25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D

Abstract

CYP24A1 is the cytochrome P450 component of the 25-hydroxyvitamin D(3)-24-hydroxylase enzyme that catalyzes the conversion of 25-hydroxyvitamin D(3) (25-OH-D(3)) and 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) into 24-hydroxylated products, which constitute the degradation of the vitamin D molecule. This review focuses on recent data in the CYP24A1 field, including biochemical, physiological and clinical developments. Notable among these are: the first crystal structure for rat CYP24A1; mutagenesis studies which change the regioselectivity of the enzyme; and the finding that natural inactivating mutations of CYP24A1 cause the genetic disease idiopathic infantile hypercalcemia (IIH). The review also discusses the emerging correlation between rising serum phosphate/FGF-23 levels and increased CYP24A1 expression in chronic kidney disease, which in turn underlies accelerated degradation of both serum 25-OH-D(3) and 1,25-(OH)(2)D(3) in this condition. This review concludes by evaluating the potential clinical utility of blocking this enzyme with CYP24A1 inhibitors in various disease states.