THE EFFECTS OF ANTICONVULSANT DRUGS ON VITAMIN-D3-ACTIVATING CYTOCHROME-P-450-LINKED MONOOXYGENASE SYSTEMS

被引：23

作者：

TOMITA, S ^{[1
]}

OHNISHI, J ^{[1
]}

NAKANO, M ^{[1
]}

ICHIKAWA, Y ^{[1
]}

机构：

[1] UNIV HOSP KAGAWA,KAGAWA MED SCH,FAC MED,DEPT BIOCHEM,DIV PHARM,MIKI CHO,KAGAWA 76107,JAPAN

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 1991年 / 39卷 / 04期

关键词：

D O I：

10.1016/0960-0760(91)90241-V

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The effects of two anticonvulsant drugs, phenytoin and sodium valproate, on the bioactivation of vitamin D3 have been studied with respect to the microsomal and mitochondrial cytochrome P-450-linked monooxygenase systems that contribute to 25-hydroxylation of vitamin D3 in rabbit liver, and the mitochondrial cytochrome P-450-linked monooxygenase system that catalyzes 1-alpha-hydroxylation of 25-hydroxyvitamin D3 in rabbit kidney. These anticonvulsant drugs were found to inhibit the 25-hydroxylase activity on vitamin D3 in liver microsomes and mitochondria, respectively, but not to inhibit the 1-alpha-hydroxylation of 25-hydroxyvitamin D3, even over a wide concentration range. Moreover, the activities of the components of the cytochrome P-450-linked monooxygenase systems: NADPH-cytochrome P-450 reductase, NADPH-ferredoxin reductase and ferredoxin, were never inhibited by these drugs. It is possible that the inhibition of bioactivation of vitamin D3 by these anticonvulsant drugs causes rickets and osteomalacia, and the site of inhibition is expected to be the cytochrome P-450 mediated reactions in liver mitochondria.

引用

页码：479 / 485

页数：7

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