ArticleAntioxidants & redox signaling2015
Inability to maintain GSH pool in G6PD-deficient red cells causes futile AMPK activation and irreversible metabolic disturbance.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 70 citations in OpenAlex.
- Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion.The Journal of clinical investigation · 2020Trial
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- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Trans-Zeatin EnhancesMicroorganisms · 2025Article
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- Alzheimer's Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and l-Cysteine Supplementation.Antioxidants & redox signaling · 2024Review
- The RoxyScan is a novel measurement of red blood cell deformability under oxidative and shear stress.Scientific reports · 2024Article
- Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion.Cell cycle (Georgetown, Tex.) · 2023Article
- Oxidative Stress in Healthy and Pathological Red Blood Cells.Biomolecules · 2023Review
- Surprising Structural and Functional Properties of Favism Erythrocytes Are Linked to Special Metabolic Regulation: A Cell Aging Study.International journal of molecular sciences · 2022Article
- N-Acetylcysteine protects against cobalt chloride-induced endothelial dysfunction by enhancing glucose-6-phosphate dehydrogenase activity.FEBS open bio · 2022Article
- The Metabolic Landscape in Osteoarthritis.Aging and disease · 2022Article
- Article
- Interference With Redox Homeostasis Through a G6PD-Targeting Self-Assembled Hydrogel for the Enhancement of Sonodynamic Therapy in Breast Cancer.Frontiers in chemistry · 2022Article
- Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation.Frontiers in nutrition · 2022Review
- Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants.BioMedicine · 2022Article
- Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma.Frontiers in pharmacology · 2022Article
- Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives.Trends in pharmacological sciences · 2021Review
- Hematologic and systemic metabolic alterations due to Mediterranean class II G6PD deficiency in mice.JCI insight · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsGlucose 6-phosphate dehydrogenase (G6PD) is essential for maintenance of nicotinamide dinucleotide hydrogen phosphate (NADPH) levels and redox homeostasis. A number of drugs, such as antimalarial drugs, act to induce reactive oxygen species and hemolytic crisis in G6PD-deficient patients. We used diamide (DIA) to mimic drug-induced oxidative stress and studied how these drugs affect cellular metabolism using a metabolomic approach.
resultsThere are a few differences in metabolome between red blood cells (RBCs) from normal and G6PD-deficient individuals. DIA causes modest changes in normal RBC metabolism. In contrast, there are significant changes in various biochemical pathways, namely glutathione (GSH) metabolism, purine metabolism, and glycolysis, in G6PD-deficient cells. GSH depletion is concomitant with a shift in energy metabolism. Adenosine monophosphate (AMP) and adenosine diphosphate (ADP) accumulation activates AMP protein kinase (AMPK) and increases entry of glucose into glycolysis. However, inhibition of pyruvate kinase (PK) reduces the efficacy of energy production. Metabolic changes and protein oxidation occurs to a greater extent in G6PD-deficient RBCs than in normal cells, leading to severe irreversible loss of deformability of the former. INNOVATION AND
conclusionNormal and G6PD-deficient RBCs differ in their responses to oxidants. Normal cells have adequate NADPH regeneration for maintenance of GSH pool. In contrast, G6PD-deficient cells are unable to regenerate enough NADPH under a stressful situation, and switch to biosynthetic pathway for GSH supply. Rapid GSH exhaustion causes energy crisis and futile AMPK activation. Our findings suggest that drug-induced oxidative stress differentially affects metabolism and metabolite signaling in normal and G6PD-deficient cells. It also provides an insight into the pathophysiology of acute hemolytic anemia in G6PD-deficient patients.
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