Rat CYP24 catalyses 23S-hydroxylation of 26,26,26,27,27,27-hexafluorocalcitriol in vitro

被引：12

作者：

Hayashi, K ^{[1
]}

Akiyoshi-Shibata, M ^{[1
]}

Sakaki, T ^{[1
]}

Yabusaki, Y ^{[1
]}

机构：

[1] Sumitomo Chem Co Ltd, Biotechnol Lab, Takarazuka, Hyogo 6650051, Japan

来源：

XENOBIOTICA | 1998年 / 28卷 / 05期

关键词：

D O I：

10.1080/004982598239380

中图分类号：

R9 [药学];

学科分类号：

1007 ;

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.

引用

页码：457 / 463

页数：7

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