Glucose-6-phosphate dehydrogenase, NADPH, and cell survival
TLDR
It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes.Abstract:
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.read more
Citations
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Journal ArticleDOI
The return of metabolism: biochemistry and physiology of the pentose phosphate pathway
Anna Stincone,Alessandro Prigione,Thorsten Cramer,Mirjam M.C. Wamelink,Kate Campbell,Eric Cheung,Viridiana Olin-Sandoval,Nana-Maria Grüning,Antje Krüger,Mohammad Tauqeer Alam,Markus A. Keller,Michael Breitenbach,Kevin M. Brindle,Joshua D. Rabinowitz,Markus Ralser,Markus Ralser +15 more
TL;DR: The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism as discussed by the authors, which shares reactions with the Entner-Doudoroff pathway and the Calvin cycle and divides into an oxidative and non-oxidative branch.
Journal ArticleDOI
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Anastasiya V. Snezhkina,Anna V. Kudryavtseva,Olga L. Kardymon,Maria V Savvateeva,Nataliya V. Melnikova,George S. Krasnov,Alexey A. Dmitriev +6 more
TL;DR: This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.
Journal ArticleDOI
Regulation of the pentose phosphate pathway in cancer
Peng Jiang,Wenjing Du,Mian Wu +2 more
TL;DR: A better understanding of how the PPP is reprogrammed and the mechanism underlying the balance between glycolysis and PPP flux in cancer will be valuable in developing therapeutic strategies targeting this pathway.
Journal ArticleDOI
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Jiangbin Ye,Jing Fan,Sriram Venneti,Ying Wooi Wan,Bruce R. Pawel,Ji Zhang,Lydia W.S. Finley,Chao Lu,Tullia Lindsten,Justin R. Cross,Guoliang Qing,Zhandong Liu,M. Celeste Simon,Joshua D. Rabinowitz,Craig B. Thompson +14 more
TL;DR: It is demonstrated that the serine catabolic enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth.
References
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Journal ArticleDOI
TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Karim Bensaad,Atsushi Tsuruta,Mary A. Selak,M. Nieves Calvo Vidal,Katsunori Nakano,Ramon Bartrons,Eyal Gottlieb,Karen H. Vousden +7 more
TL;DR: expression of TIGAR may modulate the apoptotic response to p53, allowing survival in the face of mild or transient stress signals that may be reversed or repaired, and the decrease of intracellular ROS levels in response to TIGar may also play a role in the ability of p53 to protect from the accumulation of genomic damage.
Journal ArticleDOI
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
Katrin Düvel,Jessica L. Yecies,Suchithra Menon,Pichai Raman,Alex Lipovsky,Amanda Souza,Ellen Triantafellow,Qicheng Ma,Regina Gorski,Stephen Cleaver,Matthew G. Vander Heiden,Jeffrey P. MacKeigan,Peter Finan,Clary B. Clish,Leon Murphy,Brendan D. Manning +15 more
TL;DR: It is demonstrated that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis, through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor and sterol regulatory element-binding protein.
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
Katrin Düvel,Jessica L. Yecies,Suchithra Menon,Pichai Raman,Ellen Triantafellow,Qicheng Ma,Regina Gorski,Stephen Cleaver,Jeffrey P. MacKeigan,Peter Finan,Leon Murphy,Brendan D. Manning,Alex Lipovsky,Amanda Souza,Matthew G. Vander Heiden,Clary B. Clish +15 more
Abstract: Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1alpha) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease.
Book ChapterDOI
Glucose-6-phosphate Dehydrogenase
TL;DR: G6P-DH is inhibited by primaquine and other 8-aminoquinolines (antimalarial drugs) in millimolar concentration, as well as by phenylhydrazine, Nevertheless, the therapeutic concentration of these substances is more than tenfold lower and therefore, they have no significant effect on the measurements.
Journal ArticleDOI
Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling.
Henry Jay Forman,Martine Torres +1 more
TL;DR: One of the subunits of the phagocyte NAD PH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes, present at the plasma membrane from resident plasma membrane and cytosolic protein components.