Abstract
The reduced nicotinamide adenine dinucleotide phosphate (NADPH) is pivotal to the cellular anti-oxidative defence strategies in most organisms. Although its production mediated by different enzyme systems has been relatively well-studied, metabolic networks dedicated to the biogenesis of NADPH have not been fully characterized. In this report, a metabolic pathway that promotes the conversion of reduced nicotinamide adenine dinucleotide (NADH), a pro-oxidant into NADPH has been uncovered in Pseudomonas fluorescens exposed to oxidative stress. Enzymes such as pyruvate carboxylase (PC), malic enzyme (ME), malate dehydrogenase (MDH), malate synthase (MS), and isocitrate lyase (ICL) that are involved in disparate metabolic modules, converged to create a metabolic network aimed at the transformation of NADH into NADPH. The downregulation of phosphoenol carboxykinase (PEPCK) and the upregulation of pyruvate kinase (PK) ensured that this metabolic cycle fixed NADH into NADPH to combat the oxidative stress triggered by the menadione insult. This is the first demonstration of a metabolic network invoked to generate NADPH from NADH, a process that may be very effective in combating oxidative stress as the increase of an anti-oxidant is coupled to the decrease of a pro-oxidant.
Highlights
nicotinamide adenine dinucleotide phosphate (NADPH) is an essential anabolic reducing agent in all living organisms and it is involved in a plethora of biochemical reactions
As part of our study to elucidate the various stratagems organisms deploy to live in an aerobic environment and to survive oxidative stress, we have identified an intriguing metabolic pathway dedicated to the production of NADPH
This data is consistent with our previous observations that P. fluorescens treated with menadione manipulates the levels of NADH and NADPH in an effort combat oxidative stress [10]
Summary
NADPH is an essential anabolic reducing agent in all living organisms and it is involved in a plethora of biochemical reactions. NADPH is vital in anti-oxidative defense mechanisms as it is the universal reducing power fuelling the activities of such enzymes as catalase, superoxide dismutase, and glutathione peroxidase [1]. These proteins play a crucial role in allowing organisms to thrive in an aerobic environment. The biogenesis of DNA is another important function mediated by NADPH in all organisms. Owing to its involvement in a multitude of functions, NADPH is undoubtedly a very critical molecule in all living organisms
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