In primary active transport, energy from ATP is directly used to transport molecules against their concentration gradient. For example, the Na+/K+-ATPase is a membrane spanning protein carrier. Please note the –ase ending, so it is also an enzyme that hydrolyzes (breaks bonds with water) ATP to get its energy. It is also referred to as the ‘Na+/K+ pump’. This is because it acts much like a pump that is bailing out a leaky ship. It works non-stop to continuously expel 3 Na+ ions out of the cell and at the same time import 2 K+ ions into the cell per cycle. Each cycle of the pump requires 1 ATP molecule. Both Na+ and K+ are being moved against their concentration gradients, therefore we know that ATP must be required because this is active transport. The ATP is hydrolyzed to ADP + Pi + Energy! This is an antiport mechanism, as both molecules are being transported in opposite directions. The Na+/K+ pump helps to maintain the resting membrane potential (RMP) across the plasma membrane of all living cells. Draw a diagram of the Na+/K+ pump.
2) Secondary active transport (indirect)
In secondary active transport, the ATP is used indirectly to move molecules across membranes. Essentially what this means is the potential energy that is stored in a concentration gradient is used to help move molecules across a membrane. An excellent illustration of how this is done is seen in the Na+/glucose transporter. The relative concentration of Na+ is low on the inside, high on the outside of the cell. When Na+ moves down its concentration gradient (into the cell) this force is harnessed to move glucose against its concentration gradient (also into the cell). While the Na+ goes down its gradient, the glucose can be dragged along with it, up hill, so to speak. The original source of ATP that allows this to occur is the one used in the Na+/K+ pump described above, as it maintains a low Na+ concentration inside the cell. This is a symport mechanism, as both molecules are being transported in the same direction. Draw a diagram of the Na+/glucose transporter.
3) Vesicular Transport
Vesicular transport is used to move large macromolecules or large quantities of a molecule across the plasma membrane. Vesicles are like mini lipid bilayer bubbles that bud off from plasma membrane and encapsulate large molecules. This is an active form of transport that directly requires energy in the form of ATP for the maneuvering of the cytoskeleton.
There are two main forms of Vesicular transport
- Endocytosis – bringing material into the cell, inward vesicular transport.
- Exocytosis – releasing material from the cell, outward vesicular transport.
- Endocytosis: There are three general kinds of endocytosis.
1) Pinocytosis (cell drinking): relatively unselective whereby ECF is transported into the cell.
2) Phagocytosis is a process by which cells engulf a particle or another cell into a much larger vesicle, e.g., certain types of WBC (called Macrophages) engulf bacteria this way.
3) Receptor-Mediated Endocytosis: This is a very selective process. Receptors on the external surface of the plasma membrane bind specific ligands. This ligand-receptor complex then creates a clathrin-coated pit, a type of invagination of the membrane. The membrane then pinches this off as cytoplasmic vesicle, thereby ingesting the ligand-receptor complexes. The vesicle membrane and the receptors are recycled to the surface membrane to be used again.
- Exocytosis: This is used by many cells to secrete or release large molecules or large amounts of a molecule. Intracellular vesicles fuse with the plasma membrane, then releases its contents into ECF. This process requires energy and Ca2+ and involves other proteins. An excellent example of how this is commonly used in the body is the release of neurotransmitters from neurons into the synaptic cleft. This process is also used to secrete large lipophobic molecules, such as hormones, protein fibers and mucus across cell membranes. Exocytosis is also used to insert proteins, such as receptors, into membrane. Lysosomes can remove waste in this manner and is often regulated from outside of the cell (e.g., hormone-induced hormone release).
Transcytosis and Vesicular Transport
Transcytosis means movement across (trans) a cell (cytosis); it can involve endocytosis, then vesicular transport across cell, then exocytosis out of the cell at the other end. So the substance has moved completely across the cell. This provides for movement of large proteins intact, e.g., the absorption of maternal antibodies through breast milk, or the movement of proteins across capillary endothelium.
Transport Across Epithelial Linings
An excellent summary of the various types of transport discussed so far is the transport of molecules across epithelial linings, called transepithelial movement. Epithelial membranes are polarized with an apical (lumen or top side) and basolateral (ECF side) membranes have different proteins. The Na+-glucose symport on apical membrane and the Na+-K+-ATPase is only on basolateral (bottom side) membrane. Transporting epithelial cells can alter their permeability by inserting or withdrawing membrane proteins.
Although glucose is a large polar molecule (and thus has 2 strikes against it for having an easy passage across a membrane), there are two different transport systems to move glucose across epithelial cells:
- Secondary active transport. The Na+/glucose symport from the lumen of the gut into the cell through the apical membrane. This is made possible by the continuous active transport of Na+, constantly being ejected across the basolateral membrane of the cell via Na+-K+-ATPase.
- Glucose can also move across a membrane down its concentration gradient by facilitated diffusion, as seen in across basolateral membrane of the cell.
As an interesting note, the substance ouabain, a known powerful toxin to cells, specifically inhibits the Na+/K+-ATPase. These Na+/K+ pumps are found only on the basolateral membrane of transporting epithelial cells. Ouabain placed on one side of the epithelium affects only that side, so only when ouabain is applied to the basolateral side will cause glucose transport to decrease slowly, as the Na+ gradient is abolished, because Na+ enters the apical side with glucose but is not pumped out, so over time the Na+ gradient that powers the symporter disappears.