The Enzyme Database

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Accepted name: vitamin D 25-hydroxylase
Reaction: calciol + O2 + [reduced NADPH—hemoprotein reductase] = calcidiol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of calciferol biosynthesis, click here
Glossary: calciol = cholecalciferol = vitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol
Other name(s): vitamin D2 25-hydroxylase; vitamin D3 25-hydroxylase; CYP2R1
Systematic name: calciol,NADPH—hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)
Comments: A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D3. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4]. The direct electron donor to the enzyme is EC, NADPH—hemoprotein reductase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
1.  Cheng, J.B., Motola, D.L., Mangelsdorf, D.J. and Russell, D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084–38093. [DOI] [PMID: 12867411]
2.  Shinkyo, R., Sakaki, T., Kamakura, M., Ohta, M. and Inouye, K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451–457. [DOI] [PMID: 15465040]
3.  Strushkevich, N., Usanov, S.A., Plotnikov, A.N., Jones, G. and Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D3. J. Mol. Biol. 380 (2008) 95–106. [DOI] [PMID: 18511070]
4.  Zhu, J. and DeLuca, H.F. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch. Biochem. Biophys. 523 (2012) 30–36. [DOI] [PMID: 22310641]
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