= 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>.<Molecular Biology of the Cell, 4th edition by Bruce Alberts and others>[Chapter 11, Carrier Proteins and Active Membrane Transport: alternating exposure of binding sites]{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 is
$$
\Delta G_{\mathrm{in}}=RT\ln\!\left(\frac{c_{\mathrm{in}}}{c_{\mathrm{out}}}\right).
$$
Here $R$ is the <molar gas constant>. At $298.15\,\mathrm K$, accumulating that <solute> to ten times its outside <concentration> costs approximately $5.71\,\mathrm{kJ\,mol^{-1}}$. 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.<Structure of a Na+ H+ antiporter and insights into mechanism of action and regulation by pH by Carola Hunte and others>[Abstract; Figures 2–3, architecture and substrate passage; Figure 5, proposed mechanism]{ref} The neutral-solute calculation above illustrates the energetic distinction; the full <NhaA> cycle also involves coupled charged <ions>.
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