Glucose-6-Phosphate Dehydrogenase, NADPH, and Cell Survival

IUBMB Life - A Journal of the International Union of Biochemistry and Molecular Biology, 2012

649 citations recorded by the source corpus.

Glucose‐6‐phosphate dehydrogenase (G6PD) is the rate‐limiting enzyme of the pentose phosphate pathway. Many scientists think that the roles and regulation of G6PD in physiology and pathophysiology have been well established as the enzyme was first identified 80 years ago. And that G6PD has been extensively studied especially with respect to G6PD deficiency and its association with hemolysis, and with respect to the role G6PD plays in lipid metabolism. But there has been a growing understanding of the central importance of G6PD to cellular physiology as it is a major source of NADPH that is required by many essential cellular systems including the antioxidant pathways, nitric oxide synthase, NADPH oxidase, cytochrome p450 system, and others. Indeed G6PD is essential for cell survival. It has also become evident that G6PD is highly regulated by many signals that affect transcription, post‐translation, intracellular location, and interactions with other protein. Pathophysiologic roles for G6PD have also been identified in such disease processes as diabetes, aldosterone‐induced endothelial dysfunction, cancer, and others. It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes. In this review the biochemistry, regulatory signals, physiologic roles, and pathophysiologic roles for G6PD that have been elucidated over the past 20 years are discussed. 2012 IUBMB IUBMB Life, 2012

Subfields: Pathology and Forensic Medicine, Pediatrics, Perinatology and Child Health, Physiology

View Paper: https://www.semanticscholar.org/paper/8b7ab0e6b71da95ceb67e1c43f0526198cbc0f97

Citations in the corpus

• The return of metabolism: biochemistry and physiology of the pentose phosphate pathway (2014, background): “Both in mouse and yeast, G6PDH is transcriptionally induced upon oxidative stress, and by the need for NADPH and PPP intermediates for anabolic reactions such as lipid synthesis and nucleotide synthesis (Kletzien, Harris & Foellmi, 1994; Lee et al., 1999; Stanton, 2012).”
• ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells (2019, background): “In the next step, 6-phosphogluconate dehydrogenase (6PG) catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose-5-phosphate (Ru5P) providing the additional NADPH [249].”
• Mitochondria ROS and mitophagy in acute kidney injury (2022, background): “NADPH is derived from the metabolism of glucose through glycolysis wherein G6PD (glucose-6-phosphate dehydrogenase) is the ratelimiting enzyme [19].”
• Coupling between protein stability and catalytic activity determines pathogenicity of G6PD variants (2017, neutral): “…by protection against oxidative damage (Nóbrega-Pereira et al., 2016), the effects of G6PDdeficiency on human health have likely been underestimated, and it is thus expected that additional consequences of G6PD deficiency will be identified in the future (Spencer and Stanton, 2017; Stanton, 2012).”
• Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases (2023, background): “G6PD catalysis is the rate-limiting step of the pentose phosphate pathway (PPP), which provide nucleotide precursors for DNA replication, as well as reductive power to NADPH for the detoxification of ROS and de novo synthesis of lipid (Stanton, 2012).”