title: Redox control of glutamine utilization in cancer.
abstract: Glutamine utilization promotes enhanced growth of cancer cells. We propose a new concept map of cancer metabolism in which mitochondrial NADH and NADPH, in the presence of a dysfunctional electron transfer chain, promote reductive carboxylation from glutamine. We also discuss why nicotinamide nucleotide transhydrogenase (NNT) is required in vivo for glutamine utilization by reductive carboxylation. Moreover, NADPH, generated by both the pentose phosphate pathway and the cancer-specific serine glycolytic diversion, appears to sustain glutamine utilization for amino-acid synthesis, lipid synthesis, and for ROS quenching. The fact that the supply of NAD(+) precursors reduces tumor aggressiveness suggests experimental approaches to clarify the role of the NADH-driven redox network in cancer.
authors.affiliation: 1] SYSBIO Center for Systems Biology, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan and Rome, Italy [2] Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Alberghina
authors.affiliation: 1] SYSBIO Center for Systems Biology, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan and Rome, Italy [2] Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Via F.lli Cervi 93, Segrate, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Gaglio
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009243:NAD / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D061087:NADP Transhydrogenase, AB-Specific / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D008055:Lipids; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D005973:Glutamine; D009243:NAD; D009249:NADP; D061087:NADP Transhydrogenase, AB-Specific; C556045:NNT protein, human