Vitamin D 25-hydroxylase – Four decades of searching, are we there yet?

Bioactivation of vitamin D3 involves 25-hydroxylation and subsequent 1α-hydroxylation to produce 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active hormone. Six cytochrome P450 enzymes (CYP27A1, CYP2R1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) catalyzing the initial 25-hydroxylation step are reviewed, and their physiological relevance as vitamin D 25-hydroxylases in vivo is discussed.