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Glutamine metabolism and energy homeostasis during oxidative stress.

by Nohaiah Saeed Aldarini

Institution: Laurentian University
Year: 2017
Keywords: Glutamine synthetase; ATP production; Oxidative stress; Metabolic network
Posted: 02/01/2018
Record ID: 2154919
Full text PDF: https://zone.biblio.laurentian.ca/handle/10219/2745


Abstract

When living organisms are exposed to oxidative stress, they are known to devise intricatemechanisms to counter reactive oxygen species (ROS). It is well established that ROS lead to thereduction in the activity of numerous tricarboxylic acid (TCA) cycle enzymes and impede O2-dependent energy production. In this study we demonstrate an alternative metabolic pathway toadenosine triphosphate (ATP) synthesis when the microbe Pseudomonas fluorescens is challengedby H2O2.in a medium with glutamine as the sole source of carbon and nitrogen. Under oxidative stressthe microbe utilized glutamine synthease (GS) to release a constant supply of energy locked in theamide bond of glutamine. When grown in presence of H2O2, the level of GS was higher in the stressedcultures compared to the control. The up-regulation of phospho-transfer enzymes such as acetatekinase (ACK), adenylate kinase (AK), and nucleoside diphosphate kinase (NDPK) are involved inmaintaining ATP homeostasis in the oxidatively challenged cells. The increased amount of pyruvate phosphate dikinase (PPDK) and phosphoenol pyruvate carboxylase (PEPC) in stressed cells helpedfuel the synthesis of ATP. The enhanced activities of isocitrate dehydrogenase-NAD dependent(ICDH-NAD) and glutamate dehydrogenase (GDH) also provided intermediate metabolites forenergy generation. These metabolic reconfigurations may reveal crucial therapeutic tools against infectious microbes dependent on host glutamine for proliferation.

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