Low affinity membrane transporters increase the net substrate uptake rate by reducing substrate efflux In collaboration with :

Cells require membrane-located transporter proteins to import energy and carbon sources from the environment. Many organisms have several similar transporters for the same nutrient, which differ in their affinity. Typically, high affinity transporters are expressed when substrate is scarce and low affinity ones when substrate is more abundant. The benefit of using low affinity transporters when high affinity ones are available remains unclear. We investigate two hypotheses: (1) It was previously hypothesised that that a trade-off between the affinity and the maximal catalytic rate explains this phenomenon. We find some theoretical and experimental support for this hypothesis, but no conclusive evidence. (2) We propose a new hypothesis: namely that for uptake by facilitated diffusion, at saturating extracellular substrate concentrations, a lowering of the affinity can in itself enhance the net substrate uptake rate. Reducing the transporter affinity reduces the substrate efflux rate, and, as a consequence, an optimal transporter exists affinity that is dependent on the external substrate concentration. This tuning of affinity to external concentrations might explain the abundance of glucose transporters in yeast. Indeed, an in silico analysis of glycolysis in Saccharomyces cerevisiae shows that using the low affinity HXT3 transporter in stead of the high affinity HXT6 enhances the steady state flux by 36%. Our results provide a novel reason for the presence of low affinity transport systems that might have implications for more general enzyme catalysed conversions.