名称:
Rat CYP24 catalyses 23S-hydroxylation of 26,26,26,27,27,27-hexafluorocalcitriolin vitro
摘要:
1. Kidney mitochondrial 24-hydroxylase cytochrome P450 (CYP24) catalyses sequential hydroxylation at both C-24 and C-23 positions of calcidiol and calcitriol. Here, we have investigated the in vitro metabolism of a hexafluorinated derivative of calcitriol, 26,26,26,27,27,27-hexafluorocalcitriol (ST-630), in a reconstituted system by using recombinant Escherichia coli membrane fractions containing rat CYP24.2. When ST-630 was incubated with CYP24 supplemented with bovine adrenodoxin and NADPH-adrenodoxin reductase, a distinct metabolite could be observed. This metabolite was found to be 26,26,26,27,27,27-hexafluoro-23S-hydroxycalcitriol, a biologically active metabolite of ST-630, based on cochromatography on HPLC and mass spectrometric analysis.3. These results show the direct evidence that CYP24 plays an essential role in the metabolism of ST-630 to yield its 23S-hydroxylated metabolite, as observed in cultured cells and experimental animal studies.