23-Keto-25-hydroxyvitamin D3: a vitamin D3 metabolite with high affinity for the 1,25-dihydroxyvitamin D specific cytosol receptor

Biochemistry. 1983 Jan 18;22(2):245-50. doi: 10.1021/bi00271a002.


A new metabolite of 23,25-dihydroxyvitamin D3 has been generated with kidney homogenates prepared from vitamin D treated chicks. The metabolite was purified with three high-performance liquid chromatographic steps and was identified as 23-keto-25-hydroxyvitamin D3 by ultraviolet absorption spectroscopy, mass spectrometry, and chemical reactivity. The R stereoisomer of 23,25-dihydroxyvitamin D3 was 10-fold more effective as an in vitro precursor to 23-keto-25-hydroxyvitamin D3 than was the naturally occurring S stereoisomer. Approximately 500 ng of 23-keto-25-hydroxyvitamin D3 was necessary to produce the same degree of intestinal-calcium transport as 25 ng of vitamin D3--a difference of about 20-fold. 23-Keto-25-hydroxyvitamin D3 was not active at stimulating bone calcium resorption at the doses and times tested. This new vitamin D3 metabolite, however, had greater affinity than 25-hydroxyvitamin D3 to both the rat plasma vitamin D binding protein and the 1,25-dihydroxyvitamin D specific cytosol receptor. Heretofore, only 1 alpha-hydroxylated metabolites of 25-hydroxyvitamin D3 or analogues possessing a pseudo 1 alpha-hydroxy group were known to bind to the 1,25-dihydroxyvitamin D receptor with higher affinity than 25-hydroxyvitamin D3. Ketone formation at the 23 position, therefore, is the first side-chain modification of 25-hydroxyvitamin D3 that results in enhanced binding to the 1,25-dihydroxyvitamin D receptor binding protein.

Publication types

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

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Calcifediol / metabolism
  • Calcium / metabolism
  • Carrier Proteins / metabolism
  • Chemical Phenomena
  • Chemistry
  • Chickens
  • Cytosol / metabolism
  • Dihydroxycholecalciferols / metabolism
  • Duodenum / metabolism
  • Hydroxycholecalciferols / metabolism*
  • Hydroxycholecalciferols / pharmacology
  • Kidney / metabolism
  • Male
  • Mass Spectrometry
  • Molecular Conformation
  • Rats
  • Receptors, Calcitriol
  • Receptors, Steroid / metabolism*
  • Spectrophotometry, Ultraviolet
  • Vitamin D-Binding Protein


  • Carrier Proteins
  • Dihydroxycholecalciferols
  • Hydroxycholecalciferols
  • Receptors, Calcitriol
  • Receptors, Steroid
  • Vitamin D-Binding Protein
  • 23,25-dihydroxyvitamin D3
  • 23-keto-25-hydroxyvitamin D3
  • Calcifediol
  • Calcium