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Differential incorporation of glucose into biomass during Warburg metabolism.

Chen YJ, Huang X, Mahieu NG, Cho K, Schaefer J, Patti GJ - Biochemistry (2014)

Bottom Line: The majority of this glucose carbon is secreted from the cell as lactate.The fate of the remaining glucose carbon, however, has not been well-characterized.We provide a list of specific intracellular metabolites that become enriched after being labeled for 48 h and quantitate the fraction of consumed glucose that ends up in proteins, peptides, sugars/glycerol, and lipids.

View Article: PubMed Central - PubMed

Affiliation: Departments of †Chemistry, ‡Genetics, and §Medicine, Washington University in St. Louis , St. Louis, Missouri 63130, United States.

ABSTRACT
It is well established that most cancer cells take up an increased amount of glucose relative to that taken up by normal differentiated cells. The majority of this glucose carbon is secreted from the cell as lactate. The fate of the remaining glucose carbon, however, has not been well-characterized. Here we apply a novel combination of metabolomic technologies to track uniformly labeled glucose in HeLa cancer cells. We provide a list of specific intracellular metabolites that become enriched after being labeled for 48 h and quantitate the fraction of consumed glucose that ends up in proteins, peptides, sugars/glycerol, and lipids.

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Related in: MedlinePlus

Isotopologue patterns of adenine, glycine, andATP as determinedby LC/MS. Data are from HeLa cells cultured in 50% [U-13C]glucose and 50% natural-abundance glucose for 48 h.
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fig1: Isotopologue patterns of adenine, glycine, andATP as determinedby LC/MS. Data are from HeLa cells cultured in 50% [U-13C]glucose and 50% natural-abundance glucose for 48 h.

Mentions: Interestingly, however, purines were only minimallylabeled, presumablybecause HeLa cells use glycine in the medium as a precursor insteadof glucose.7 Adenine is presented as arepresentative example in Figure 1. The labelingpattern shows that <10% of adenine incorporates 13C.The percentage of adenine incorporating multiple 13C atomsis near the detection limit. These data are consistent with the labelingpatterns of adenosine and adenosine triphosphate (ATP). Adenosineand ATP are composed of an adenine ring of five carbons and a ribosesugar of five carbons. Our results indicate that the ribose sugarof adenosine and ATP is enriched from glucose. The labeling of thefive remaining carbons that form the adenine ring is minimal, witha pattern that is consistent with that detected for free adenine.Further, we do not observe 13C labeling of glycine. Itwas previously suggested that consumed glycine supports denovo purine synthesis in rapidly dividing cancer cells.7,8 Our results are consistent with this finding. Despite taking upincreased levels of glucose, rapidly dividing HeLa cells use verylittle glucose carbon for de novo purine synthesis.


Differential incorporation of glucose into biomass during Warburg metabolism.

Chen YJ, Huang X, Mahieu NG, Cho K, Schaefer J, Patti GJ - Biochemistry (2014)

Isotopologue patterns of adenine, glycine, andATP as determinedby LC/MS. Data are from HeLa cells cultured in 50% [U-13C]glucose and 50% natural-abundance glucose for 48 h.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4116146&req=5

fig1: Isotopologue patterns of adenine, glycine, andATP as determinedby LC/MS. Data are from HeLa cells cultured in 50% [U-13C]glucose and 50% natural-abundance glucose for 48 h.
Mentions: Interestingly, however, purines were only minimallylabeled, presumablybecause HeLa cells use glycine in the medium as a precursor insteadof glucose.7 Adenine is presented as arepresentative example in Figure 1. The labelingpattern shows that <10% of adenine incorporates 13C.The percentage of adenine incorporating multiple 13C atomsis near the detection limit. These data are consistent with the labelingpatterns of adenosine and adenosine triphosphate (ATP). Adenosineand ATP are composed of an adenine ring of five carbons and a ribosesugar of five carbons. Our results indicate that the ribose sugarof adenosine and ATP is enriched from glucose. The labeling of thefive remaining carbons that form the adenine ring is minimal, witha pattern that is consistent with that detected for free adenine.Further, we do not observe 13C labeling of glycine. Itwas previously suggested that consumed glycine supports denovo purine synthesis in rapidly dividing cancer cells.7,8 Our results are consistent with this finding. Despite taking upincreased levels of glucose, rapidly dividing HeLa cells use verylittle glucose carbon for de novo purine synthesis.

Bottom Line: The majority of this glucose carbon is secreted from the cell as lactate.The fate of the remaining glucose carbon, however, has not been well-characterized.We provide a list of specific intracellular metabolites that become enriched after being labeled for 48 h and quantitate the fraction of consumed glucose that ends up in proteins, peptides, sugars/glycerol, and lipids.

View Article: PubMed Central - PubMed

Affiliation: Departments of †Chemistry, ‡Genetics, and §Medicine, Washington University in St. Louis , St. Louis, Missouri 63130, United States.

ABSTRACT
It is well established that most cancer cells take up an increased amount of glucose relative to that taken up by normal differentiated cells. The majority of this glucose carbon is secreted from the cell as lactate. The fate of the remaining glucose carbon, however, has not been well-characterized. Here we apply a novel combination of metabolomic technologies to track uniformly labeled glucose in HeLa cancer cells. We provide a list of specific intracellular metabolites that become enriched after being labeled for 48 h and quantitate the fraction of consumed glucose that ends up in proteins, peptides, sugars/glycerol, and lipids.

Show MeSH
Related in: MedlinePlus