کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1925534 | 1536390 | 2012 | 10 صفحه PDF | دانلود رایگان |
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.
► Synopsis of anabolic and catabolic pathways of vitamin D stressing role of CYP24A1.
► CYP24A1 structure based upon rat crystal structure, homology models and mutagenesis.
► Natural mutations of human CYP24A1 cause idiopathic infantile hypercalcemia.
► Physiological role of CYP24A1 and regulation by 1,25-(OH)2D3, PTH and FGF-23.
► Upregulated CYP24A1 in chronic kidney disease and use of CYP24A1 inhibitors.
Journal: Archives of Biochemistry and Biophysics - Volume 523, Issue 1, 1 July 2012, Pages 9–18