Document Detail

The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism.
MedLine Citation:
PMID:  21106670     Owner:  NLM     Status:  MEDLINE    
Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose deprivation led to a marked reduction in glutamine uptake and progressive cellular atrophy in multiple mammalian cell types. Despite the continuous presence of growth factor and an abundant supply of extracellular glutamine, interleukin-3 (IL-3)-dependent cells were unable to maintain TCA cycle metabolite pools or receptor-dependent signal transduction when deprived of glucose. This was due at least in part to down-regulation of IL-3 receptor α (IL-3Rα) surface expression in the absence of glucose. Treatment of glucose-starved cells with N-acetylglucosamine (GlcNAc) to maintain hexosamine biosynthesis restored mitochondrial metabolism and cell growth by promoting IL-3-dependent glutamine uptake and metabolism. Thus, glucose metabolism through the hexosamine biosynthetic pathway is required to sustain sufficient growth factor signaling and glutamine uptake to support cell growth and survival.
Kathryn E Wellen; Chao Lu; Anthony Mancuso; Johanna M S Lemons; Michael Ryczko; James W Dennis; Joshua D Rabinowitz; Hilary A Coller; Craig B Thompson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  Genes & development     Volume:  24     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-02-18     Revised Date:  2014-07-10    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2784-99     Citation Subset:  IM    
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MeSH Terms
Acetylglucosamine / pharmacology
Biological Transport
Cell Survival
Citric Acid Cycle
Glucose / metabolism*
Glutamine / metabolism*
Hexosamines / biosynthesis*
Intercellular Signaling Peptides and Proteins / pharmacology
Metabolic Networks and Pathways*
Signal Transduction
Grant Support
P01 CA104838/CA/NCI NIH HHS; R01 CA105463/CA/NCI NIH HHS
Reg. No./Substance:
0/Hexosamines; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-3; 0RH81L854J/Glutamine; IY9XDZ35W2/Glucose; V956696549/Acetylglucosamine
Comment In:
Nat Rev Cancer. 2011 Feb;11(2):80   [PMID:  21322292 ]
Genes Dev. 2010 Dec 15;24(24):2717-22   [PMID:  21159812 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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