Inhibition of mixed-function oxidation in perfused rat liver by fluoroacetate treatment.

Inhibition of mixed-function oxidation in perfused rat liver by fluoroacetate treatment.
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氟乙酸盐处理抑制灌注大鼠肝脏中的混合功能氧化。

DOI:
10.1016/0006-2952(84)90491-x
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发表时间:
1984
影响因子:
5.8
通讯作者:
Thurman,RG
Thurman,RG
中科院分区:
医学2区
文献类型:
--
作者:
Zhou,JL;Kauffman,FC;Ballow,CH;Thurman,RG

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研究了柠檬酸循环抑制剂氟乙酸盐对喂养大鼠离体灌注肝脏中对硝基苯甲醚混合功能氧化的影响。在肝脏灌注实验前3小时向大鼠注射5mg/kg氟乙酸钠,抑制柠檬酸循环。柠檬酸循环的抑制以柠檬酸盐的积累(5 倍)以及糖酵解和糖原分解的速率降低 50-90% 为标志。氟乙酸盐处理抑制灌注肝脏中的混合功能氧化约 50%,而不影响分离的微粒体对硝基苯甲醚 O-去甲基化。浓度高达 50 μM 的氟柠檬酸盐在体外不会抑制微粒体-硝基苯甲醚 O-去甲基化。这些数据支持这样的假设:完整肝细胞中的混合功能氧化依赖于通过柠檬酸循环产生的还原当量。
The effect of fluoroacetate, an inhibitor of the citric acid cycle, on the mixed-function oxidation ofp-nitroanisole in isolated perfused livers from fed rats was studied. The citric acid cycle was inhibited by injection of 5 mg/kg sodium fluoroacetate into rats 3 hr prior to liver perfusion experiments. Inhibition of the citric acid cycle was marked by accumulation of citrate (5-fold) and decreases in rates of glycolysis and glycogenolysis by 50–90%. Fluoroacetate treatment inhibited mixed function oxidation in the perfused liver by about 50% without affectingp-nitroanisole O-demethylation by isolated microsomes. Fluorocitrate, at concentrations up to 50 μM, did not inhibit microsomalp-nitroanisole O-demethylationin vitro. These data support the hypothesis that mixed-function oxidation in intact hepatocytes is dependent upon reducing equivalents generated via the citric acid cycle.