A novel strategy involved in [corrected] anti-oxidative defense: the conversion of NADH into NADPH by a metabolic network.
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.
Singh
Ranji
R
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
Lemire
Joseph
J
Mailloux
Ryan J
RJ
Appanna
Vasu D
VD
D000975:Antioxidants / Q000737:chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009243:NAD / Q000737:chemistry*; D009249:NADP / Q000737:chemistry*; D010071:Oxaloacetates / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011551:Pseudomonas fluorescens / Q000201:enzymology / Q000378:metabolism; D011770:Pyruvate Kinase / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000378:metabolism; D024483:Vitamin K 3 / Q000737:chemistry
D000975:Antioxidants; D010071:Oxaloacetates; D016877:Oxidants; D009243:NAD; D009249:NADP; D024483:Vitamin K 3; D011770:Pyruvate Kinase