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How nutrients, energy state, and hormones reprogram metabolism : transcriptional regulators controlled by the LKB1/AMPK pathway

Abstract

One of the fundamental requirements of all cells is to maintain cellular energy balance between ATP consumed by cellular processes and ATP generated. For dividing eukaryotic cells, nutrient availability couples tightly with ATP generation, and cells must have nutrient and energy sensors to monitor intracellular stores and maintain energy homeostasis. One of the major regulators of cellular and organismal energy homeostasis is the AMP- activated protein kinase (AMPK), which is activated under conditions when intracellular ATP levels drop. AMPK plays critical roles in regulating growth and reprogramming metabolism through direct phosphorylation of downstream substrates involved in many biosynthetic pathways, as well as phosphorylating transcriptional regulators that can reprogram cells to better fit their metabolic demands. We examine here how AMPK and its related kinases regulate metabolism in the liver by directly phosphorylating key critical transcriptional regulators such as the Class IIa HDACs, SREBP transcription factors, the HAT p300 and others to control lipogenesis, gluconeogenesis and other key metabolic pathways

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