识别的CYP3A7格列本脲在人类胎儿肝脏代谢。
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普拉萨德•舒斯特DL Risler LJ, B, Calamia JC, Voellinger杰,凯莉EJ, Unadkat JD,赫伯特MF,沈DD, Thummel KE,毛泽东问
识别的CYP3A7格列本脲在人类胎儿肝脏代谢。
生物化学杂志。2014年12月15日,92 (4):690 - 700。doi: 10.1016 / j.bcp.2014.09.025。Epub 2014年10月22日。
- PubMed ID
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25450675 (在PubMed]
- 文摘
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格列本脲是常用的治疗妊娠糖尿病;然而,胎儿暴露于格列本脲的原因还不是很清楚,可能短期和长期影响的健康的孩子。格列本脲可以穿过胎盘;足月胎儿浓度几乎是与母亲的水平。格列本脲是否胎儿代谢和通过什么机制尚未确定。在这项研究中,我们确定了动力学参数为格列本脲损耗CYP3A同功酶;格列本脲代谢特征由人类胎儿肝组织收集在怀孕的第一个或第二个三个月;和确定了主要负责格列本脲酶在人类胎儿肝脏代谢。对格列本脲CYP3A4代谢能力最高,其次是CYP3A7和CYP3A5(克林特·u = 37.1, 13.0,和8.7毫升/分钟/ nmol P450,分别)。M5是生成的主要代谢物CYP3A7和人类胎儿肝微粒体(HFLMs)大约96%的相对丰度。 M5 was also the dominant metabolite generated by CYP3A4, CYP3A5, and adult liver microsomes; however, M1-M4 were also present, with up to 15% relative abundance. CYP3A7 protein levels in HFLMs were highly correlated with glyburide Clint, 16alpha-OH DHEA formation, and 4'-OH midazolam formation. Likewise, glyburide Clint was highly correlated with 16alpha-OH DHEA formation. Fetal demographics as well as CYP3A5 and CYP3A7 genotype did not alter CYP3A7 protein levels or glyburide Clint. These results indicate that human fetal livers metabolize glyburide predominantly to M5 and that CYP3A7 is the major enzyme responsible for glyburide metabolism in human fetal livers.
