Metabolism of vitamin D by human microsomal CYP2R1

Biochem Biophys Res Commun. 2004 Nov 5;324(1):451-7. doi: 10.1016/j.bbrc.2004.09.073.

Abstract

The activation of vitamin D requires 25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney. However, it remains unclear which enzyme is relevant to vitamin D 25-hydroxylation. Recently, human CYP2R1 has been reported to be a potential candidate for a hepatic vitamin D 25-hydroxylase. Thus, vitamin D metabolism by CYP2R1 was compared with human mitochondrial CYP27A1, which used to be considered a physiologically important vitamin D(3) 25-hydroxylase. A clear difference was observed between CYP2R1 and CYP27A1 in the metabolism of vitamin D(2). CYP2R1 hydroxylated vitamin D(2) at the C-25 position while CYP27A1 hydroxylated it at positions C-24 and C-27. The K(m) and k(cat) values for the CYP2R1-dependent 25-hydroxylation activity toward vitamin D(3) were 0.45microM and 0.97min(-1), respectively. The k(cat)/K(m) value of CYP2R1 was 26-fold higher than that of CYP27A1. These results strongly suggest that CYP2R1 plays a physiologically important role in the vitamin D 25-hydroxylation in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholestanetriol 26-Monooxygenase
  • Cytochrome P450 Family 2
  • Humans
  • Mass Spectrometry
  • Microsomes / metabolism*
  • Molecular Structure
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism*
  • Vitamin D / chemistry
  • Vitamin D / metabolism*

Substances

  • Recombinant Proteins
  • Vitamin D
  • Steroid Hydroxylases
  • Cytochrome P450 Family 2
  • CYP2R1 protein, human
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase