Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada.
Antonie Van Leeuwenhoek. 2011 Mar;99(3):433-42. doi: 10.1007/s10482-010-9538-x. Epub 2010 Dec 12.
Oxidative stress is an unavoidable peril that aerobic organisms have to confront. Thus, it is not surprising that intricate strategies are deployed in an effort to fend the dangers associated with living in an O(2) environment. In the classical models of anti-oxidative defense mechanisms, a variety of stratagems including the reactive oxygen species (ROS) scavenging systems, the NADPH-generating enzymes and the DNA repair machineries are highlighted. However, it is becoming increasingly clear that metabolism may be intimately involved in anti-oxidative defence. Recent data show that metabolic reprogramming plays a pivotal role in the survival of organisms exposed to oxidative stress. Here, we describe how Pseudomonas fluorescens, the metabolically-versatile soil microbe, manipulates its metabolic networks in an effort to counter oxidative stress. An intricate link between metabolism and anti-oxidative defense is presented. P. fluorescens reconfigures its metabolic processes in an effort to satisfy its need for NADPH during oxidative insult. Seemingly, disparate metabolic modules appear to partner together to concomitantly fine-tune the levels of the anti-oxidant NADPH and the pro-oxidant NADH. Central to this shift in the metabolic production of the pyridine nucleotides is the increase in NAD kinase with the concomitant decrease in NADP phosphatase. The tricarboxylic acid cycle is tweaked in an effort to limit the formation of NADH. This metabolic redox-balancing act appears to afford a potent tool against oxidative challenge and may be a more widespread ROS-combating tactic than hitherto recognized.
氧化应激是需氧生物必须面对的一种不可避免的危险。因此,毫不奇怪,人们会采用复杂的策略来抵御与在 O(2)环境中生存相关的危险。在抗氧化防御机制的经典模型中,强调了各种策略,包括活性氧 (ROS) 清除系统、NADPH 生成酶和 DNA 修复机制。然而,越来越明显的是,代谢可能与抗氧化防御密切相关。最近的数据表明,代谢重编程在暴露于氧化应激的生物体的存活中起着关键作用。在这里,我们描述了代谢灵活的土壤微生物荧光假单胞菌如何努力改变其代谢网络以对抗氧化应激。呈现了代谢与抗氧化防御之间的复杂联系。荧光假单胞菌重新配置其代谢过程,以在氧化损伤期间满足其对 NADPH 的需求。似乎不同的代谢模块似乎合作在一起,同时微调抗氧化剂 NADPH 和促氧化剂 NADH 的水平。这种吡啶核苷酸代谢产物变化的核心是 NAD 激酶的增加伴随着 NADP 磷酸酶的减少。三羧酸循环被调整以限制 NADH 的形成。这种代谢氧化还原平衡作用似乎提供了对抗氧化挑战的有力工具,并且可能是比迄今为止认识到的更广泛的 ROS 对抗策略。