C(24)- and C(23)-oxidation, converging pathways of intestinal 1,25-dihydroxyvitamin D3 metabolism: identification of 24-keto-1,23,25-trihydroxyvitamin D3

Biochemistry. 1983 Dec 6;22(25):5848-53. doi: 10.1021/bi00294a025.

Abstract

24-Keto-1,23,25-trihydroxyvitamin D3 has been identified as a major 1,25-dihydroxyvitamin D3 metabolite, produced by intestinal mucosa cells isolated from rats dosed chronically with 1,25-dihydroxyvitamin D3. The identification was based on ultraviolet absorbance spectroscopy, mass spectroscopy, and chemical derivatization. The pathway of biosynthesis proceeded through 1,24,25-trihydroxyvitamin D3 and 24-keto-1,25-dihydroxyvitamin D3, which are physiological metabolites of 1,25-dihydroxyvitamin D3. Previous work [Napoli, J. L., Pramanik, B. C., Royal, P. M., Reinhardt, T. A., & Horst, R. L. (1983) J. Biol. Chem. 258, 9100-9107] had shown that the amount of 24-keto-1,23,25-trihydroxyvitamin D3 in intestine in vivo, relative to its C(24)-oxidized precursors, is enhanced by chronically dosing rats with 1,25-dihydroxyvitamin D3. These results establish the C(24)-oxidation pathway as a predominant route of intestinal 1,25-dihydroxyvitamin D3 metabolism under physiological conditions and indicate that treatment of the rat with exogenous 1,25-dihydroxyvitamin D3 causes expression of C(23)-hydroxylase activity, which uses C(24)-oxidized 1,25-dihydroxyvitamin D3 metabolites as substrates.

Publication types

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

MeSH terms

  • Animals
  • Calcitriol / analogs & derivatives*
  • Calcitriol / metabolism*
  • Intestinal Mucosa / metabolism*
  • Male
  • Mass Spectrometry
  • Rats
  • Rats, Inbred Strains
  • Spectrophotometry, Ultraviolet

Substances

  • 24-keto-1,23,25-trihydroxyvitamin D3
  • Calcitriol