25-hydroxyvitamin D-1-alpha-hydroxylase (CYP27B1) (CYP27B1)

25-hydroxyvitamin D-1-alpha-hydroxylase, primarily encoded by the CYP27B1 gene, is a critical mitochondrial cytochrome P450 enzyme responsible for the bioactivation of vitamin D [UniProt: P37227]. It catalyzes the conversion of 25-hydroxyvitamin D (calcidiol) into 1,25-dihydroxyvitamin D (calcitriol), which is the high-affinity ligand for the vitamin D receptor [NCBI Gene: 1594]. While its primary site of expression is the renal proximal tubule, where it is tightly regulated by parathyroid hormone and fibroblast growth factor 23, it is also found in extra-renal tissues such as macrophages, skin, and placenta [StatPearls: Vitamin D Deficiency]. Dysregulation or genetic mutations in this enzyme are linked to vitamin D-dependent rickets type 1A and contribute to mineral metabolism disorders in chronic kidney disease [PubMed: 9300004]. Furthermore, its ectopic expression in granulomatous diseases like sarcoidosis can lead to autonomous calcitriol production and clinical hypercalcemia [PubMed: 25207354]. Therapeutic strategies involve the use of active vitamin D analogs to bypass the enzyme or inhibitors like ketoconazole to manage excessive activity in specific disease states [StatPearls: Vitamin D Deficiency].

Other names

Cytochrome P450 family 27 subfamily B member 11-alpha-OHaseCalcidiol 1-monooxygenaseP450VD1-alphaCP27B

Catalyzes the rate-limiting step in vitamin D activation by hydroxylating 25-hydroxyvitamin D at the 1-alpha position to produce the active hormone 1,25-dihydroxyvitamin D.