Enzymes of glycolysis and the pentose phosphate pathway as targets of oxidants: Role of redox reactions on the carbohydrate catabolism

Redox reactions can modulate metabolic and signaling pathways with consequences on cellular adaptation to different stimuli. The abundance and structural features of some metabolic enzymes make these targets of oxidants, including one- and two-electron oxidant molecules, altering their structure and/or function. Therefore, redox processes play an important role in physiology and pathology. In particular, the oxidative post-translational modification of the enzymes that participate in glycolysis and the pentose phosphate pathway (PPP) can modulate the carbon flux affecting synthesis of nucleotides, as well as production of adenosine triphosphate (ATP) and reducing equivalents (in the form of nicotinamide adenine dinucleotide phosphate, NADPH). Specifically, generation of NADPH, a cofactor important for cell homeostasis, is key to the management of the redox status of cells towards oxidative insults. In this review we discuss the available literature on the impact of oxidative post-translational modifications on key glycolytic and PPP enzymes with an analysis of the consequences these may have for cell metabolic adaptation. We also discuss the contributions of new experimental and in silico approaches to the redox biochemistry field, which have significantly illuminated the intricate relationship between the pathways involved in carbohydrate metabolism and how these could be regulated by redox reactions. • Glycolysis and the pentose phosphate pathway (PPP) are critical routes of cells. • Metabolic enzymes are highly abundant in cells with GAPDH being one of the most abundant. • Oxidative modifications can modulate the biological function of metabolic enzymes. • Oxidation of human enzymes of glycolysis and the PPP has been partially investigated. • Oxidative inactivation of enzymes could affect the carbon-flux between glycolysis and PPP.