Glutamine metabolism and energy homeostasis during oxidative stress.

Abstract

When living organisms are exposed to oxidative stress, they are known to devise intricate mechanisms to counter reactive oxygen species (ROS). It is well established that ROS lead to the reduction 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 to adenosine triphosphate (ATP) synthesis when the microbe Pseudomonas fluorescens is challenged by H2O2.in a medium with glutamine as the sole source of carbon and nitrogen. Under oxidative stress the microbe utilized glutamine synthease (GS) to release a constant supply of energy locked in the amide bond of glutamine. When grown in presence of H2O2, the level of GS was higher in the stressed cultures compared to the control. The up-regulation of phospho-transfer enzymes such as acetate kinase (ACK), adenylate kinase (AK), and nucleoside diphosphate kinase (NDPK) are involved in maintaining ATP homeostasis in the oxidatively challenged cells. The increased amount of pyruvate phosphate dikinase (PPDK) and phosphoenol pyruvate carboxylase (PEPC) in stressed cells helped fuel the synthesis of ATP. The enhanced activities of isocitrate dehydrogenase-NAD dependent (ICDH-NAD) and glutamate dehydrogenase (GDH) also provided intermediate metabolites for energy generation. These metabolic reconfigurations may reveal crucial therapeutic tools against infectious microbes dependent on host glutamine for proliferation.