细菌内毒素对大鼠肝细胞糖异生作用的抑制特性及部位。磷酸果糖激酶-1的激活。
The characteristics and site of inhibition of gluconeogenesis in rat liver cells by bacterial endotoxin. Stimulation of phosphofructokinase-1.
作者信息
Knowles R G, McCabe J P, Beevers S J, Pogson C I
出版信息
Biochem J. 1987 Mar 15;242(3):721-8. doi: 10.1042/bj2420721.
Abstract
The characteristics and site of inhibition of gluconeogenesis by endotoxin were investigated in liver cells isolated from control and endotoxin-treated rats. Endotoxin treatment was associated with inhibition (40-50%) of gluconeogenesis from lactate plus pyruvate over a range of concentrations of substrate and of oleate and with or without glucose or glucagon. Similar inhibition was observed with asparagine, proline, glutamine, alanine and a substrate mixture, but not with glycerol, glyceraldehyde, dihydroxyacetone or endogenous substrates. There was no change in cellular ATP content or in the rates of ketogenesis or ureogenesis from asparagine, proline or glutamine. Other effects on isotopic fluxes, metabolite contents, enzyme activities and control coefficients were consistent with the suggestion that the effects of endotoxin on gluconeogenesis are exerted at the level of phosphofructokinase-1, and not at phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate carboxylase or glucokinase.
摘要
在内毒素处理组大鼠和对照组大鼠分离出的肝细胞中，研究了内毒素对糖异生作用的抑制特性和抑制位点。在内毒素处理组中，无论有无葡萄糖或胰高血糖素存在，在一系列底物浓度以及油酸浓度下，乳酸加丙酮酸的糖异生作用均受到抑制（40%-50%）。使用天冬酰胺、脯氨酸、谷氨酰胺、丙氨酸和一种底物混合物时也观察到类似的抑制作用，但使用甘油、甘油醛、二羟基丙酮或内源性底物时未观察到抑制作用。细胞内ATP含量以及从天冬酰胺、脯氨酸或谷氨酰胺生成酮体或尿素的速率均未发生变化。对内毒素对同位素通量、代谢物含量、酶活性和控制系数的其他影响的研究结果表明，内毒素对糖异生作用的影响是在磷酸果糖激酶-1水平发挥的，而非在磷酸烯醇式丙酮酸羧激酶、丙酮酸激酶、丙酮酸羧化酶或葡萄糖激酶水平发挥的。
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