https://www.cell.com/cell/pdf/S0092-8674(03)00929-2.pdf

TSC2 mediates cellular energy response to control cell growth and survival.

AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism

The SNF1/AMP-activated protein kinase (AMPK) family maintains the balance between ATP production and consumption in all eukaryotic cells. The kinases are heterotrimers that comprise a catalytic subunit and regulatory subunits that sense cellular energy levels. When energy status is compromised, the system activates catabolic pathways and switches off protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. Surprisingly, recent results indicate that the AMPK system is also important in functions that go beyond the regulation of energy homeostasis, such as the maintenance of cell polarity in epithelial cells.

AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.

Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ hete...

http://www.digestivo.fmed.edu.uy/Materiales/AMP%20kinasa.pdf

AMPK in Health and Disease

Activation of AMP-Activated Protein Kinase Leads to the Phosphorylation of Elongation Factor 2 and an Inhibition of Protein Synthesis

Several amino acids were found to stimulate glycogen synthesis and lipogenesis, and to inhibit ketogenesis in isolated rat hepatocytes. When hepatocytes were incubated in the presence of 20 mM-glucose, the amino acids could be classified in decreasing order of efficiency as follows: glutamine and proline, alanine, aminoisobutyric acid, asparagine and histidine for stimulation of glycogen synthesis; glutamine, proline and alanine for stimulation of lipogenesis; proline and glutamine for inhibition of ketogenesis. The study of the time course revealed that the rates were not linear and were preceded by a lag period. In all conditions studied, glutamine and proline were found to have similar quantitative effects on glycogen synthesis and lipid metabolism. However, their effects differ qualitatively. Indeed, the effects of proline on glycogen synthesis, lipogenesis and glutamate and aspartate content were faster. Moreover, proline increased the hydroxybutyrate/acetoacetate ratio, whereas glutamine did not change it. Incubation of hepatocytes with aminoisobutyric acid or under hypo-osmotic conditions, which increased cell volume and mimicked the amino acid-induced stimulation of glycogen synthesis, had little effect on lipogenesis. In hepatocytes incubated without glucose, ketogenesis was inhibited, in decreasing order of efficiency, by alanine, asparagine, glutamine and proline. Under these conditions, glutamine increased, alanine decreased and asparagine did not affect the concentration of malonyl-CoA. This indicates that the latter cannot be responsible for the inhibition of ketogenesis by alanine and asparagine.

Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes.

Liver swelling caused by incubating hepatocytes in hypotonic media or with amino acids that are co-transported with sodium ion stimulates glycogen synthesis and lipogenesis, and inhibits proteolysis. Thus, liver swelling can be regarded as an anabolic signal. The signal transduction for glycogen synthesis and lipogenesis involves changes in ionic composition of the cells that follow cell swelling, and leads to the activation of glycogen synthase and acetyl-CoA carboxylase, the rate-controlling enzymes in these pathways. The ionic changes result from the accumulation of metabolites of amino acids and from the cellular response to swelling which causes the extrusion of KCl. These ionic changes stimulate the protein phosphatase(s) responsible for the activation of glycogen synthase and acetyl-CoA carboxylase.

[Regulation of Liver-metabolism By Cell Swelling]

Our interest in the mechanics of swelling is recent and has arisen quite unexpectedly from the study of the control of glycogen metabolism in liver. Serendipity brought us to this promising field which we have explored and are still discovering with the zeal of a novice. This chapter summarizes our path from glycogen metabolism to cell swelling

A. Lavoinne

Papers

Activation of AMP-Activated Protein Kinase Leads to the Phosphorylation of Elongation Factor 2 and an Inhibition of Protein Synthesis

Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes.

[Regulation of Liver-metabolism By Cell Swelling]

From Glycogen Metabolism to Cell Swelling