Cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) (CYP27B1 and CYP24A1)

Cytochrome P450 family enzymes CYP27B1 and CYP24A1 are key regulators of vitamin D metabolism. - CYP27B1, also known as 25-hydroxyvitamin D(3) 1-alpha-hydroxylase, is a mitochondrial cytochrome P450 monooxygenase that catalyzes the final activation step converting circulating calcifediol [25(OH)D] into its biologically active form, calcitriol [1,25(OH)₂D]. This reaction is crucial for calcium absorption and bone health. Its activity is regulated by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcium, phosphate status, and feedback from calcitriol itself. - CYP24A1, known as Vitamin D(3) 24-hydroxylase, is responsible for initiating the catabolism/inactivation pathway by converting both calcifediol [25(OH)D] and calcitriol [1,25(OH)₂D] into less active metabolites such as 24,25-dihydroxyvitamin D. This process prevents excess accumulation of active vitamin D compounds. Mutations leading to loss-of-function cause elevated serum calcium due to impaired breakdown—manifesting clinically as hypercalcemia or kidney stones—and play a role in chronic kidney disease-mineral bone disorder pathophysiology. Both enzymes are widely expressed beyond classical target tissues like kidney—appearing also in intestine and various extrarenal sites—and their dysregulation has been implicated not only in mineral disorders but also cancer progression through altered local production/degradation of bioactive vitamin Ds within tissues such as breast tumors. Their activities represent important therapeutic targets for diseases involving abnormal mineral homeostasis.

Other names

CYP27B1: 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrialCYP27B1: Vitamin D-activating enzymeCYP24A1: Vitamin D(3) 24-hydroxylaseCYP24A1: Calcidiol 24-hydroxylase

Drugs targeting these enzymes typically act by: - Inhibiting or enhancing the conversion between inactive/active/inactive forms of vitamin D metabolites. - CYP27B1 catalyzes the activation step from calcifediol to calcitriol. - CYP24A1 catalyzes the inactivation/catabolic steps from active forms to less active/inactive metabolites.