title: 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.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6. gj1@queensu.ca
authors.forename: Glenville
authors.initials: G
authors.lastname: Jones
authors.forename: David E
authors.initials: DE
authors.lastname: Prosser
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055162:Biocatalysis; D004194:Disease / Q000235:genetics; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013250:Steroid Hydroxylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase