Document Detail


Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells.
MedLine Citation:
PMID:  20935507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glutaminolysis and Warburg effect are the two most noticeable metabolic features of tumor cells whereas their biological significance in cell proliferation remains elusive. A widely accepted current hypothesis is that tumor cells use glutamine as a preferred carbon source for energy and reducing power, which has been used to explain both glutaminolysis and the Warburg effect. Here we provide evidence to show that supplying nitrogen, not the carbon skeleton, underlies the major biological importance of glutaminolysis for proliferating cells. We show alternative nitrogen supplying mechanisms rescue cell proliferation in glutamine-free media. Particularly, we show that ammonia is sufficient to maintain a long-term survival and proliferation of Hep3B in glutamine-free media. We also observed that nitrogen source restriction repressed carbon metabolic pathways including glucose utilization. Based on these new observations and metabolic pathways well established in published literature, we propose an alternative model that cellular demand for glutamate as a key molecule in nitrogen anabolism is the driving force of glutaminolysis in proliferating cells. Our model suggests that the Warburg effect may be a metabolic consequence secondary to the nitrogen anabolism.
Authors:
Meng Meng; Shuyang Chen; Taotao Lao; Dongming Liang; Nianli Sang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-25
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  9     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-27     Completed Date:  2011-03-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3921-32     Citation Subset:  IM    
Affiliation:
Department of Biology, College of Arts & Sciences, Drexel University, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Alanine / metabolism
Ammonia / metabolism
Aspartic Acid / metabolism
Carbon / metabolism
Cell Line, Tumor
Cell Proliferation*
Energy Metabolism
Glucose / metabolism
Glutamine / metabolism*
Humans
Ketoglutaric Acids / metabolism
Metabolism*
Mitochondria / metabolism
Neoplasms / metabolism
Nitrogen / metabolism*
Nucleic Acids / biosynthesis
Stress, Physiological
Grant Support
ID/Acronym/Agency:
K01-CA098809/CA/NCI NIH HHS; R01 CA129494-05/CA/NCI NIH HHS; R01-CA129494/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Ketoglutaric Acids; 0/Nucleic Acids; 328-50-7/alpha-ketoglutaric acid; 50-99-7/Glucose; 56-41-7/Alanine; 56-84-8/Aspartic Acid; 56-85-9/Glutamine; 7440-44-0/Carbon; 7664-41-7/Ammonia; 7727-37-9/Nitrogen
Comments/Corrections

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


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