suck pdf from google scholar
PDF vom PMID11172626  :  Publisher
PDF vom PMID11172626
suck pdf from library genesis
English Wikipedia

Nephropedia Template TP (

Twit Text

  • DeepDyve
  • Pubget Overpricing

  • lüll
  • Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review)
  • Wikvall K
  • Int J Mol Med 2001[Feb]; 7 (2): 201-9
  • The formation of 1alpha,25-dihydroxyvitamin D3 requires a 25-hydroxylation followed by a 1alpha-hydroxylation catalyzed by cytochrome P450 (CYP) enzymes in liver and kidney. The aim of this review is to give a brief summary of our research on the cytochrome P450 enzymes catalyzing the 25-hydroxylation and 1alpha-hydroxylation and to discuss the results in relation to other published literature on these enzymes. Two hepatic P450 enzymes catalyzing 25-hydroxylation of vitamin D3 exist in mammalian liver - one mitochondrial and one microsomal. The mitochondrial vitamin D3 25-hydroxylase is apparently identical with CYP27A, an obligatory enzyme in bile acid biosynthesis in liver. The microsomal 25-hydroxylase has been purified to apparent homogeneity from pig liver. The enzyme catalyzed 25-hydroxylation of vitamin D3, 1alpha-hydroxyvitamin D3, vitamin D2 and 1alpha-hydroxyvitamin D2. A cDNA encoding pig liver microsomal vitamin D3 25-hydroxylase has been isolated in this laboratory. The primary structure of vitamin D3 25-hydroxylase shows 70-80% identity with members of the CYP2D subfamily and has been designated CYP2D25. Three different 1alpha-hydroxylating cytochromes P450 in kidney, i.e. CYP27A, CYP27B and a microsomal 1alpha-hydroxylase, have been described. Mitochondrial cytochrome P450, catalyzing 1alpha-hydroxylation and 27-hydroxylation but not 24-hydroxylation of 25-hydroxyvitamin D3, was partially purified from pig kidney. Purification and inhibition experiments as well as experiments with a monoclonal antibody against CYP27A indicated that one single enzyme catalyzes both 1alpha- and 27-hydroxylation. Treatment of rats with a single i.v. dose of 1alpha,25-dihydroxyvitamin D3 resulted in a marked suppression of CYP27A mRNA levels in kidney. The results suggest a role for CYP27A as a renal mitochondrial 1alpha-hydroxylase. Subsequently, several research groups reported the isolation of cDNA encoding mouse, rat and human kidney 25-hydroxyvitamin D3 1alpha-hydroxylase. The amino acid sequences deduced from these cDNA clones were similar but differed from that of CYP27A. This 1alpha-hydroxylase constitutes a new CYP27 subfamily, CYP27B. The expression of CYP27B was found to be influenced by vitamin D status and parathyroid hormone. Mutations in the CYP27B gene have been identified in patients with pseudovitamin D-deficiency rickets. A microsomal P450 catalyzing 1alpha-hydroxylation of 25-hydroxyvitamin D3 has been purified to apparent homogeneity from pig kidney. This finding demonstrate the presence of a microsomal 1alpha-hydroxylase in addition to the mitochondrial 1alpha-hydroxylases in kidney. The relative importance and regulation of the different renal 1alpha-hydroxylases in the bioactivation of vitamin D3 under normal and pathological conditions will be subject for future studies.
  • |Animals[MESH]
  • |Calcitriol/metabolism[MESH]
  • |Cholestanetriol 26-Monooxygenase[MESH]
  • |Cytochrome P-450 Enzyme System/*physiology[MESH]
  • |Humans[MESH]
  • |Hydroxylation[MESH]
  • |Steroid Hydroxylases/metabolism[MESH]
  • |Vitamin D/*metabolism[MESH]

  • *{{pmid11172626}}
    *<b>[ Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review) ]</b> Int J Mol Med 2001; 7(2) ; 201-9 Wikvall K


    Nephropedia PMID record

    Deutsche Wikipedia - im Artikel

    Hier den unten stehenden Textblock hineinkopieren

    Int J Mol Med

    201 2.7 2001