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Sci Rep. 2018 Apr 3;8(1):5576. doi: 10.1038/s41598-018-23528-7.

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

Author information

1
Systems Bioinformatics, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University, Amsterdam, De Boelelaan 1108, 1081HZ, The Netherlands.
2
Division of Molecular Carcinogenesis, The Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Centre for Ecological and Evolutionary Synthesis (CEES), The Department of Biosciences, University of Oslo, Blindernveien 31, 0371, Oslo, Norway.
4
Department of Biotechnology, Delft University of Technology, Delft, The Netherlands.
5
Systems Bioinformatics, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), VU University, Amsterdam, De Boelelaan 1108, 1081HZ, The Netherlands. b.teusink@vu.nl.

Abstract

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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