Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) (CYP24A1)

Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) is a mitochondrial enzyme that serves as the primary catabolic regulator of vitamin D endocrine signaling [UniProt: Q07973]. It catalyzes the multi-step 24-oxidation pathway that converts the active hormone 1,25-dihydroxyvitamin D3 (calcitriol) and its precursor 25-hydroxyvitamin D3 into inactive, water-soluble metabolites like calcitroic acid for excretion [NCBI Gene: 1591]. By controlling the degradation of these metabolites, CYP24A1 plays a critical role in maintaining systemic calcium and phosphorus homeostasis [PubMed: 21642993]. In clinical medicine, loss-of-function mutations in CYP24A1 lead to idiopathic infantile hypercalcemia, a condition characterized by dangerously high blood calcium levels and renal calcification [PubMed: 21642993]. Conversely, the enzyme is frequently upregulated in various malignancies, including breast and colorectal cancers, where it acts as an oncogene by depleting the anti-proliferative and pro-differentiating effects of calcitriol within the tumor microenvironment [PubMed: 24518150]. Consequently, CYP24A1 is a significant therapeutic target; inhibitors are being developed to enhance the efficacy of vitamin D analogs in treating chronic kidney disease and to restore the tumor-suppressive signaling of vitamin D in cancer therapy [PubMed: 22459403].

Other names

1,25-dihydroxyvitamin D3 24-hydroxylaseVitamin D3 24-hydroxylaseCYP2424-OHaseCytochrome P450 24-hydroxylase

Inhibition of CYP24A1 prevents the 24-hydroxylation and subsequent metabolic inactivation of 1,25-dihydroxyvitamin D3 (calcitriol), thereby increasing its local or systemic concentration and prolonging its biological activity through the vitamin D receptor.