Coupling mechanisms in active transport.

In primary and secondary active transport, the mobility and specificity of the carrier are controlled, over the course of the transport reaction, in accordance with a set of 'rules'. The rules are shown to depend on two mechanisms: a substrate--either the driving substrate (a transported ion or ATP) or the driven substrate--may shift a conformational equilibrium or accelerate a rate-limiting conformational change. From an analysis of coupling mechanisms the following conclusions emerge. (i) The ratio of coupled to uncoupled flux, which should be large, cannot be greater than the ratio of substrate dissociation constants in an initial complex and a conformationally altered state. A minimum value for the increased binding force can be estimated from steady-state constants. (ii) In an ordered mechanism, slippage is expected at high concentrations of the substrate adding to the carrier second, while slippage of the first substrate should remain low. (iii) Slippage in coupled transport is minimized if the driven substrate is last on in loading the carrier and last off in unloading, while the reverse order makes the affinity high in loading and low in unloading, as required for efficient transfer from one compartment to another; hence the preferred mechanism may depend on prevailing physiological conditions. (iv) A coupled transport system can be transformed into a facilitated system for one substrate or both if the control of carrier mobility is undermined through modification of the carrier.