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学科主题: 物理化学
题名: Ergosterol promotes the atypical kinetics of cytochrome P450 reductase and cytochrome P450-3A4 in recombinant yeast system
作者: Cheng J(程婕) ;  Liu Y(刘勇) ;  Yang L(杨凌)
会议名称: 第三届中日双边药理学和临床药理学会议
会议日期: 2007-8-23
出版日期: 2007-08-23
会议地点: 中国
通讯作者: 杨凌
部门归属: 十八室
主办者: 中国药理学会
摘要: Atypical kinetics of cytochrome P450 enzyme confounds the accurate prediction of drug metabolism from in vitro to in vivo in cDNA-expressed system. Microsomal membrane is reported to be a potential factor to modulate the cytochrome P450 (CYP) kinetics in P450 catalytic cycle. In the present study, we examined the effects of microsomal membrane on CPR and CYP3A4 kinetics in Saccharomyces cerevisiae BWG-CPR/3A4. METHODS Glycerol concentrations were mediated from 0%, 5%, 10%, 15% to 20% in yeast culture. The protein amounts, CYP contents, lipid phosphorus contents, ergosterol contents and CPR/CYP3A4 kinetics were measured. The data was further concluded by t test and correlative analysis. RESULTS The protein amounts, CYP contents and lipid phosphorus contents were no statistically differentiated; however, ergosterol contents and CPR/CYP3A4 kinetics was significantly different, and CPR/CYP3A4 kinetics correlated with ergosterol contents. The relationships between ergosterol in ER and enzymes atypical kinetics were followed subsequently to be ergosterol-CPR (r2=0.958), CPR-CYP3A4 (r2=0.892) and ergosterol-CYP3A4 (r2=0.759). CONCLUSION These correlative observations suggested that ergosterol potentially influenced the kinetic characters of CYP and CPR in recombinant system. Atypical kinetics of CPR and CYP should be noted to be implicated in the effect of microsomal membrane in cDNA-expressed systems. Key words: Saccharomyces cerevisiae, microsomal membrane, cytochrome P450, cytochrome P450 reductase, kinetics
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/112712
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Cheng J,Liu Y,Yang L. Ergosterol promotes the atypical kinetics of cytochrome P450 reductase and cytochrome P450-3A4 in recombinant yeast system[C]. 见:第三届中日双边药理学和临床药理学会议. 中国. 2007-8-23.
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