KEGG   ENZYME: 1.14.15.16Help
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
BRITE hierarchy
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)
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)
RRO: 104662355
RBB: 108521781
CJC: 100393283
SBQ: 101054511
MMU: 13081(Cyp24a1)
RNO: 25279(Cyp24a1)
CGE: 100751280
NGI: 103735781
HGL: 101716773
CCAN: 109694681
OCU: 100347441
TUP: 102471055
CFA: 485935(CYP24A1)
AML: 100479790
UMR: 103669826
ORO: 101384402
FCA: 101096141
PTG: 102967619
AJU: 106970319
BTA: 540080(CYP24A1)
BOM: 102272075
BIU: 109567562
PHD: 102325922
CHX: 102178921
OAS: 100170323(CYP24)
SSC: 397145(CYP24A1)
CFR: 102516204
CDK: 105098859
BACU: 103015403
LVE: 103082411
OOR: 101271151
ECB: 100053452(CYP24A1)
EPZ: 103554239
EAI: 106825434
MYD: 102772049
RSS: 109444603
PALE: 102878689
LAV: 100663262
TMU: 101353460
MDO: 100028177
SHR: 100916072
OAA: 100078505
GGA: 395827(CYP24A1)
MGP: 100541378
CJO: 107323241
APLA: 101797037
ACYG: 106041795
TGU: 100226727
GFR: 102044237
FAB: 101813067
PHI: 102111029
PMAJ: 107213207
CCW: 104687601
FPG: 101919538
FCH: 102046853
CLV: 102098516
EGZ: 104132191
AAM: 106491745
ASN: 102382614
AMJ: 102574966(CYP24A1)
PSS: 102458142
CPIC: 101938071
PVT: 110071817
PBI: 103065707
GJA: 107119104
XTR: 100496967 100497429(cyp24a1)
DRE: 100004700(cyp24a1)
CCAR: 109057669
IPU: 108271496(CYP24A1)
AMEX: 103030576
TRU: 101077963
LCO: 104935382
NCC: 104966082
MZE: 101475325
OLA: 101165632
XMA: 102225814
PRET: 103464673
NFU: 107385407
CSEM: 103386736
LCF: 108873562
HCQ: 109507475
BPEC: 110171174
SASA: 106565076(CP24A) 106583685
ELS: 105016677
SFM: 108936451
LCM: 102364004
CMK: 103191047
 » show all
Taxonomy
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)
  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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