE127514698
CERY137011374(cyp24a1)
MASI127446014 127449569
TROS130556927
TDW130425264
MANU129451013
IPU108271496
IFU128615088
PHYP113532087
SMEO124388872
TFD113642663
TVC132844614
TRN134316931
AMEX103030576
CMAO118808505
EEE113571660
CHAR105907715
TRU101077963
TFS130524793
TNGGSTEN00033861G001
LCO104935382
NCC104966082
TBEN117489819
CGOB115008593
PGEO117447336
GACU117539590
EMAC134883524
ELY117257164
EFO125895063
PLEP121959102
SLUC116051531
ECRA117943678
ESP116687595
PFLV114554700
GAT120835793
PPUG119194098
AFB129105552
CLUM117731186
PSWI130209058
MSAM119885885
SCHU122884848
CUD121507546
ALAT119020664
MZE101475325
ONL100690876
OAU116319460
OLA101165632
OML112145619
CSAI133449287
XMA102225814
XCO114135962
XHE116711044
PRET103464673
PFOR103134567
PLAI106960246
PMEI106929021
GAF122833415
PPRL129372875
CVG107097105
CTUL119788661
GMU124856320
NFU107385407
KMR108231477
ALIM106533681
NWH119411875
AOCE111579624
MCEP125006146
CSEM103386736
POV109635373
SSEN122767772
HHIP117761120
HSP118103196
PPLT128448985
SMAU118310037
LCF108873562
SDU111233601
SLAL111660685
XGL120783454
HCQ109507475
SSCV125977385
SBIA133507962
PEE133408898
PTAO133483835
BPEC110171174
MALB109951265
BSPL114856188
SJO128355486
SASA106565076(CP24A) 106583685
STRU115150083 115208378
OTW112255537 112267058
OMY100136661 110493887
OGO124002353 124018524
ONE115125232 115142853
OKI109890306 109891209
OKE118373224 118388929
SALP111961723 111970527
SNH120064455 120065468
CCLU121575591 121577964
ELS105016677
SFM108936451
PKI111835893
AANG118210803
LOC102698913
PSPA121297804 121319232
ARUT117418538 117433450
PSEX120515040
LCM102364004
CMK103191047
RTP109910917
CPLA122560047
HOC132822650
LERI129707428
PMRN116952143
LRJ133354894
ACOO126841906
DVT126895652
HVI124356704
MQU129004834
HAME121870079
CQD128687363
RSAN119392951
RMP119172898
PMEO129595599
GAE121366250 121373112
HRF124134044 124135907
HRJ124282302 124283687 124289154
CANU128183315
OED125677184
LLON135495240
HSY130622697
RES135681004 135696755
RIEOCT59_002479
 » 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
LinkDB

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