Metabolic defence against oxidative stress: the road less travelled so far

Abstract

Bacteria have survived, and many have thrived, since antiquity in the presence of the highly-reactive chalcogen—oxygen (O2). They are known to evoke intricate strategies to defend themselves from the reactive by-products of oxygen—reactive oxygen species (ROS). Many of these detoxifying mechanisms have been extensively characterized; superoxide dismutase, catalases, alkyl hydroperoxide reductase and the glutathione (GSH)-cycling system are responsible for neutralizing specific ROS. Meanwhile, a pool of NADPH—the reductive engine of many ROS-combating enzymes—is maintained by metabolic enzymes including, but not exclusively, glucose-6 phosphate dehydrogenase (G6PDH) and NADP-dependent isocitrate dehydrogenase (ICDH-NADP). So, it is not surprising that evidence continues to emerge demonstrating the pivotal role metabolism plays in mitigating ROS toxicity. Stemming from its ability to concurrently decrease the production of the pro-oxidative metabolite, NADH, while augmenting the antioxidative metabolite, NADPH, metabolism is the fulcrum of cellular redox potential. In this review, we will discuss the mounting evidence positioning metabolism and metabolic shifts observed during oxidative stress, as critical strategies microbes utilize to thrive in environments that are rife with ROS. The contribution of ketoacids—moieties capable of non-enzymatic decarboxylation in the presence of oxidants—as ROS scavengers will be elaborated alongside the metabolic pathways responsible for their homeostases. Further, the signalling role of the carboxylic acids generated following the ketoacid-mediated detoxification of the ROS will be commented on within the context of oxidative stress.