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

Arch Biochem Biophys. 2012 Jul 1;523(1):9-18. doi: 10.1016/j.abb.2011.11.003. Epub 2011 Nov 12.

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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biocatalysis
  • Disease / genetics
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Steroid Hydroxylases / chemistry
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism*
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • Vitamin D
  • Fibroblast Growth Factors
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase