23-Keto-25-hydroxyvitamin D3: a vitamin D3 metabolite with high affinity for the 1,25-dihydroxyvitamin D specific cytosol receptor.
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.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002112:Calcifediol / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D003600:Cytosol / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D006887:Hydroxycholecalciferols / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008968:Molecular Conformation; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014809:Vitamin D-Binding Protein
D002352:Carrier Proteins; D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014809:Vitamin D-Binding Protein; C031699:23,25-dihydroxyvitamin D3; C036023:23-keto-25-hydroxyvitamin D3; D002112:Calcifediol; D002118:Calcium