7-ethoxycoumarin O-deethylation in perfused livers from ethanol-fed rats: evidence for an important role of mitochondrial reducing equivalents.
7-ethoxycoumarin O-deethylation in perfused livers from ethanol-fed rats: evidence for an important role of mitochondrial reducing equivalents.
复制标题
乙醇喂养大鼠灌注肝脏中的 7-乙氧基香豆素 O-去乙基化：线粒体还原当量的重要作用的证据。
DOI：
10.1159/000138266
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发表时间：
1987
期刊：
影响因子：
3.1
通讯作者：
Sweeny,DJ
中科院分区：
文献类型：
--
作者：
Reinke,LA;Tupper,JS;Sweeny,DJ
7-乙氧基香豆素（7 EC）O-脱乙基化在灌注肝脏的速率增加约3倍，慢性乙醇喂养。急性添加乙醇（5 mM）和抗霉素A（0.03 mM）强烈抑制7 EC代谢灌注肝脏从乙醇喂养的大鼠，但较少的抑制作用时，观察到这些药物被添加到微粒体或灌注肝脏从对照组大鼠。通过比较输注1- 14 C-葡萄糖或6- 14 C-葡萄糖期间14 CO2的释放来评估灌注肝脏中肝脏磷酸戊糖循环的活性。7 EC输注导致对照大鼠肝脏中1- 14 C-葡萄糖产生的14 CO2比乙醇喂养大鼠肝脏中的14 CO2产生增加3倍，表明对照大鼠肝脏中的戊糖循环活性更高。因此，7 EC代谢的显著抑制所造成的乙醇和抗霉素A的输液可以解释由一个更大的依赖于线粒体来源的NADPH在乙醇喂养的大鼠的肝脏。二硝基苯酚（0.05 mM）不抑制灌注肝脏中的7 EC代谢，表明抗霉素A产生的抑制机制涉及细胞氧化还原状态的降低，而不是能量的减少。
Rates of 7-ethoxycoumarin (7EC) O-deethylation in perfused livers were increased approximately 3-fold by chronic ethanol feeding. The acute addition of ethanol (5 mM) and antimycin A (0.03 mM) strongly inhibited 7EC metabolism in perfused livers from ethanol-fed rats, but less inhibition was observed when these agents were added to microsomes or to perfused livers from control rats. The activity of the hepatic pentose phosphate cycle in perfused livers was assessed by comparing14CO2release during the infusion of 1-14C-glucose or 6-14C-glucose. 7EC infusion caused a 3-fold greater increase in14CO2production from 1-14C-glucose in a liver from a control rat than in a liver from an ethanol-fed rat, indicating greater hepatic pentose cycle activity in livers of control rats. Thus, the pronounced inhibition of 7EC metabolism caused by infusion of ethanol and antimycin A may be explained by a greater dependency on mitochondrial sources of NADPH in livers of ethanol-fed rats. Dinitrophenol (0.05 mM) did not inhibit 7EC metabolism in perfused livers, indicating that a reduction in the cellular redox state, and not diminished energetics, is involved in the mechanism of inhibition produced by antimycin A.