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Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux

Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear, e...

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Autores principales: Bosdriesz, Evert, Wortel, Meike T., Haanstra, Jurgen R., Wagner, Marijke J., de la Torre Cortés, Pilar, Teusink, Bas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883050/
https://www.ncbi.nlm.nih.gov/pubmed/29615663
http://dx.doi.org/10.1038/s41598-018-23528-7
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author Bosdriesz, Evert
Wortel, Meike T.
Haanstra, Jurgen R.
Wagner, Marijke J.
de la Torre Cortés, Pilar
Teusink, Bas
author_facet Bosdriesz, Evert
Wortel, Meike T.
Haanstra, Jurgen R.
Wagner, Marijke J.
de la Torre Cortés, Pilar
Teusink, Bas
author_sort Bosdriesz, Evert
collection PubMed
description Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear, especially when additional nutrient sensors are present. Here, we investigate two hypotheses. It was previously hypothesized that there is a trade-off between the affinity and the catalytic efficiency of transporters, and we find some but no definitive support for it. Additionally, we propose that for uptake by facilitated diffusion, at saturating substrate concentrations, lowering the affinity enhances the net uptake rate by reducing substrate efflux. As a consequence, there exists an optimal, external-substrate-concentration dependent transporter affinity. A computational model of Saccharomyces cerevisiae glycolysis shows that using the low affinity HXT3 transporter instead of the high affinity HXT6 enhances the steady-state flux by 36%. We tried to test this hypothesis with yeast strains expressing a single glucose transporter modified to have either a high or a low affinity. However, due to the intimate link between glucose perception and metabolism, direct experimental proof for this hypothesis remained inconclusive. Still, our theoretical results provide a novel reason for the presence of low-affinity transport systems.
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spelling pubmed-58830502018-04-09 Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux Bosdriesz, Evert Wortel, Meike T. Haanstra, Jurgen R. Wagner, Marijke J. de la Torre Cortés, Pilar Teusink, Bas Sci Rep Article Many organisms have several similar transporters with different affinities for the same substrate. Typically, high-affinity transporters are expressed when substrate is scarce and low-affinity ones when it is abundant. The benefit of using low instead of high-affinity transporters remains unclear, especially when additional nutrient sensors are present. Here, we investigate two hypotheses. It was previously hypothesized that there is a trade-off between the affinity and the catalytic efficiency of transporters, and we find some but no definitive support for it. Additionally, we propose that for uptake by facilitated diffusion, at saturating substrate concentrations, lowering the affinity enhances the net uptake rate by reducing substrate efflux. As a consequence, there exists an optimal, external-substrate-concentration dependent transporter affinity. A computational model of Saccharomyces cerevisiae glycolysis shows that using the low affinity HXT3 transporter instead of the high affinity HXT6 enhances the steady-state flux by 36%. We tried to test this hypothesis with yeast strains expressing a single glucose transporter modified to have either a high or a low affinity. However, due to the intimate link between glucose perception and metabolism, direct experimental proof for this hypothesis remained inconclusive. Still, our theoretical results provide a novel reason for the presence of low-affinity transport systems. Nature Publishing Group UK 2018-04-03 /pmc/articles/PMC5883050/ /pubmed/29615663 http://dx.doi.org/10.1038/s41598-018-23528-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Bosdriesz, Evert
Wortel, Meike T.
Haanstra, Jurgen R.
Wagner, Marijke J.
de la Torre Cortés, Pilar
Teusink, Bas
Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title_full Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title_fullStr Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title_full_unstemmed Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title_short Low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
title_sort low affinity uniporter carrier proteins can increase net substrate uptake rate by reducing efflux
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883050/
https://www.ncbi.nlm.nih.gov/pubmed/29615663
http://dx.doi.org/10.1038/s41598-018-23528-7
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