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  Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells

Gruning, N. M., Rinnerthaler, M., Bluemlein, K., Mulleder, M., Wamelink, M. M., Lehrach, H., et al. (2011). Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells. Cell Metabolism, 14(3), 415-27. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21907146 http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=273298&_user=28761&_pii=S1550413111003007&_check=y&_origin=article&_zone=toolbar&_coverDate=07-Sep-2011&view=c&originContentFamily=serial&wchp=dGLzVlS-zSkzS&md5=48391fcc540f5a9b4db859d804a04c12/1-s2.0-S1550413111003007-main.pdf http://pdn.sciencedirect.com/science?_ob=MiamiImageURL&_cid=273298&_user=28761&_pii=S1550413111003007&_check=y&_origin=article&_zone=toolbar&_coverDate=07-Sep-2011&view=c&originContentFamily=serial&wchp=dGLzVlB-zSkWA&md5=48391fcc540f5a9b4db859d804a04c12/1-s2.0-S1550413111003007-main.pdf.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-78DE-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-78DF-B
Genre: Journal Article

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 Creators:
Gruning, N. M., Author
Rinnerthaler, M., Author
Bluemlein, K.1, Author              
Mulleder, M., Author
Wamelink, M. M., Author
Lehrach, H.1, Author              
Jakobs, C., Author
Breitenbach, M., Author
Ralser, M.1, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: Cell Proliferation; Cell Respiration/*physiology; Chromatography, Liquid; *Feedback, Physiological; Galactose/metabolism; Gene Expression Regulation, Fungal; Glucose/metabolism; Glycolysis/*physiology; Oxidation-Reduction; Oxidative Stress/genetics; Pentose Phosphate Pathway; Phosphoenolpyruvate/*metabolism; Polymerase Chain Reaction; Pyruvate Kinase/genetics/*metabolism; Reactive Oxygen Species/metabolism; Saccharomyces cerevisiae/genetics/*metabolism; Saccharomyces cerevisiae Proteins/genetics/metabolism; Tandem Mass Spectrometry; Triose-Phosphate Isomerase/genetics/*metabolism
 Abstract: In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism when respiration is activated. Low PYK activity activated yeast respiration. However, levels of reactive oxygen species (ROS) did not increase, and cells gained resistance to oxidants. This adaptation was attributable to accumulation of the PYK substrate phosphoenolpyruvate (PEP). PEP acted as feedback inhibitor of the glycolytic enzyme triosephosphate isomerase (TPI). TPI inhibition stimulated the pentose phosphate pathway, increased antioxidative metabolism, and prevented ROS accumulation. Thus, a metabolic feedback loop, initiated by PYK, mediated by its substrate and acting on TPI, stimulates redox metabolism in respiring cells. Originating from a single catalytic step, this autonomous reconfiguration of central carbon metabolism prevents oxidative stress upon shifts between fermentation and respiration.

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Title: Cell Metabolism
Source Genre: Journal
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Pages: - Volume / Issue: 14 (3) Sequence Number: - Start / End Page: 415 - 27 Identifier: ISSN: 1932-7420 (Electronic) 1550-4131 (Linking)