In vitro inhibitor studies of vitamin D 25-hydroxylase in rat liver microsomes.
The ability of four vitamin D analogs to inhibit the liver microsomal vitamin D-25-hydroxylase was determined. 19-Hydroxy-10(S),19-dihydrovitamin D3,25-fluorovitamin D3, 3 beta-hydroxy-9,10-seco-5,7,10(19)-choletrien-24-oic acid dimethylamide and 25-aza-vitamin D3 were competitive inhibitors with apparent KI values of 44, 137, and 870 nM, and 6.4 microM, respectively. The values for the 19-hydroxy-10(S), 19-dihydrovitamin D3, 25-fluorovitamin D3, and 25-aza-vitamin D3 correspond well to other literature reports with respect to their relative in vivo inhibitory properties. 24-Oxovitamin D3 oxime also proved to be a potent inhibitor but a detailed analysis was prohibited by the lack of material. The 3 beta-hydroxy-9,10-seco-5,7,10(19)-choletrien-24-oic acid dimethylamide was also tested in vivo but had no antagonistic activity when provided at a 2000-fold excess over vitamin D3.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002762:Cholecalciferol / Q000494:pharmacology*; D053493:Cholestanetriol 26-Monooxygenase; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008954:Models, Biological; D051381:Rats; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*
D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase