Cell membranes regulate the passage of substances into and out of the cell. Membrane transport is classified into passive and active, determined by the energy requirement. Unlike passive transport, which allows molecules to move down their concentration gradient without energy input, active transport requires the direct or indirect expenditure of cellular energy, typically adenosine triphosphate (ATP). This process allows a cell to accumulate necessary substances like ions, amino acids, and glucose at concentrations greater than those found externally, maintaining the distinct internal chemical balance required for life.
The Engine of the Cell: Primary Active Transport
Primary active transport uses the direct energy from ATP hydrolysis to move substances across the membrane. The Sodium-Potassium Pump (Na+/K+-ATPase), an enzyme embedded in the plasma membrane of animal cells, is the primary example. This transport protein maintains the ionic concentrations of sodium and potassium between the cell interior and exterior by binding three sodium ions (Na+) from inside the cell and two potassium ions (K+) from outside.
Once the sodium ions and an ATP molecule are bound, the pump hydrolyzes the ATP, transferring a phosphate group to the protein. This phosphorylation causes a conformational change, opening the pump to the outside and reducing its affinity for sodium ions, which are then released. The new shape increases the pump’s affinity for potassium ions, allowing two K+ ions to bind from the exterior.
The binding of potassium triggers the release of the phosphate group, causing the pump to revert to its original conformation, opening to the cell’s interior. This change lowers the affinity for potassium, releasing the two K+ ions into the cytoplasm, restarting the cycle. The net result is the export of three positive charges (Na+) and the import of two positive charges (K+) for every molecule of ATP consumed.
This movement of charge establishes the resting membrane potential, making the cell interior slightly negative compared to the exterior. The Na+/K+ pump is responsible for nearly one-third of the cell’s total energy expenditure, maintaining the electrochemical gradient necessary for nerve impulse transmission and muscle contraction. By exporting sodium ions, the pump regulates cell volume and prevents rupture by helping prevent excessive water accumulation inside the cell.
Secondary Active Transport: Harnessing Concentration Gradients
Secondary active transport utilizes the potential energy stored in the concentration gradient created by primary active transporters, rather than directly consuming ATP. The steep sodium gradient established by the Na+/K+-ATPase provides the driving force. As sodium ions rush back into the cell down their concentration gradient, their movement is coupled to the transport of another molecule moving simultaneously against its own gradient.
Symport
Symport occurs when both the driving ion and the transported substance move in the same direction across the membrane. The Sodium-Glucose Linked Transporter 1 (SGLT1), found in the small intestine and kidney tubules, is a common example. This transporter couples the downhill movement of two sodium ions into the cell with the uphill movement of one glucose molecule.
Antiport
Antiport occurs when the driving ion moves in one direction while the transported molecule moves in the opposite direction. The sodium-calcium exchanger (NCX), a protein in cardiac muscle cells, is an example. This antiporter uses the energy from three sodium ions flowing into the cell to expel one calcium ion from the cell interior.
Active Transport in Specialized Biological Systems
Active transport mechanisms are adapted for specialized functions in various biological systems. Proton pumps are primary active transporters that use ATP to move hydrogen ions (protons) into certain organelles. These pumps create the acidic environment within lysosomes, which is required for digestive enzymes to break down waste materials and cellular debris.
In plants, active transport is used for nutrient acquisition from the soil, where mineral ion concentrations are often low. Root hair cells utilize proton pumps to actively move H+ ions out of the cell and into the soil. This proton efflux establishes an electrochemical gradient across the root hair membrane, which drives the uptake of essential ions like nitrates and phosphates against their concentration gradients.
In mitochondria and chloroplasts, electron transport chains utilize proton pumps to establish a high concentration of H+ ions in the intermembrane space or thylakoid lumen. This proton gradient represents a stored form of energy, known as the proton motive force, which is harnessed by the ATP synthase enzyme to generate the vast majority of the cell’s ATP supply.
Active Transport and Human Health
Active transport is frequently involved in human disease and targeted by therapeutic drugs. Cystic Fibrosis is an example caused by a defect in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), a chloride channel that uses ATP binding to regulate ion flow. A non-functional CFTR protein disrupts the movement of chloride ions and subsequent water flow across epithelial membranes, leading to characteristic thick, sticky mucus in the lungs and digestive tract.
Medications often manipulate specific active transporters for therapeutic effects. For instance, heart failure drugs like digitalis inhibit the Na+/K+ pump in cardiac muscle cells, indirectly leading to a rise in intracellular calcium that strengthens heart contractions. Diabetes drugs called SGLT2 inhibitors target the SGLT2 symporter in the kidney tubules. By blocking this secondary active transporter, the drugs prevent the reabsorption of glucose, causing it to be excreted in the urine and lowering blood sugar levels in patients with Type 2 diabetes.