 Alternating access model

The alternating access model describes membrane transport by a carrier protein whose binding region is exposed successively to opposite sides of a cell membrane. A solute can bind on one side, remain associated while the carrier protein changes conformation, and be released on the other. Unlike an open ion channel, this mechanism need not provide a continuous aqueous passage across the cell membrane.^[ref]

The model explains a route, while thermodynamics determines the possible net direction. For an uncharged ideal dilute solute at uniform temperature, with equal standard chemical potentials on the two sides, the molar free energy change for inward transfer isHere $R$ is the molar gas constant. At $298.15\mathrm{K}$, accumulating that solute to ten times its outside concentration costs approximately $5.71\mathrm{kJ}\mathrm{mo}{\mathrm{l}}^{-1}$. Changing which side can reach a binding site does not supply that free energy. Sustained uphill transport requires coupling to another energetically favourable process; at equilibrium, detailed balance excludes a persistent directed pumping cycle.

Structural experiments help test how such access could change. The 2005 NhaA antiporter structure revealed a cytoplasmic funnel and an internal region implicated in ion binding in a pH-downregulated state. The authors proposed movements connecting access and regulation. A structure of one state constrains a transport mechanism, but is not a direct movie of its complete cycle.^[ref] The neutral-solute calculation above illustrates the energetic distinction; the full NhaA cycle also involves coupled charged ions.