Primary and Secondary Active Transport

The active transport of molecules across cell membranes is one of the major factors on molecular level for keeping homeostasis within the body. Primary active transport is the process in which metabolic energy is directly used by membrane proteins to transport molecules. Secondary active transport is based on the accrued concentration gradient of molecules from the primary active transport and its tendency to equilibrate concentration. This movement is utilised by transport proteins to transport other molecules against their concentration gradients (Symporters, see below).

Cell Membrane

The cell membrane consists of a lipid bilayer including a large amount of protein molecules. These are considered as integral or peripheral membrane proteins. The lipid bilayer constitutes a barrier for the movement of different substances. However, some substances, especially lipid-soluble substances, are still able to pass this lipid bilayer through diffusion. The membrane proteins show different properties for the transport of substances. Their molecular structures interrupt the continuity of the lipid bilayer and thereby constitute an alternative pathway through the cell membrane. Hence the vast majority of the membrane proteins are regarded as transport proteins. They play a crucial role in keeping the ion concentration on a physiological level. The way how transportation is achieved differs among three groups of transport proteins.


 * Large pores, consisting of several protein subunits, that allow the bulk flow of water, ions and larger molecules down their chemical concentration gradients (facilitated diffusion). No additional metabolic activity is required hereby.


 * ATP-dependent ion pumps is the usage of direct or indirect metabolic energy to move molecules against its electrochemical gradient.


 * Specialized ion channels that only allow the passage of particular ions across the membrane.

Those proteins are either


 * Uniporters, that move one type of molecule in one direction


 * Symporters, that move several molecules in one direction


 * Antiporters, that move different molecules in opposite directions.

The main feature of the ATP-dependent ion pumps certainly is the energy-demanding transport and all of its functions. These proteins bind and transport molecules or ions whose movement is directed against their electrochemical concentration gradient. Additional energy is required to set up this so called active transport. At times, a large concentration of a substance is required in the intracellular fluid even though the extracellular fluid contains only a small concentration. This is true for potassium ions; in some instances it is important to keep the concentration of other ions very low inside the cell even though their concentrations in the extracellular fluid are great, this is true for sodium ions. This cannot occur by diffusion through the cell membrane, because simple diffusion equilibrates the concentrations on the two sides of the membranes.



Active Transport

Active transport is divided into two types according to the source of energy used, called primary active transport and secondary active transport. In primary active transport, the energy is derived directly from the breakdown of ATP. In the secondary active transport, the energy is derived secondarily from energy that has been stored in the form of ionic concentration differences between the two sides of a membrane.

Primary Active Transport

Example: Sodium-Potassium Pump

Substances that are transported by primary active transport are sodium, potassium, calcium, hydrogen, chloride and also a few other ions. The active transport mechanism that has been studied the most and is of most importance is the sodium-potassium Na/K Pump (Nobel Prize in Chemistry 1997). The sodium-potassium pump is a transport process that pumps sodium ions outward through the cell membrane and at the same time pumps potassium ions from the outside to the inside (Antiporter, see above). This pump is vital and responsible for maintaining the sodium and potassium concentration differences across the cell membrane and also for establishing a negative electrical voltage inside the cells. This pump is the basis of nerve function for transmitting nerve signals throughout the nervous system. The pump is composed of the carrier protein which is a complex of two separate globular proteins, a larger one, the alpha subunit and a smaller one, the beta subunit. There are three main functions of the beta subunit.


 * It has three receptor sites for binding sodium ions on the inside


 * It has two receptor sites for potassium ions on the outside


 * The inside portion of this protein near to the sodium binding sites has ATPase activity.

When two potassium ions bind on the outside of the carrier protein and three sodium ions bind on the inside, the ATPase function of the protein becomes activated. This cleaves the molecule of ATP, splicing it in to ADP and thus liberates energy. This energy then creates a change in the protein carrier molecule, extruding the three sodium ions to the outside and the two potassium to the inside. The sodium-potassium pump can also run in reverse, depending on the electrochemical concentration gradients for sodium and potassium. So if the stored energy of these gradients exceed the chemical energy released by the ATP hydrolysis the ions will move down their concentration gradients  and the pump will synthesize ATP from ADP and phosphate.



Secondary Active Transport

When sodium ions are transported out of cells by primary active transport, a large concentration gradient develops: a high extracellular concentration of 142 mEql/L and low intracellular concentration of 10 mEql/L respectively. This gradient represents a storehouse of energy because the excess sodium on the outside have the tendency to go back to the inside. Transporters found in the kidney tubules transport glucose and amino acids against its concentration gradient with the energy released by back-flowing Sodium ions.

Function

The most important function of the sodium-potassium pump is to control the volume of the cells. Without this function of the pump, most cells in the body would swell until they burst. This mechanisms is based on the fact that inside the cell are a large number of proteins and other organic compounds that cannot escape. These are mostly negatively charged and therefore attract  positive ions. This causes osmosis of water inside and thus the swelling of the cell. The sodium-potassium pump is preventing this to happen. The pump establishes a continual net loss of ions to the outside of the cell, which initiates the movement of water towards the extracellular fluid, too.

References

Physiology at a Glance 2nd edition by Jeremy Ward & Roger Linden

Medical Physiology 11th edition by Guyton and Hall