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

G Jones, DE Prosser, M Kaufmann - Archives of biochemistry and …, 2012 - Elsevier
G Jones, DE Prosser, M Kaufmann
Archives of biochemistry and biophysics, 2012Elsevier
CYP24A1 is the cytochrome P450 component of the 25-hydroxyvitamin D3-24-hydroxylase
enzyme that catalyzes the conversion of 25-hydroxyvitamin D3 (25-OH-D3) and 1, 25-
dihydroxyvitamin D3 (1, 25-(OH) 2D3) 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 …
CYP24A1 is the cytochrome P450 component of the 25-hydroxyvitamin D3-24-hydroxylase enzyme that catalyzes the conversion of 25-hydroxyvitamin D3 (25-OH-D3) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) 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-D3 and 1,25-(OH)2D3 in this condition. This review concludes by evaluating the potential clinical utility of blocking this enzyme with CYP24A1 inhibitors in various disease states.
Elsevier