Reaction: (1) calcitriol + NADPH + H+ + O2 = calcitetrol + NADP+ + H2O
(2) calcidiol + NADPH + H+ + O2 = secalciferol + NADP+ + H2O
For diagram of reaction click here.
Glossary: calcidiol = 25-hydroxyvitamin D3
calcitriol = 1α,25-dihydroxyvitamin D3
calcitetrol = 1α,24R,25-trihydroxyvitamin D3
secalciferol = (24R)-24,25-dihydroxycalciol = 24R,25-dihydroxyvitamin D3
Other name(s): CYP24A1
Systematic name: calcitriol,NADPH:oxygen oxidoreductase (24-hydroxylating)
Comments: A heme-thiolate enzyme (P-450). The second donor, NADPH, donates electrons through EC 1.18.1.2, ferredoxinÑNADP+ 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.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
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. [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. [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. [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. [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 1 α,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1. Biochemistry 43 (2004) 4530-4537. [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. [PMID: 15544953]