Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis

Abstract

Normal embryogenesis requires complex regulation and precision, which depends on multiple mechanistic details. Defective embryogenesis can occur by various mechanisms. Maintaining redox homeostasis is of importance during embryogenesis. NADPH, as produced from the action of glucose-6-phosphate dehydrogenase (G6PD), has an important role in redox homeostasis, serving as a cofactor for glutathione reductase in the recycling of glutathione from oxidized glutathione and for NADPH oxidases and nitric oxide synthases in the generation of reactive oxygen (ROS) and nitrogen species (RNS). Oxidative stress differentially influences cell fate and embryogenesis. While low levels of stress (eustress) by ROS and RNS promote cell growth and differentiation, supra-physiological concentrations of ROS and RNS can lead to cell demise and embryonic lethality. G6PD-deficient cells and organisms have been used as models in embryogenesis for determining the role of redox signaling in regulating cell proliferation, differentiation and migration. Embryogenesis is also modulated by anti-oxidant enzymes, transcription factors, microRNAs, growth factors and signaling pathways, which are dependent on redox regulation. Crosstalk among transcription factors, microRNAs and redox signaling is essential for embryogenesis.

ZmG6PDH1 in glucose-6-phosphate dehydrogenase family enhances cold stress tolerance in maize

“…G6PDHs have previously been shown to help maintain proper carbon flow and NADPH generation within the PPP ( Chen et al., 2022 ). NADPH redox status was initially analyzed to confirm the ability of cytosolic ZmGPDH1 to modulate the redox state within cells under cold stress conditions.…”

“…Glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) is a ubiquitously expressed enzyme responsible for catalyzing the rate-limiting first step of the pentose phosphate pathway (PPP) in which b-D-glucose-6-phosphate (G6P) is oxidized to 6-phosphoglucono-d-lactone and oxidized nicotinamide adenine dinucleotide phosphate (NADP + ) is reduced to yield NADPH ( Chen et al., 2022 ). NADPH, produced through PPP-mediated oxidation, functions as a reducing agent essential for redox homeostasis and lipid biosynthesis ( Esposito, 2016 ).…”

The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers

“…As the rate-limiting enzyme in the PPP, G6PD is responsible for the production of NADPH, a crucial cofactor for various anti-oxidant enzymes. These anti-oxidant enzymes-including superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase 4 (GPX4), thioredoxin (TRX), and reduced glutathione (GSH)-are essential for neutralizing RS such as ROS, RNS, and RSS [49]. NADPH, produced through the PPP, is integral to the function of these antioxidant enzymes [49,50].…”

An Overall View of the Functional and Structural Characterization of Glucose-6-Phosphate Dehydrogenase Variants in the Mexican Population

“…For the obtention of the cellular NADPH pool, G6PD catalyzes the oxidation of glucose-6-phosphate (G6P) to glucose-6-phosphogluconate with the concomitant production of one molecule of NADPH, which plays an essential role in redox homeostasis and is used in RBCs as a substrate for two enzymes: glutathione reductase (GR) and thioredoxin reductase (TR). These enzymes are crucial to defend against reactive oxygen species (ROS) [ 8 , 9 , 10 , 11 , 12 , 13 ]. G6PD-deficient RBCs possess decreased NADPH production and, therefore, altered cellular redox homeostasis and, ultimately, increased extravascular hemolysis, which is triggered by exogenous agents such as acute infections, drugs, or food.…”