KEGG   ENZYME: 1.14.13.126Help
Entry
EC 1.14.13.126              Enzyme                                 
Name
vitamin D3 24-hydroxylase;
CYP24A1
Class
Oxidoreductases;
Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
calcitriol,NADPH:oxygen oxidoreductase (24-hydroxylating)
Reaction(IUBMB)
(1) calcitriol + NADPH + H+ + O2 = calcitetrol + NADP+ + H2O [RN:R09515];
(2) calcidiol + NADPH + H+ + O2 = secalciferol + NADP+ + H2O [RN:R09516]
Reaction(KEGG)
Substrate
calcitriol [CPD:C01673];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007];
calcidiol [CPD:C01561]
Product
calcitetrol [CPD:C18231];
NADP+ [CPD:C00006];
H2O [CPD:C00001];
secalciferol [CPD:C07712]
Comment
A heme-thiolate enzyme (P-450). The second donor, NADPH, donates electrons through EC 1.18.1.2, ferredoxin--NADP+ reductase and a [2Fe-2S] ferredoxin. 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.
Pathway
Steroid biosynthesis
Metabolic pathways
Orthology
K07436  
cytochrome P450, family 24, subfamily A, polypeptide 1 (vitamin D3 24-hydroxylase)
Genes
HSA: 
1591(CYP24A1)
PTR: 
PPS: 
GGO: 
PON: 
MCC: 
MMU: 
13081(Cyp24a1)
RNO: 
25279(Cyp24a1)
CFA: 
485935(CYP24A1)
AML: 
FCA: 
101096141(CYP24A1)
BTA: 
540080(CYP24A1)
SSC: 
397145(CYP24A1)
ECB: 
100053452
MDO: 
100028177
SHR: 
100916072
OAA: 
100078505
GGA: 
395827(CYP24A1)
MGP: 
100541378
TGU: 
100226727
ACS: 
100564552
XTR: 
100497429
DRE: 
100004700(cyp24a1)
TRU: 
101077963
OLA: 
101165632
TAD: 
TRIADDRAFT_56952
 » 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 (2006) 221-34.
  Organism
Homo sapiens [GN:hsa]
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 (2006) 120-8.
  Organism
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno]
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 (2005) 119-34.
  Organism
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno]
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 (2007) 12673-8.
  Organism
Homo sapiens [GN:hsa]
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 (2004) 774-82.
  Organism
Homo sapiens [GN:hsa], Rattus norvegicus [GN:rno]
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 (2004) 4530-7.
  Organism
Homo sapiens [GN:hsa]
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 (2004) 664-73.
  Organism
Homo sapiens [GN:hsa]
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
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