Biologists in nearly every field of study have discovered that one of the major methods by which organisms regulate their metabolisms is by controlling the movement of molecules into cells or into organelles such as the nucleus.
This regulation is possible because of the semipermeable nature of cellular membranes. The membranes of all living cells are fluid mosaic structures composed primarily of lipids and proteins. The lipid molecules are aliphatic, which means that their molecular structure exhibits both a hydrophilic (water-attracted) and a hydrophobic (water-repelling) portion.
These aliphatic molecules form a double layer: The hydrophilic heads are arranged opposite one another on the inner and outer surfaces, and the hydrophobic tails are aligned across from one another within the interior, sandwiched between the hydrophilic heads. The protein in the membrane is interspersed periodically throughout the lipid bilayer.
Some of the protein, referred to as peripheral protein, penetrates only one of the lipid layers. The integral protein, as the remaining protein is called, extends through both layers of lipid to interface with the environment on both the internal and external surfaces of the membrane. These integral proteins can serve as transport channels and carriers.
Transport across the membrane is accomplished by three different mechanisms: simple diffusion, facilitated diffusion, and active transport. The first two mechanisms are referred to as passive processes because they do not require the direct input of cellular energy, and they involve transport down a concentration gradient, that is, from the side with a higher concentration to the side with a lower concentration of the substance being transported.
In many instances, however, substances are transported across a membrane from the side with a low concentration to the side containing a greater concentration. This "uphill" movement across membranes is called active transport, and it requires the expenditure of cellular energy.
Cellular energy, produced by the biological oxidation of fuels such as carbohydrates, is stored as adenosine triphosphate (ATP). When this high-energy phosphate is hydrolyzed, the stored energy is released to drive cellular reactions such as active transport. The ATPase protein located in membranes belongs to one of the groups of enzymes which hydrolyze ATP.
The mechanism has not been completely deciphered, but it appears as though a protein carrier molecule binds with the substance to be transported at the surface on one side of the membrane. This binding occurs at a specific activated region on the carrier protein called the active site. After combining with the carrier, the substance is moved across the membrane and released at the surface on the other side of the membrane.
ATP is then hydrolyzed by an ATPase, and the energy released in this reaction prepares the protein carrier for attachment to another molecule to be transported by reactivating the active site. There is some question as to whether ATPase is a component of the carrier molecule or functions separately from it. Regardless of the spatial arrangement, the two molecules are intimately related in the active transport process.
Cotransport and Countertransport
There are two important modifications of the active transport process: cotransport and countertransport. Cotransport, or symport, involves a specialized protein molecule referred to as a symport carrier. Asymport carrier has two attachment sites. One site is for the attachment of the molecule to be transported, and the other is for the attachment of a second molecule, which can be referred to as the synergist.
Both the molecule to be transported and the synergist must be bound to the symport carrier before transport across the membrane can take place. The synergist is moved down a concentration gradient, and this downhill flow of the synergist drives the carrier to transport both molecules.
In order to keep the synergist moving down a concentration gradient when attached to the symport carrier, the synergist must be pumped back across the membrane. This movement of the synergist in the opposite direction is mediated by a protein carrier activated by the energy released from the hydrolysis of ATP by an ATPase.
Countertransport, or antiport, also utilizes a specialized carrier with two attachment sites. This antiport carrier binds with the molecule to be transported at one of the attachment sites, and a second molecule, which can be called the antagonist, binds at the other.
The carrier moves the molecule to be transported across the membrane while simultaneously moving the antagonist in the opposite direction. Again, both molecules must be attached to the antiport carrier before either can be transported, and the flow of the antagonist down a concentration gradient drives the transport by the carrier in both directions.
The antagonist is pumped back across the membrane by a protein carrier activated by the energy released from the hydrolytic action of an ATPase on ATP. This action maintains a concentration gradient favorable for transport when the antagonist is attached to the antiport carrier.
Transport in Action
The presence of these three active transport mechanisms has been well documented. Calcium, for example, has been shown to be pumped from the cell by a carrier protein activated by the hydrolysis of ATP. Sugars for energy and carbohydrate structure must be cotransported into the cell by a symport carrier that utilizes the sodium ion as a synergist. At least two countertransport ion pumps have been identified.
One pumps the potassium ion into the cell at the same time that it pumps the hydrogen ion out. The second pumps the potassium ion into the cell while the antagonist, sodium, is moved in the opposite direction. It is likely that numerous other active transport systems exist that have not yet been positively identified.
A protein carrier is one of the basic components of any active transport mechanism. Although no specific carrier molecule has yet been positively identified, there is ample indirect evidence to support the presence of such a protein. Much of this evidence comes from studies showing that active transport exhibits saturation kinetics.
This means that the transport of a specific ion will increase as the concentration increases, up to a certain point. At this point, further increases in concentration will have no effect on transport. These results strongly suggest that the ion is binding with another molecule in the membrane, such as a carrier protein, which is limited in concentration and becomes saturated.
Studies have also shown the transport of some substances to be competitively inhibited by the presence of another, very similar, substance. This indicates that both substances are competing for the same site on a membrane molecule, such as a protein carrier.
Role of Active Transport
The ability to accumulate substances against a concentration gradient is necessary for the normal function and survival of cells. There are numerous examples, however, of active transport being intimately involved in the regulation of some important biological processes. In the plant kingdom, sugar is produced by photosynthesis in the green leaves.
This sugar must be transported out of the leaves and into nonphotosynthetic tissues, such as roots or fruit, through specialized transport cells in the phloem. The loading of sugars into the phloem is dependent on an active cotransport mechanism.
Almost every field of life science is concerned with gene regulation. Genes are continually being induced (activated) or repressed (deactivated) as organisms develop and change from the time of their conception until their death.
Repression is usually caused by the presence of a protein molecule in the cell nucleus, but induction may very often be the result of metabolites being actively transported into the cell or nucleus. Hence, the active transport mechanisms may be a very important component of gene regulation.