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The Fate of Glutamine in Human Metabolism. The Interplay with Glucose in Proliferating Cells

IBGC CNRS UMR 5095 & Université de Bordeaux, 1, rue Camille Saint-Saëns, 33077 Bordeaux-CEDEX, France
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These authors contributed equally to this work.
Metabolites 2019, 9(5), 81; https://doi.org/10.3390/metabo9050081
Received: 22 February 2019 / Accepted: 23 April 2019 / Published: 26 April 2019
(This article belongs to the Special Issue Bioinformatics in Metabolomics)
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Abstract

Genome-scale models of metabolism (GEM) are used to study how metabolism varies in different physiological conditions. However, the great number of reactions involved in GEM makes it difficult to understand these variations. In order to have a more understandable tool, we developed a reduced metabolic model of central carbon and nitrogen metabolism, C2M2N with 77 reactions, 54 internal metabolites, and 3 compartments, taking into account the actual stoichiometry of the reactions, including the stoichiometric role of the cofactors and the irreversibility of some reactions. In order to model oxidative phosphorylation (OXPHOS) functioning, the proton gradient through the inner mitochondrial membrane is represented by two pseudometabolites DPH (∆pH) and DPSI (∆ψ). To illustrate the interest of such a reduced and quantitative model of metabolism in mammalian cells, we used flux balance analysis (FBA) to study all the possible fates of glutamine in metabolism. Our analysis shows that glutamine can supply carbon sources for cell energy production and can be used as carbon and nitrogen sources to synthesize essential metabolites. Finally, we studied the interplay between glucose and glutamine for the formation of cell biomass according to ammonia microenvironment. We then propose a quantitative analysis of the Warburg effect. View Full-Text
Keywords: model of central carbon and nitrogen metabolism; flux balance analysis; glutamine; warburg effect; hypoxia model of central carbon and nitrogen metabolism; flux balance analysis; glutamine; warburg effect; hypoxia
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Mazat, J.-P.; Ransac, S. The Fate of Glutamine in Human Metabolism. The Interplay with Glucose in Proliferating Cells. Metabolites 2019, 9, 81.

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