CYP24A1 is an enzyme expressed in the
mitochondrion of humans and other species. It catalyzes hydroxylation reactions which lead to the degradation of
1,25-dihydroxyvitamin D3, the physiologically active form of
vitamin D. Hydroxylation of the side chain produces
calcitroic acid and other metabolites which are excreted in
bile. CYP24A1 was identified in the early 1970s and was first thought to be involved in vitamin D metabolism as the renal 25-hydroxyvitamin D3-24-hydroxylase, modifying
calcifediol (25-hydroxyvitamin D) to produce
24,25-dihydroxycholecalciferol (24,25-dihydroxyvitamin D). Subsequent studies using recombinant CYP24A1 showed that it could also catalyze multiple other hydroxylation reactions at the side chain carbons known as C-24 and C-23 in both 25-OH-D3 and the active hormonal form, 1,25-(OH)2D3. It is now considered responsible for the entire five-step, 24-oxidation pathway from 1,25-(OH)2D3 producing calcitroic acid. CYP24A1 also is able to catalyze another pathway which starts with 23-hydroxylation of 1,25-(OH)2D3 and culminates in 1,25-(OH)2D3-26,23-lactone. The side chains of the
ergocalciferol (vitamin D2) derivatives, 25-OH-D2 and 1,25-(OH)2D2, are also hydroxylated by CYP24A1. The structure of CYP24A1 is highly conserved between different species although the balance of functions can differ. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. This enzyme plays an important role in
calcium homeostasis and the vitamin D endocrine system through its regulation of the level of vitamin D3.
Interactive pathway map ==Regulation==