Since GLUT1 is highly expressed in red blood cells, they have been used as the most convenient system in which to study the kinetics of its transport. There are two prominent features revealed by these studies that must be accommodated in any model. On the one hand the normal net transport of glucose occurs without input of energy from any source other than the concentration gradient, on the other hand downhill movement of one type of sugar can be coupled to uphill movement of another (see Fig. 13), a phenomenon called counter-flow or counter-transport [322–325]. A closely related phenomenon is trans-stimulation, an increase in influx when internal concentration is increased or an increase in efflux when external concentration is increased (see Fig. 13 and, for a quantitative example, Appendix D). In terms of a simple carrier model, the observation of net glucose transport when it is the only substrate implies that both the loaded and unloaded forms of the carrier can change conformation thus altering exposure of the binding site. This allows transport of solute in one direction to occur without transport in the opposite direction, i.e. the transport is not an obligatory exchange. Similarly counter-transport or trans-stimulation imply that the rate constants for the conformation changes when the carrier is loaded are at least comparable to those for the unloaded carrier so that solute on the trans side can assist transport from the cis side by increasing the rate of return of the carrier.
Fig. 13 Interpretation of net flux of a single solute, obligatory exchange, and trans-stimulation in terms of a simple carrier model. In each case the concentration of the first solute (filled black circle) is higher on the cis side (left) than on the trans side (right). a Net flux of solute from cis to trans is supported by return of the free carrier. b If return of the carrier is only possible with a solute bound, there is obligatory exchange, either self-exchange or counter-transport of another solute (circle). c Trans-stimulation is a combination of these two effects. Flux of the first solute from cis to trans can be increased if there is more solute (either sort) on the trans side (here the right) provided that increases the rate of return of the carrier—i.e. it increases the rate of conformation changes of the carrier from trans-facing to cis-facing