Coupling efficiency of secondary active transporters

Secondary active transporters are fundamental to a myriad of biological processes. They use the electrochemical gradient of one solute to drive transport of another solute against its concentration gradient. Central to this mechanism is that the transport of one does not occur in the absence of the other. However, like in most of biology, imperfections in the coupling mechanism exist and we argue that these are innocuous and may even be beneficial for the cell. We discuss the energetics and kinetics of alternating-access in secondary transport and focus on the mechanistic aspects of imperfect coupling that give rise to leak pathways. Additionally, inspection of available transporter structures gives valuable insight into coupling mechanics, and we review literature where proteins have been altered to change their coupling efficiency.