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
NLE100603459
MCC698937
MCF102117231(CYP24A1)
MTHB126929847
CSAB103243965(CYP24A1)
CATY105585362
PANU100997369
TGE112632353
RRO104662355
RBB108521781
TFN117068948
PTEH111521023
CJC100393283
SBQ101054511
CSYR103265086
MMUR105864362 105869419
LCAT123622312
OGA100948814
MMU13081(Cyp24a1)
MCAL110289544
MPAH110318266
RNO25279(Cyp24a1)
MCOC116091462
MUN110545262
CGE100751280
MAUA101827330
PLEU114704035
MORG121440893
MFOT126508008
AAMP119815492
NGI103735781
HGL101716773
CPOC100728021
CCAN109694681
DORD105991653
DSP122124591
NCAR124978047
OCU100347441
OPI101526808
TUP102471055
CFA485935(CYP24A1)
CLUD112674140
VVP112931920
VLG121477768
AML100479790
UMR103669826
UAH113258741
UAR123799375
ELK111141789
LLV125109083
MPUF101678691
ORO101384402
EJU114225492
ZCA113938600
MLX118024098
NSU110569858
FCA101096141
PYU121019910
PBG122467253
LRUF124504391
PTG102967619
PPAD109272242
AJU106970319
HHV120230459
BTA540080(CYP24A1)
BOM102272075
BIU109567562
BBUB102396198
CHX102178921
OAS100170323(CYP24)
ODA120869048
CCAD122448475
SSC397145(CYP24A1)
CFR102516204
CBAI105071834
CDK105098859
VPC102531787
BACU103015403
LVE103082411
OOR101271151
DLE111186695
PCAD102977275
PSIU116740225
ECB100053452(CYP24A1)
EPZ103554239
EAI106825434
MYB102249295
MYD102772049
MMYO118663454
MLF102432347
MNA107536509
PKL118708044
HAI109381840
DRO112304205
SHON118996516
AJM119040651
PDIC114506963
PHAS123815183
MMF118619039
RFQ117015976
PALE102878689
PGIG120603843
PVP105296033
RAY107498143
MJV108390269
TOD119254587
SARA101543781
LAV100663262
TMU101353460
DNM101442213
MDO100028177
GAS123233554
SHR100916072
PCW110206681
OAA100078505
GGA395827(CYP24A1)
PCOC116227703
MGP100541378
CJO107323241
NMEL110408247
APLA101797037
ACYG106041795
AFUL116495811
TGU100226727
LSR110472394
SCAN103818886
PMOA120507065
OTC121342986
PRUF121359459
GFR102044237
FAB101813067
PHI102111029
PMAJ107213207
CCAE111938004
CCW104687601
CBRC103616823
ETL114056255
ZAB102067744
ACHL103801335
FPG101919538
FCH102046853
CLV102098516
EGZ104132191
NNI104013059
PLET104624707
PCRI104024392
PCAO104039545
ACUN113487633
TALA104355745
PADL103919278
AFOR103894637
ACHC115339853
HALD104317033
CCRI104163872
CSTI104559611
EHS104503318
CMAC104483098
MUI104537354
FGA104069789
GSTE104258977
LDI104340282
MNB103775032
OHA104328853
NNT104412533
DPUB104302691
PGUU104464606
ACAR104526380
AVIT104274781
CVF104293941
CUCA104057394
AAM106491745
AROW112960579
NPD112949674
TGT104576182
DNE112982887
SCAM104150031
ASN102382614
AMJ102574966(CYP24A1)
CPOO109318764
GGN109292377
PSS102458142
CMY102932138
CPIC101938071
TST117886274
CABI116821477
MRV120379784
ACS100555767 100564552
PVT110071817
SUND121927742
PBI103065707
PMUR107287085
CTIG120308207
TSR106547483
PGUT117674844
VKO123036291
PMUA114599654
ZVI118089322
GJA107119104
STOW125432416
XLA108700906(cyp24a1.L) 108718538
XTR100496967 100497429(cyp24a1)
NPR108784249 108790437
RTEM120940805
BBUF121001334
BGAR122939129
DRE100004700(cyp24a1)
SRX107744352
SANH107666154 107696435
SGH107560513 107587600
CCAR109057669
CAUA113050135 113078343 113104946 113105072
PPRM120493676
MAMB125273354
IPU108271496
PHYP113532087
SMEO124388872
TFD113642663
AMEX103030576
EEE113571660
TRU101077963
TNGGSTEN00033861G001
LCO104935382
NCC104966082
CGOB115008593
ELY117257164
EFO125895063
PLEP121959102
SLUC116051531
ECRA117943678
ESP116687595
PFLV114554700
GAT120835793
PPUG119194098
MSAM119885885
CUD121507546
ALAT119020664
MZE101475325
ONL100690876
OAU116319460
OLA101165632
OML112145619
XMA102225814
XCO114135962
XHE116711044
PRET103464673
PFOR103134567
PLAI106960246
PMEI106929021
GAF122833415
CVG107097105
CTUL119788661
GMU124856320
NFU107385407
KMR108231477
ALIM106533681
NWH119411875
AOCE111579624
MCEP125006146
CSEM103386736
POV109635373
SSEN122767772
HHIP117761120
HSP118103196
LCF108873562
SDU111233601
SLAL111660685
XGL120783454
HCQ109507475
BPEC110171174
MALB109951265
BSPL114856188
SASA106565076(CP24A) 106583685
STRU115150083 115208378
OTW112255537 112267058
OMY100136661 110493887
OGO124002353 124018524
ONE115125232 115142853
SALP111961723 111970527
SNH120064455 120065468
CCLU121575591 121577964
ELS105016677
SFM108936451
PKI111835893
AANG118210803
LOC102698913
PSPA121297804 121319232
ARUT117418538 117433450
LCM102364004
CMK103191047
RTP109910917
HAME121870079
RSAN119392951
RMP119172898
GAE121366250 121373112
HRF124126383 124134044 124135907 124143865
HRJ124282302 124283687 124289154
XEN124454605
 » 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

DBGET integrated database retrieval system