Certain key transitions predict dominance of transport phenotype. Free exchange includes all possible transport pathways in one model. To tip the balance of transport toward a single type of proton-coupled transport, rate constants need to favor one pathway over the others. (A) Alternating access rates directly influence coupling if the key transitions for antiport or symport pathways are faster. (B) Substrate off-rates indirectly influence transport by altering the partitioning between futile binding/release on one side of the membrane and productive transport of molecules through key alternating access transitions. Colors are as in Figs. 1, 2, 3, and 5.