title: The role of glutamine synthetase in energy production and glutamine metabolism during oxidative stress.
abstract: Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls. The enhanced activities of such enzymes as acetate kinase, adenylate kinase and nucleotide diphosphate kinase ensured the efficacy of this ATP producing-machine by transferring the high energy phosphate. The elevated amounts of phosphoenol pyruvate carboxylase and pyruvate orthophosphate dikinase recorded in the H2O2exposed cells provided another route to ATP independent of the reduction of O2. This is the first demonstration of a metabolic pathway involving GS dedicated to ATP synthesis. The phospho-transfer network that is pivotal to the survival of the microorganism under oxidative stress may reveal therapeutic targets against infectious microbes reliant on glutamine for their proliferation.
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.
authors.forename: Nohaiah
authors.initials: N
authors.lastname: Aldarini
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.
authors.forename: Azhar A
authors.initials: AA
authors.lastname: Alhasawi
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Thomas
authors.affiliation: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada. vappanna@laurentian.ca.
authors.forename: Vasu D
authors.initials: VD
authors.lastname: Appanna
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D003470:Culture Media / Q000737:chemistry; D004734:Energy Metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D011551:Pseudomonas fluorescens / Q000187:drug effects / Q000502:physiology*
chemical_list: D003470:Culture Media; D016877:Oxidants; D005973:Glutamine; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D005974:Glutamate-Ammonia Ligase
keywords: ATP budget; Glutamine synthetase; Metabolic networks; Oxidative stress