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首页> 外文期刊>The biochemical journal >Regulation of p-nitroanisole O-demethylation in perfused rat liver. Adenine nucleotide inhibition of NADP+-dependent dehydrogenases and NADPH-cytochrome c reductase
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Regulation of p-nitroanisole O-demethylation in perfused rat liver. Adenine nucleotide inhibition of NADP+-dependent dehydrogenases and NADPH-cytochrome c reductase

机译：灌注大鼠肝脏对硝基苯甲醚O-脱甲基化的调节。 NADP +依赖性脱氢酶和NADPH-细胞色谱酶的腺嘌呤核苷酸抑制作用

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pPerfusion of rat livers with 10 mM-fructose or pretreatment of the rat with 6-aminonicotinamide (70 mg/kg) 6 h before perfusion decreased intracellular ATP concentrations and increased the rate of p-nitroanisole O-demethylation. This increase was accompanied by a decrease in the free [NADP+]/[NADPH] ratio calculated from concentrations of substrates assumed to be in near-equilibrium with isocitrate dehydrogenase. After pretreatment with 6-aminonicotinamide the [NADP+]/[NADPH] ratio also declined. Reduction of NADP+ during mixed-function oxidation may be explained by inhibition of of one or more NADPH-generating enzymes. Glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase and “malic” enzyme, partially purified from livers of phenobarbital-treated rats, were inhibited by ATP and ADP. Inhibitor constants of ATP for the four dehydrogenases varied considerably, ranging from 9 micrometer for “malic” enzyme to 1.85 mM for glucose 6-phosphate dehydrogenase. NADPH-cytochrome c reductase was also inhibited by ATP (Ki 2.8 mM) and by ADP (Ki 0.9 mM), but not by AMP. Concentrations of ATP and ADP that inhibited glucose 6-phosphate dehydrogenase and the reductase were comparable with concentrations in the intact liver. Thus agents that lower intracellular ATP may accelerate rates of mixed-function oxidation by a concerted mechanism involving deinhibition of NADPH-cytochrome c reductase and one or more NADPH-generating enzymes./p
机译：>在灌注之前，用10mm果糖（70mg / kg）6小时，大鼠植入大鼠肝脏的灌注或预处理的大鼠的预处理降低细胞内ATP浓度并增加了对硝基吲哚O-去甲基化的速率。这种增加伴随着由诸如亚乙酸脱氢酶近平衡的基质浓度计算的自由[NADP +] / [NADPH]比率降低。在用6-氨基氨基酰胺预处理后，[NADP +] / [NADPH]比率也下降。可以通过抑制一种或多种产生的NADPH-生成酶来解释混合功能氧化期间的NADP +。葡萄糖6-磷酸脱氢酶，6-磷光葡萄糖脱氢酶，异柠檬酸脱氢酶和“苹果酸”酶，由ATP和ADP抑制了苯巴比妥处理的大鼠的肝脏纯化。对于四个脱氢酶的ATP抑制剂常数显着变化，从9微米为“苹果酸”酶至1.85mm的葡萄糖6-磷酸脱氢酶。 NADPH-细胞色素C还原酶也被ATP（ki 2.8mm）和ADP（ki 0.9mm）抑制，但不是通过放大器。抑制葡萄糖6-磷酸脱氢酶和还原酶的ATP和ADP的浓度与完整肝脏中的浓度相当。因此，降低细胞内ATP的试剂可以通过涉及抑制NADPH-细胞色素C还原酶和一种或多种NADPH-生成酶的齐节机制加速混合功能氧化率。

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