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Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells

Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. We have predicted that a fraction of the synthesized serine is routed to a pathway for ATP production. The pathway is composed by reactions from serine synthesis, one-carbon...

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Autores principales: Tedeschi, P M, Markert, E K, Gounder, M, Lin, H, Dvorzhinski, D, Dolfi, S C, Chan, L L-Y, Qiu, J, DiPaola, R S, Hirshfield, K M, Boros, L G, Bertino, J R, Oltvai, Z N, Vazquez, A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920946/
https://www.ncbi.nlm.nih.gov/pubmed/24157871
http://dx.doi.org/10.1038/cddis.2013.393
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author Tedeschi, P M
Markert, E K
Gounder, M
Lin, H
Dvorzhinski, D
Dolfi, S C
Chan, L L-Y
Qiu, J
DiPaola, R S
Hirshfield, K M
Boros, L G
Bertino, J R
Oltvai, Z N
Vazquez, A
author_facet Tedeschi, P M
Markert, E K
Gounder, M
Lin, H
Dvorzhinski, D
Dolfi, S C
Chan, L L-Y
Qiu, J
DiPaola, R S
Hirshfield, K M
Boros, L G
Bertino, J R
Oltvai, Z N
Vazquez, A
author_sort Tedeschi, P M
collection PubMed
description Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. We have predicted that a fraction of the synthesized serine is routed to a pathway for ATP production. The pathway is composed by reactions from serine synthesis, one-carbon (folate) metabolism and the glycine cleavage system (SOG pathway). Here we show that the SOG pathway is upregulated at the level of gene expression in a subset of human tumors and that its level of expression correlates with gene signatures of cell proliferation and Myc target activation. We have also estimated the SOG pathway metabolic flux in the NCI60 tumor-derived cell lines, using previously reported exchange fluxes and a personalized model of cell metabolism. We find that the estimated rates of reactions in the SOG pathway are highly correlated with the proliferation rates of these cell lines. We also observe that the SOG pathway contributes significantly to the energy requirements of biosynthesis, to the NADPH requirement for fatty acid synthesis and to the synthesis of purines. Finally, when the PC-3 prostate cancer cell line is treated with the antifolate methotrexate, we observe a decrease in the ATP levels, AMP kinase activation and a decrease in ribonucleotides and fatty acids synthesized from [1,2-(13)C(2)]-D-glucose as the single tracer. Taken together our results indicate that the SOG pathway activity increases with the rate of cell proliferation and it contributes to the biosynthetic requirements of purines, ATP and NADPH of cancer cells.
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spelling pubmed-39209462014-02-13 Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells Tedeschi, P M Markert, E K Gounder, M Lin, H Dvorzhinski, D Dolfi, S C Chan, L L-Y Qiu, J DiPaola, R S Hirshfield, K M Boros, L G Bertino, J R Oltvai, Z N Vazquez, A Cell Death Dis Original Article Recent observations on cancer cell metabolism indicate increased serine synthesis from glucose as a marker of poor prognosis. We have predicted that a fraction of the synthesized serine is routed to a pathway for ATP production. The pathway is composed by reactions from serine synthesis, one-carbon (folate) metabolism and the glycine cleavage system (SOG pathway). Here we show that the SOG pathway is upregulated at the level of gene expression in a subset of human tumors and that its level of expression correlates with gene signatures of cell proliferation and Myc target activation. We have also estimated the SOG pathway metabolic flux in the NCI60 tumor-derived cell lines, using previously reported exchange fluxes and a personalized model of cell metabolism. We find that the estimated rates of reactions in the SOG pathway are highly correlated with the proliferation rates of these cell lines. We also observe that the SOG pathway contributes significantly to the energy requirements of biosynthesis, to the NADPH requirement for fatty acid synthesis and to the synthesis of purines. Finally, when the PC-3 prostate cancer cell line is treated with the antifolate methotrexate, we observe a decrease in the ATP levels, AMP kinase activation and a decrease in ribonucleotides and fatty acids synthesized from [1,2-(13)C(2)]-D-glucose as the single tracer. Taken together our results indicate that the SOG pathway activity increases with the rate of cell proliferation and it contributes to the biosynthetic requirements of purines, ATP and NADPH of cancer cells. Nature Publishing Group 2013-10 2013-10-24 /pmc/articles/PMC3920946/ /pubmed/24157871 http://dx.doi.org/10.1038/cddis.2013.393 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
Tedeschi, P M
Markert, E K
Gounder, M
Lin, H
Dvorzhinski, D
Dolfi, S C
Chan, L L-Y
Qiu, J
DiPaola, R S
Hirshfield, K M
Boros, L G
Bertino, J R
Oltvai, Z N
Vazquez, A
Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title_full Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title_fullStr Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title_full_unstemmed Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title_short Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells
title_sort contribution of serine, folate and glycine metabolism to the atp, nadph and purine requirements of cancer cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920946/
https://www.ncbi.nlm.nih.gov/pubmed/24157871
http://dx.doi.org/10.1038/cddis.2013.393
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