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Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation

Vazquez, A and Markert, EK and Oltvai, ZN (2011) Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation. PLoS ONE, 6 (11).

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Abstract

Previous experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from serine biosynthesis, one-carbon metabolism and the glycine cleavage system, and show that the pathway is transcriptionally upregulated in an inducible murine model of Myc-driven liver tumorigenesis. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate - but higher rate of alanine secretion. Thus, in cells using the standard - or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis. © 2011 Vazquez et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Vazquez, A
Markert, EK
Oltvai, ZNoltvai@pitt.eduOLTVAI
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMoreno, YamirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 2 November 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0025881
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
MeSH Headings: Adenosine Triphosphate--biosynthesis; Animals; Carbon--metabolism; Cell Proliferation; Glycine--metabolism; Glycolysis; Kinetics; Liver Neoplasms, Experimental--metabolism; Liver Neoplasms, Experimental--pathology; Mice; Serine--biosynthesis; Transcription, Genetic; Up-Regulation
Other ID: NLM PMC3206798
PubMed Central ID: PMC3206798
PubMed ID: 22073143
Date Deposited: 07 Sep 2012 20:38
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/13993

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