Vitamin D 25-hydroxylase

Definition:

A cytochrome P450 monooxygenase involved in activation of vitamin D precursors. Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).

References:

[1]. Raku Shinkyo, et al. Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun. 2004 Nov 5;324(1):451-7. [Content Brief]

[2]. Natallia Strushkevich, et al. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008 Jun 27;380(1):95-106. [Content Brief]

[3]. Jeffrey B Cheng, et al. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003 Sep 26;278(39):38084-93. [Content Brief]

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