**2.3. Hydroxylase enzymes**

The formation, activation, and catabolism of 25(OH)D are complex processes, which involve mitochondrial and microsomal cytochrome P450 enzymes. In humans, four cytochrome P450 enzymes, CYP2R1, CYP3A4, CYP27A1, and CYP2J2, [44–47] possess 25-hydroxylase activity, with CYP2R1 being the most specific. Hydroxylation in the 1α-position is effected by the mitochondrial CYP27B1. This process was classically located to the kidney, but recently, extrarenal 1α-hydroxylase activity has been described in several other tissues [48]. 1,25(OH)2D stimulates its own degradation by induction of the 24-hydroxylase (CYP24A1), which catabolizes 25(OH)D and 1,25(OH)2D to calcitroic acid and other inactive metabolites [49].
