Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver
Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver
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DOI：
10.1016/j.cmet.2007.03.004
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发表时间：
2007-04-01
期刊：
影响因子：
29
通讯作者：
Magnuson, Mark A.
中科院分区：
文献类型：
--
作者：
Burgess, Shawn C.;He, TianTeng;Magnuson, Mark A.
当饮食中的碳水化合物不可用时，支持重要组织代谢所需的葡萄糖通过肝脏中的异生作用产生。磷酸烯醇式丙酮酸羧激酶（PEPCK）的表达通常被认为是肝脏新生的控制点，通常受循环激素的调节，以匹配全身葡萄糖需求。然而，这种调节在糖尿病中失败。由于其他分子和代谢因素也可以影响胚胎发生，因此PEPCK蛋白含量在胚胎发生控制中的明确作用尚不清楚。在这项研究中，在具有不同PEPCK蛋白含量的小鼠组中定量肝脏再生的代谢控制。令人惊讶的是，PEPCK含量降低90%的肝脏仅显示出类似于40%的致突变通量降低，表明PEPCK蛋白含量控制致突变的能力低于预期。然而，PEPCK通量与TCA循环活性密切相关，这表明在某些条件下，小鼠PEPCK表达必须与肝脏能量代谢协调，以控制肝脏异生。
When dietary carbohydrate is unavailable, glucose required to support metabolism in vital tissues is generated via gluconeogenesis in the liver. Expression of phosphoenolpyruvate carboxykinase (PEPCK), commonly considered the control point for liver gluconeogenesis, is normally regulated by circulating hormones to match systemic glucose demand. However, this regulation fails in diabetes. Because other molecular and metabolic factors can also influence gluconeogenesis, the explicit role of PEPCK protein content in the control of gluconeogenesis was unclear. In this study, metabolic control of liver gluconeogenesis was quantified in groups of mice with varying PEPCK protein content. Surprisingly, livers with a 90% reduction in PEPCK content showed only a similar to 40% reduction in gluconeogenic flux, indicating a lower than expected capacity for PEPCK protein content to control gluconeogenesis. However, PEPCK flux correlated tightly with TCA cycle activity, suggesting that under some conditions in mice, PEPCK expression must coordinate with hepatic energy metabolism to control gluconeogenesis.