5.3 Active transport and pumps

Active Transport and Cellular Homeostasis

Active transport moves molecules against their concentration gradient, which requires energy. Without it, cells couldn't maintain the specific internal conditions they need to function. This process is responsible for everything from keeping neurons ready to fire to absorbing glucose from your intestines.

There are two main types: primary active transport, which burns ATP directly, and secondary active transport, which piggybacks on gradients that primary transport already built. Both are covered below.

Active vs. Passive Transport

Passive transport moves molecules down their concentration gradient (from high to low concentration). It doesn't require energy because molecules naturally move this way on their own. Diffusion and facilitated diffusion are both passive.

Active transport moves molecules against their concentration gradient (from low to high concentration). This can't happen spontaneously, so the cell has to spend energy, typically from ATP hydrolysis. Active transport is what allows cells to accumulate specific molecules or ions on one side of the membrane, maintaining concentration differences that the cell depends on.

Structure of ATP-Powered Pumps

ATP-powered pumps are integral membrane proteins that span the lipid bilayer. They bind ATP, hydrolyze it, and use the released energy to physically change shape, pushing specific ions or molecules across the membrane.

The most well-studied example is the sodium-potassium pump ($Na^+/K^+$ ATPase). It has two subunits:

• α subunit: Contains the ATP binding site and the ion binding sites. This is where the actual transport work happens.
• β subunit: Helps the pump fold correctly and ensures it gets delivered to the correct location in the membrane.

How the $Na^+/K^+$ pump works, step by step:

1. Three $Na^+$ ions from inside the cell bind to the pump's α subunit.
2. ATP binds and is hydrolyzed, transferring a phosphate group to the pump.
3. This phosphorylation causes the pump to change shape, opening toward the outside of the cell and releasing the three $Na^+$ ions.
4. Two $K^+$ ions from outside the cell bind to the pump.
5. The phosphate group is released, causing the pump to return to its original shape.
6. The pump opens toward the inside of the cell and releases the two $K^+$ ions.

Net result per ATP: 3 $Na^+$ out, 2 $K^+$ in. Because the pump moves unequal charges (3 positive ions out vs. 2 positive ions in), it's electrogenic, meaning it contributes directly to the electrical potential across the membrane.

Primary and Secondary Active Transport

Primary active transport directly uses ATP hydrolysis as its energy source. Examples include:

• The $Na^+/K^+$ ATPase (described above)
• The calcium pump ($Ca^{2+}$ ATPase), which pumps $Ca^{2+}$ out of the cytoplasm into the ER or out of the cell, keeping cytoplasmic calcium levels very low

Secondary active transport does not use ATP directly. Instead, it harnesses the electrochemical gradient that primary active transport created. For instance, the $Na^+/K^+$ pump builds a steep $Na^+$ gradient. Secondary transporters then let $Na^+$ flow back down that gradient, and they use that energy to drag another molecule against its gradient.

There are two types of coupled transport in secondary active transport:

• Symport (cotransport): Both molecules move in the same direction. Example: the $Na^+$-glucose symporter in intestinal cells uses the inward flow of $Na^+$ to pull glucose into the cell against glucose's own gradient.
• Antiport (exchange): The two molecules move in opposite directions. Example: the $Na^+/H^+$ antiporter uses inward $Na^+$ flow to push $H^+$ out of the cell, helping regulate intracellular pH.

Energy Requirements and Significance of Active Transport

Energy Requirements

Active transport demands a continuous supply of ATP. Cells dedicate a large fraction of their total energy budget to keeping pumps running. Neurons, for example, use roughly 60–70% of their ATP just to power the $Na^+/K^+$ ATPase, because maintaining the ion gradient is essential for transmitting signals.

If ATP production drops (during oxygen deprivation, for instance), pumps slow or stop, gradients collapse, and cells rapidly lose function.

Why Active Transport Matters

1. Resting membrane potential: The $Na^+/K^+$ pump and the ion gradients it maintains are the foundation of the membrane potential that nerve and muscle cells need to fire.
2. Nutrient uptake: Secondary active transport drives absorption of glucose and amino acids, especially in intestinal and kidney cells.
3. pH and ion regulation: Antiporters help control intracellular pH and ion concentrations, which enzymes and signaling pathways depend on.
4. Cell volume control: By regulating ion balance across the membrane, active transport prevents cells from swelling or shrinking due to osmotic water movement.

When active transport fails, the consequences can be severe. Impaired ion homeostasis is linked to neurological conditions like epilepsy, and defects in nutrient transporters can cause metabolic disorders and impaired cell growth.