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Overflow metabolism

Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate (e.g. glucose) instead of using the respiratory pathway, even in the presence of oxygen.[1] As a result of employing this metabolic strategy, cells excrete (or "overflow") metabolites like lactate, acetate and ethanol. Incomplete oxidation of growth substrates yields less energy (e.g. ATP) than complete oxidation through respiration, and yet overflow metabolism—known as the Warburg effect in the context of cancer[2] and the Crabtree effect in the context of yeast—occurs ubiquitously among fast-growing cells, including bacteria, fungi and mammalian cells.

Based on experimental studies of acetate overflow in Escherichia coli, recent research has offered a general explanation for the association of overflow metabolism with fast growth. According to this theory, the enzymes required for respiration are more costly than those required for partial oxidation of glucose.[3][4] That is, if the cell were to produce enough of these enzymes to support fast growth with respiratory metabolism, it would consume much more energy, carbon and nitrogen (per unit time) than supporting fast growth with an incompletely oxidative metabolism (e.g. fermentation). Given that cells have limited energy resources and fixed physical volume for proteins, there is thought to be a trade-off between efficient energy capture through central metabolism (i.e. respiration) and fast growth achieved through high central-metabolic fluxes (e.g. through fermentation as in yeast).

As an alternative explanation, it was suggested that cells could be limited by the rate with which they can dissipate Gibbs energy to the environment.[5] Using combined thermodynamic and stoichiometric metabolic models in flux balance analyses with (i) growth maximization as objective function and (ii) an identified limit in the cellular Gibbs energy dissipation rate, correct predictions of physiological parameters, intracellular metabolic fluxes and metabolite concentrations were achieved.[5]

See also edit

References edit

  1. ^ Vazquez, Alexei (2017-10-27). Overflow Metabolism: From Yeast to Marathon Runners. Academic Press. ISBN 9780128122082.
  2. ^ Fernandez-de-Cossio-Diaz, Jorge; Vazquez, Alexei (2017-10-18). "Limits of aerobic metabolism in cancer cells". Scientific Reports. 7 (1): 13488. doi:10.1038/s41598-017-14071-y. ISSN 2045-2322. PMC 5647437. PMID 29044214.
  3. ^ Molenaar, Douwe; Berlo, Rogier van; Ridder, Dick de; Teusink, Bas (2009-01-01). "Shifts in growth strategies reflect tradeoffs in cellular economics". Molecular Systems Biology. 5 (1): 323. doi:10.1038/msb.2009.82. ISSN 1744-4292. PMC 2795476. PMID 19888218.
  4. ^ Basan, Markus; Hui, Sheng; Okano, Hiroyuki; Zhang, Zhongge; Shen, Yang; Williamson, James R.; Hwa, Terence (2015-12-03). "Overflow metabolism in Escherichia coli results from efficient proteome allocation". Nature. 528 (7580): 99–104. doi:10.1038/nature15765. ISSN 0028-0836. PMC 4843128. PMID 26632588.
  5. ^ a b Heinemann, Matthias; Leupold, Simeon; Niebel, Bastian (January 2019). "An upper limit on Gibbs energy dissipation governs cellular metabolism" (PDF). Nature Metabolism. 1 (1): 125–132. doi:10.1038/s42255-018-0006-7. ISSN 2522-5812. PMID 32694810. S2CID 104433703.

overflow, metabolism, refers, seemingly, wasteful, strategy, which, cells, incompletely, oxidize, their, growth, substrate, glucose, instead, using, respiratory, pathway, even, presence, oxygen, result, employing, this, metabolic, strategy, cells, excrete, ove. Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate e g glucose instead of using the respiratory pathway even in the presence of oxygen 1 As a result of employing this metabolic strategy cells excrete or overflow metabolites like lactate acetate and ethanol Incomplete oxidation of growth substrates yields less energy e g ATP than complete oxidation through respiration and yet overflow metabolism known as the Warburg effect in the context of cancer 2 and the Crabtree effect in the context of yeast occurs ubiquitously among fast growing cells including bacteria fungi and mammalian cells Based on experimental studies of acetate overflow in Escherichia coli recent research has offered a general explanation for the association of overflow metabolism with fast growth According to this theory the enzymes required for respiration are more costly than those required for partial oxidation of glucose 3 4 That is if the cell were to produce enough of these enzymes to support fast growth with respiratory metabolism it would consume much more energy carbon and nitrogen per unit time than supporting fast growth with an incompletely oxidative metabolism e g fermentation Given that cells have limited energy resources and fixed physical volume for proteins there is thought to be a trade off between efficient energy capture through central metabolism i e respiration and fast growth achieved through high central metabolic fluxes e g through fermentation as in yeast As an alternative explanation it was suggested that cells could be limited by the rate with which they can dissipate Gibbs energy to the environment 5 Using combined thermodynamic and stoichiometric metabolic models in flux balance analyses with i growth maximization as objective function and ii an identified limit in the cellular Gibbs energy dissipation rate correct predictions of physiological parameters intracellular metabolic fluxes and metabolite concentrations were achieved 5 See also editStream metabolism MetabolismReferences edit Vazquez Alexei 2017 10 27 Overflow Metabolism From Yeast to Marathon Runners Academic Press ISBN 9780128122082 Fernandez de Cossio Diaz Jorge Vazquez Alexei 2017 10 18 Limits of aerobic metabolism in cancer cells Scientific Reports 7 1 13488 doi 10 1038 s41598 017 14071 y ISSN 2045 2322 PMC 5647437 PMID 29044214 Molenaar Douwe Berlo Rogier van Ridder Dick de Teusink Bas 2009 01 01 Shifts in growth strategies reflect tradeoffs in cellular economics Molecular Systems Biology 5 1 323 doi 10 1038 msb 2009 82 ISSN 1744 4292 PMC 2795476 PMID 19888218 Basan Markus Hui Sheng Okano Hiroyuki Zhang Zhongge Shen Yang Williamson James R Hwa Terence 2015 12 03 Overflow metabolism in Escherichia coli results from efficient proteome allocation Nature 528 7580 99 104 doi 10 1038 nature15765 ISSN 0028 0836 PMC 4843128 PMID 26632588 a b Heinemann Matthias Leupold Simeon Niebel Bastian January 2019 An upper limit on Gibbs energy dissipation governs cellular metabolism PDF Nature Metabolism 1 1 125 132 doi 10 1038 s42255 018 0006 7 ISSN 2522 5812 PMID 32694810 S2CID 104433703 Retrieved from https en wikipedia org w index php title Overflow metabolism amp oldid 1119242452, wikipedia, wiki, book, books, library,

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