ExplorEnz: EC 1.14.15.16

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1.14.15.16

Accepted name:

vitamin D₃ 24-hydroxylase

Reaction:

(1) calcitriol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = calcitetrol + 2 oxidized adrenodoxin + H₂O
(2) calcidiol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = secalciferol + 2 oxidized adrenodoxin + H₂O

For diagram of calciferol biosynthesis, click here

Glossary:

calcidiol = 25-hydroxyvitamin D₃ = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
calcitriol = 1α,25-dihydroxyvitamin D₃ = (1S,3R,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-1,3,25-triol
calcitetrol = 1α,24R,25-trihydroxyvitamin D₃ = (1S,3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-1,3,24,25-tetrol
secalciferol = (24R)-24,25-dihydroxycalciol = 24R,25-dihydroxyvitamin D₃ = (3R,5Z,7E,24R)-9,10-seco-5,7,10(19)-cholestatriene-3,24,25-triol

Other name(s):

CYP24A1

Systematic name:

calcitriol,adrenodoxin:oxygen oxidoreductase (24-hydroxylating)

Comments:

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.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB

References:

1.	Masuda, S., Strugnell, S.A., Knutson, J.C., St-Arnaud, R. and Jones, G. Evidence for the activation of 1α-hydroxyvitamin D₂ by 25-hydroxyvitamin D-24-hydroxylase: delineation of pathways involving 1α,24-dihydroxyvitamin D₂ and 1α,25-dihydroxyvitamin D₂. Biochim. Biophys. Acta 1761 (2006) 221–234. [DOI] [PMID: 16516540]
2.	Hamamoto, H., Kusudo, T., Urushino, N., Masuno, H., Yamamoto, K., Yamada, S., Kamakura, M., Ohta, M., Inouye, K. and Sakaki, T. 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. Mol. Pharmacol. 70 (2006) 120–128. [DOI] [PMID: 16617161]
3.	Sakaki, T., Kagawa, N., Yamamoto, K. and Inouye, K. Metabolism of vitamin D₃ by cytochromes P₄₅₀. Front. Biosci. 10 (2005) 119–134. [PMID: 15574355]
4.	Prosser, D.E., Kaufmann, M., O'Leary, B., Byford, V. and Jones, G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1α,25-(OH)₂D₃-26,23-lactone. Proc. Natl. Acad. Sci. USA 104 (2007) 12673–12678. [DOI] [PMID: 17646648]
5.	Kusudo, T., Sakaki, T., Abe, D., Fujishima, T., Kittaka, A., Takayama, H., Hatakeyama, S., Ohta, M. and Inouye, K. Metabolism of A-ring diastereomers of 1α,25-dihydroxyvitamin D₃ by CYP24A1. Biochem. Biophys. Res. Commun. 321 (2004) 774–782. [DOI] [PMID: 15358094]
6.	Sawada, N., Kusudo, T., Sakaki, T., Hatakeyama, S., Hanada, M., Abe, D., Kamao, M., Okano, T., Ohta, M. and Inouye, K. Novel metabolism of 1α,25-dihydroxyvitamin D₃ with C₂₄-C₂₅ bond cleavage catalyzed by human CYP24A1. Biochemistry 43 (2004) 4530–4537. [DOI] [PMID: 15078099]
7.	Prosser, D.E. and Jones, G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 29 (2004) 664–673. [DOI] [PMID: 15544953]

[EC 1.14.15.16 created 2011 as EC 1.14.13.126, transferred 2016 to EC 1.14.15.16]