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
HSA: 1591(CYP24A1)
PTR: 746729(CYP24A1)
PPS: 100971976
GGO: 101142284
PON: 100457433
NLE: 100603459
MCC: 698937
MCF: 102117231
CSAB: 103243965(CYP24A1)
CATY: 105585362
PANU: 100997369
RRO: 104662355
RBB: 108521781
TFN: 117068948
PTEH: 111521023
CJC: 100393283
SBQ: 101054511
MMU: 13081(Cyp24a1)
MCAL: 110289544
MPAH: 110318266
RNO: 25279(Cyp24a1)
MCOC: 116091462
MUN: 110545262
CGE: 100751280
PLEU: 114704035
NGI: 103735781
HGL: 101716773
CCAN: 109694681
OCU: 100347441
TUP: 102471055
CFA: 485935(CYP24A1)
VVP: 112931920
VLG: 121477768
AML: 100479790
UMR: 103669826
UAH: 113258741
ORO: 101384402
ELK: 111141789
MPUF: 101678691
EJU: 114225492
MLX: 118024098
FCA: 101096141
PYU: 121019910
PBG: 122467253
PTG: 102967619
PPAD: 109272242
AJU: 106970319
HHV: 120230459
BTA: 540080(CYP24A1)
BOM: 102272075
BIU: 109567562
BBUB: 102396198
CHX: 102178921
OAS: 100170323(CYP24)
ODA: 120869048
CCAD: 122448475
SSC: 397145(CYP24A1)
CFR: 102516204
CBAI: 105071834
CDK: 105098859
BACU: 103015403
LVE: 103082411
OOR: 101271151
DLE: 111186695
PCAD: 102977275
ECB: 100053452(CYP24A1)
EPZ: 103554239
EAI: 106825434
MYB: 102249295
MYD: 102772049
MMYO: 118663454
MNA: 107536509
HAI: 109381840
DRO: 112304205
SHON: 118996516
AJM: 119040651
MMF: 118619039
PALE: 102878689
PGIG: 120603843
RAY: 107498143
MJV: 108390269
TOD: 119254587
LAV: 100663262
TMU: 101353460
MDO: 100028177
SHR: 100916072
PCW: 110206681
OAA: 100078505
GGA: 395827(CYP24A1)
PCOC: 116227703
MGP: 100541378
CJO: 107323241
NMEL: 110408247
APLA: 101797037
ACYG: 106041795
TGU: 100226727
LSR: 110472394
SCAN: 103818886
PMOA: 120507065
GFR: 102044237
FAB: 101813067
PHI: 102111029
PMAJ: 107213207
CCAE: 111938004
CCW: 104687601
ETL: 114056255
FPG: 101919538
FCH: 102046853
CLV: 102098516
EGZ: 104132191
NNI: 104013059
ACUN: 113487633
PADL: 103919278
AAM: 106491745
AROW: 112960579
NPD: 112949674
DNE: 112982887
ASN: 102382614
AMJ: 102574966(CYP24A1)
CPOO: 109318764
GGN: 109292377
PSS: 102458142
CMY: 102932138
CPIC: 101938071
TST: 117886274
CABI: 116821477
PVT: 110071817
PBI: 103065707
PMUR: 107287085
TSR: 106547483
PGUT: 117674844
PMUA: 114599654
ZVI: 118089322
GJA: 107119104
XLA: 108700906(cyp24a1.L) 108718538
XTR: 100496967 100497429(cyp24a1)
DRE: 100004700(cyp24a1)
SRX: 107744352
CCAR: 109057669
IPU: 108271496(CYP24A1)
PHYP: 113532087
AMEX: 103030576
EEE: 113571660
TRU: 101077963
LCO: 104935382
NCC: 104966082
CGOB: 115008593
ELY: 117257164
PLEP: 121959102
SLUC: 116051531
ECRA: 117943678
PFLV: 114554700
GAT: 120835793
MSAM: 119885885
CUD: 121507546
MZE: 101475325
ONL: 100690876
OAU: 116319460
OLA: 101165632
OML: 112145619
XMA: 102225814
XCO: 114135962
XHE: 116711044
PRET: 103464673
CVG: 107097105
CTUL: 119788661
NFU: 107385407
KMR: 108231477
ALIM: 106533681
AOCE: 111579624
CSEM: 103386736
POV: 109635373
LCF: 108873562
SDU: 111233601
SLAL: 111660685
XGL: 120783454
HCQ: 109507475
BPEC: 110171174
MALB: 109951265
SASA: 106565076(CP24A) 106583685
ELS: 105016677
SFM: 108936451
PKI: 111835893
AANG: 118210803
LOC: 102698913
LCM: 102364004
CMK: 103191047
RTP: 109910917
BBEL: 109469838
HAME: 121870079
RSAN: 119392951
RMP: 119172898
 » 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

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