Aldarini Nohaiah, Alhasawi Azhar A, Thomas Sean C, Appanna Vasu D
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.
Antonie Van Leeuwenhoek. 2017 May;110(5):629-639. doi: 10.1007/s10482-017-0829-3. Epub 2017 Jan 17.
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 HO, 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 HO exposed cells provided another route to ATP independent of the reduction of O. 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.
已知氧化应激会严重阻碍有氧三磷酸腺苷（ATP）的合成。然而，代谢功能多样的荧光假单胞菌通过启动替代的ATP生成网络来应对这一挑战。当在含有谷氨酰胺作为唯一有机养分的培养基中、在过氧化氢（HO）存在的情况下生长时，这种微生物利用谷氨酰胺合成酶（GS）来调节其能量收支。与对照相比，在应激细胞中，这种介导谷氨酰胺中储存能量释放的酶的活性急剧增加。诸如乙酸激酶、腺苷酸激酶和核苷二磷酸激酶等酶活性的增强，通过转移高能磷酸基团确保了这个ATP产生机制的功效。在暴露于过氧化氢的细胞中记录到的磷酸烯醇式丙酮酸羧化酶和磷酸丙酮酸二激酶数量的增加，提供了另一条不依赖于氧气还原的ATP生成途径。这是首次证明涉及GS的代谢途径专门用于ATP合成。在氧化应激下对微生物生存至关重要的磷酸转移网络，可能揭示针对依赖谷氨酰胺进行增殖的感染性微生物的治疗靶点。
