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

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• 作者：Glenville Jones ; ^{gj1@queensu.ca} ; David E. Prosser ; Martin Kaufmann
• 关键词：CYP24A1 ; 25-Hydroxyvitamin D3 ; 1 ; 25-Dihydroxyvitamin D3 ; Catabolism ; Gene mutations ; Idiopathic infantile hypercalcemia ; CYP24A1 null-mouse ; FGF-23
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：2012
• 期刊代码：116_00039861
• 类别：ch
• 出版时间：1 July, 2012
• 卷：523
• 期：1
• 页码：9-18
• 文件大小：2322 K

摘要

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.