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:	Bhanu Chandra Mulukutla, Andrew Yongky, Prodromos Daoutidis, Wei-Shou Hu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d141004305a44cbea637ebfcfd05a97c
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spelling	oai:doaj.org-article:d141004305a44cbea637ebfcfd05a97c2021-11-18T08:16:36ZBistability in glycolysis pathway as a physiological switch in energy metabolism.1932-620310.1371/journal.pone.0098756https://doaj.org/article/d141004305a44cbea637ebfcfd05a97c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24911170/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Bhanu Chandra MulukutlaAndrew YongkyProdromos DaoutidisWei-Shou HuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e98756 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bhanu Chandra Mulukutla Andrew Yongky Prodromos Daoutidis Wei-Shou Hu Bistability in glycolysis pathway as a physiological switch in energy metabolism.
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.
format	article
author	Bhanu Chandra Mulukutla Andrew Yongky Prodromos Daoutidis Wei-Shou Hu
author_facet	Bhanu Chandra Mulukutla Andrew Yongky Prodromos Daoutidis Wei-Shou Hu
author_sort	Bhanu Chandra Mulukutla
title	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_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_sort	bistability in glycolysis pathway as a physiological switch in energy metabolism.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d141004305a44cbea637ebfcfd05a97c
work_keys_str_mv	AT bhanuchandramulukutla bistabilityinglycolysispathwayasaphysiologicalswitchinenergymetabolism AT andrewyongky bistabilityinglycolysispathwayasaphysiologicalswitchinenergymetabolism AT prodromosdaoutidis bistabilityinglycolysispathwayasaphysiologicalswitchinenergymetabolism AT weishouhu bistabilityinglycolysispathwayasaphysiologicalswitchinenergymetabolism
_version_	1718422014142709760

Bistability in glycolysis pathway as a physiological switch in energy metabolism.

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