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Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism

The flux of glycolysis is tightly controlled by feed-back and feed-forward allosteric regulations to maintain the body's glucose homeostasis and to respond to cell's growth and energetic needs. Using a mathematical model based on reported mechanisms for the allosteric regulations of the en...

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Autores principales: Mulukutla, Bhanu Chandra, Yongky, Andrew, Daoutidis, Prodromos, Hu, Wei-Shou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049617/
https://www.ncbi.nlm.nih.gov/pubmed/24911170
http://dx.doi.org/10.1371/journal.pone.0098756
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author Mulukutla, Bhanu Chandra
Yongky, Andrew
Daoutidis, Prodromos
Hu, Wei-Shou
author_facet Mulukutla, Bhanu Chandra
Yongky, Andrew
Daoutidis, Prodromos
Hu, Wei-Shou
author_sort Mulukutla, Bhanu Chandra
collection PubMed
description The flux of glycolysis is tightly controlled by feed-back and feed-forward allosteric regulations to maintain the body's glucose homeostasis and to respond to cell's growth and energetic needs. Using a mathematical model based on reported mechanisms for the allosteric regulations of the enzymes, we demonstrate that glycolysis exhibits multiple steady state behavior segregating glucose metabolism into high flux and low flux states. Two regulatory loops centering on phosphofructokinase and on pyruvate kinase each gives rise to the bistable behavior, and together impose more complex flux control. Steady state multiplicity endows glycolysis with a robust switch to transit between the two flux states. Under physiological glucose concentrations the glycolysis flux does not move between the states easily without an external stimulus such as hormonal, signaling or oncogenic cues. Distinct combination of isozymes in glycolysis gives different cell types the versatility in their response to different biosynthetic and energetic needs. Insights from the switch behavior of glycolysis may reveal new means of metabolic intervention in the treatment of cancer and other metabolic disorders through suppression of glycolysis.
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spelling pubmed-40496172014-06-18 Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism Mulukutla, Bhanu Chandra Yongky, Andrew Daoutidis, Prodromos Hu, Wei-Shou PLoS One Research Article The flux of glycolysis is tightly controlled by feed-back and feed-forward allosteric regulations to maintain the body's glucose homeostasis and to respond to cell's growth and energetic needs. Using a mathematical model based on reported mechanisms for the allosteric regulations of the enzymes, we demonstrate that glycolysis exhibits multiple steady state behavior segregating glucose metabolism into high flux and low flux states. Two regulatory loops centering on phosphofructokinase and on pyruvate kinase each gives rise to the bistable behavior, and together impose more complex flux control. Steady state multiplicity endows glycolysis with a robust switch to transit between the two flux states. Under physiological glucose concentrations the glycolysis flux does not move between the states easily without an external stimulus such as hormonal, signaling or oncogenic cues. Distinct combination of isozymes in glycolysis gives different cell types the versatility in their response to different biosynthetic and energetic needs. Insights from the switch behavior of glycolysis may reveal new means of metabolic intervention in the treatment of cancer and other metabolic disorders through suppression of glycolysis. Public Library of Science 2014-06-09 /pmc/articles/PMC4049617/ /pubmed/24911170 http://dx.doi.org/10.1371/journal.pone.0098756 Text en © 2014 Mulukutla et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mulukutla, Bhanu Chandra
Yongky, Andrew
Daoutidis, Prodromos
Hu, Wei-Shou
Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title_full Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title_fullStr Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title_full_unstemmed Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title_short Bistability in Glycolysis Pathway as a Physiological Switch in Energy Metabolism
title_sort bistability in glycolysis pathway as a physiological switch in energy metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049617/
https://www.ncbi.nlm.nih.gov/pubmed/24911170
http://dx.doi.org/10.1371/journal.pone.0098756
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