Secondary active transport uses the downhill movement of one solute to drive the uphill movement of another. The transporter does not hydrolyze ATP directly; instead, it consumes electrochemical free energy stored in a gradient that was created by another process.

Suppose solute A can move downhill with

$$\Delta G_A<0,$$

while solute B must move uphill with

$$\Delta G_B>0.$$

If one transport cycle obligatorily links the two movements, the combined process can proceed when

$$\boxed{\Delta G_{\rm total}=\Delta G_A+\Delta G_B<0}.$$

This is thermodynamic coupling across a membrane.

Two common arrangements are:

• symport: the coupled solutes move in the same direction;
• antiport: the coupled solutes move in opposite directions.

Example: sodium-glucose symport

Animal cells often maintain a low intracellular $\mathrm{Na^+}$ concentration using the Na$^+$/K$^+$ ATPase. The resulting inward electrochemical gradient for $\mathrm{Na^+}$ can then power a sodium-glucose symporter.

The transporter binds extracellular $\mathrm{Na^+}$ together with glucose. Sodium moves inward down its electrochemical gradient, and the coupled conformational cycle can carry glucose inward even when glucose is already more concentrated inside the cell.

ATP is therefore involved indirectly:

ATP-driven Na+/K+ pump
        ↓
Na+ electrochemical gradient
        ↓
Na+-glucose symporter
        ↓
uphill glucose accumulation

If the sodium gradient collapses, the secondary transporter loses its energy source even if ATP is still present elsewhere in the cell.

Gradient energy can be transferred between species

Secondary transport is not limited to sodium or glucose. Proton gradients drive many bacterial, mitochondrial and plant transport systems. Antiporters can exchange one ion for another and thereby regulate acidity, ion composition and cell volume.

The defining idea is that one transported species moves downhill and pays the thermodynamic cost of moving another species uphill through the same coupled transporter cycle.