The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline

›› 2009, Vol. 4 ›› Issue (2): 41-50.

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The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline

收稿日期:2008-01-19 修回日期:2008-12-22 出版日期:2009-04-20 发布日期:2009-04-20

The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline

Jun Wang; Li Yang; Changhong Wang; Zhengtao Wang *

Key Laboratory of Standardization of Chinese Medicines of the Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received:2008-01-19 Revised:2008-12-22 Online:2009-04-20 Published:2009-04-20
Contact: Zhengtao Wang

摘要/Abstract

Abstract: Pyrrolizidine alkaloids (PAs) are hepatotoxic to domestic livestock and carcinogenic to laboratory rodents. Previous in vitro metabolism studies have shown that (±) 6, 7-dihydro-7- hydroxyl-1-(hydroxymethy)-5H- pyrrolizine (DHP) and pyrrolizidine N-oxide are major metabolites of PAs. In this study, the metabolism of monocrotaline converted to its N-oxide in rat liver microsomes was investigated. The monocrotaline metabolite, monocrotaline N-oxide, was identified by MS² analysis. Based on an established HPLC quantification method, the metabolic kinetic parameters of the formation of monocrotaline N-oxide were calculated as K_m=566.9 μM and V_max=483.8±14.04 nmol·min^-1·mg^-1protein. Furthermore, the activities of cytochrome P-450 enzymes (CYP450) and flavin-containing monooxygenases (FMO) on the formation of monocrotaline N-oxide by in vitro metabolism were evaluated by well characterized chemical inhibitors, which provided evidence that CYP450 and FMO are the major enzymes responsible for N-oxide metabolite formation from monocrotaline.

Key words: pyrrolizidine alkaloid, monocrotaline, monocrotaline N-oxide, CYP 450, FMO

. The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline [J]. , 2009, 4(2): 41-50.

Jun Wang;Li Yang;Changhong Wang;Zhengtao Wang *. The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline [J]. , 2009, 4(2): 41-50.

亚洲传统医药

The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline

The action of cytochrome p450 enzymes and flavin-containing monooxygenases on the N-oxide of pyrrolizidine alkaloid monocrotaline

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