Systems biology of the metabolic network regulated by the Akt pathway |
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| Authors: | Mosca Ettore Barcella Matteo Alfieri Roberta Bevilacqua Annamaria Canti Gianfranco Milanesi Luciano |
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| Affiliation: | Institute for Biomedical Technologies, CNR, Segrate, Italy. ettore.mosca@itb.cnr.it |
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| Abstract: | Cancer has been proposed as an example of systems biology disease or network disease. Accordingly, tumor cells differ from their normal counterparts more in terms of intracellular network dynamics than single markers. Here we shall focus on a recently recognized hallmark of cancer, the deregulation of cellular energetics. The constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been confirmed as an essential step toward cell transformation. We will consider how the effects of Akt activation are connected with cell metabolism; more precisely, we will review existing metabolic models and discuss the current knowledge available to construct a kinetic model of the most relevant metabolic processes regulated by the PI3K/Akt pathway. The model will enable a systems biology approach to predict the metabolic targets that may inhibit cell growth under hyper activation of Akt. |
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| Keywords: | ACC, acetyl-CoA carboxylase ACCOA, acetyl-CoA ACD, acyl-CoA dehydrogenase ACL, ATP citrate lyase ACS, acyl-CoA synthetase ADP, adenosine diphosphate ALD, fructose 1,6 bisphosphate aldolase AMP, adenosine monophosphate ATP, adenosine triphosphate BPG, 1,3-bisphosphoglycerate CAC, carnitine acyl-carnitine carrier CIT, citrate COA, coenzyme A CPT1A, carnitine palmitoyltransferase 1A CPT II, carnitine palmitoyltransferase II DE, differential equation DHAP, dihydroxyacetone phosphate ECH, enoyl-CoA hydratase EG, extended glycolysis, ENO, enolase EP, phosphoribulose epimerase E4P, erythrose-4-phosphate FA, fatty acid FASN, fatty acid synthase F16BP, fructose-1,6-bisphosphate F26BP, fructose 2,6-bisphosphate F6P, fructose-6-phosphate GAP, glyceraldehyde-3-phosphate GMM, glutamine mithocondrial metabolism G6PD, glucose-6-phosphate dehydrogenase GAPDH, glyceraldehyde-3-phosphate dehydrogenase GLC, glucose GLUT, glucose transporter GDH, glutamate dehydrogenase GLS, glutaminase G6P, glucose-6-phosphate HCD, 3-Hydroxyacyl CoA Dehydrogenases HK, hexokinase HPI, hexose-6-phosphate isomerase KI, Ribose phosphate isomerase LAC, lactic acid LDH, lactate dehydrogenase MALCOA, malonyl-CoA MCA, metabolic control analysis MPM, mitochondrial pyruvate metabolism NAD, nicotinamide adenine dinucleotides NADH, nicotinamide adenine dinucleotides OCT, 3-oxoacyl-CoA thiolase PDC, pyruvate dehydrogenase complex PEP, phosphoenolpyruvate PFK-1, phosphofructokinase type 1 PFK-2, phosphofructokinase type 2 6PG, 6-phosphogluconate 2PGA, 2-phosphoglycerate 3PGA, 3-phosphoglycerate PGAM, 3-phosphoglycerate mutase 6PGD, phosphogluconate dehydrogenase PGK, phosphoglycerate kinase Pi, inorganic phosphate PI3K, phosphatidylinositol 3-kinase PYC, pyruvate carrier PYK, pyruvate kinase PYR, pyruvate PYRt, pyruvate diffusion between cytosol and mitochondrial intermembrane space PRPP, phosphoribosyl-pyrophosphate PRPPS, phosphoribosyl-pyrophosphate synthetase R5P, ribose-5-phosphate Ru5P, ribulose-5-phosphate S7P, sedoheptulose-7-phosphate SA, sensitivity analysis TA, transaldolase TCA, tricarboxylic acid TK1, transketolase 1 TK2, transketolase 2 TPI, triosephosphate isomerase X5P, xylulose-5-phosphate |
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