MEMBRANE TRANSPORT 

As we have seen from the consideration of passive processes, many important substances are able to cross the plasma membrane by variations on the diffusion theme. Of course one of the basic tenets of diffusion is that the substance can only move down its concentration gradient. However many physiological processes require substances to move from a region of low concentration to one of high concentration (i.e. against the concentration gradient). For this reason these processes require the use of cellular energy and are therefore referred to as active processes. There are a number of these active processes which we will now consider.

A. ACTIVE TRANSPORT (or Solute Pumping)

In active transport a membrane protein acts as a molecular pump to move substances such as Na⁺, K⁺, Ca²⁺, some sugars and most amino acids across the membrane. In most instances the protein pump has a high affinity binding site for a particular substance on the low concentration side of the membrane. After the substance binds, the protein undergoes a conformational change which results in the transfer of the substance to the opposite side of the membrane where it is released. The process is usually powered by ATP and in some instances may move more than one substance at a time. Examples of active transport include the hydrogen ion pump, the sodium-potassium exchange pump and the calcium pump. Note that whilst small water-soluble ions can pass through the membrane by simple diffusion (as discussed previously) they can also be transported by solute pumping when they have to move against their concentration gradient. The important point here is that substances can be transferred by one, two or more transport mechanisms depending upon the nature of the cell, the physiological process it is involved in and the concentration gradient of the substance across the membrane.

B. BULK TRANSPORT Large substances such as macromolecules produced by cells are unable to traverse the plasma membrane by any of the processes considered so far. They are simply too large for diffusion or to be effectively transported by a solute pump. Instead these substance enter or leave cells enclosed in membrane-bound vesicles and the process is powered by ATP. There are two types of bulk transport which are named according to which direction the substances are moving across the membrane: (i) Exocytosis In this instance hormones, neurotransmitters, enzymes and other macromolecules that are synthesised within the cell and stored in intracellular membrane-bound vesicles are secreted into the extracellular space. If we take a more detailed look at these vesicles we can see that exocytosis involves migration of the vesicle to the plasma membrane with which it then fuses . The plasma membrane adjacent to the vesicle then breaks down and the contents are released into the extracellular space.

(ii) Endocytosis

Endocytosis is essentially the reverse of exocytosis and involves the transfer of large particles, macromolecules and extracellular fluid INTO the cell. The process involves a fold of the plasma membrane forming around the substance to be ingested which then goes on to form a membrane-bound vesicle. There are three variations on this basic theme which differ according to the nature of the substance being ingested:

(a) Phagocytosis: A few specialised cells (most notable macrophages and some white blood cells) are able to ingest relatively large solid particles (such as cellular debris) by a process referred to as phagocytosis. This process involves extension of a portion of the plasma membrane around the particle and then fusion of these extensions to form a particle-containing vesicle (referred to as a phagosome) . In most instances the phagosome then fuses with a lysosome which contains digestive enzymes. These enzymes break down the ingested debris and subsequently release the products into the cell's cytoplasm. For this reason phagocytosis is analogous to cell "eating". (b) Pinocytosis: Unlike phagocytosis, most cells in the body perform pinocytosis which simply involves a small volume of the extracellular fluid being incorporated into a membrane-bound vesicle formed by a small fold in the plasma membrane . (c) Receptor-mediated Endocytosis: Both phagocytosis and pinocytosis are relatively non-specific in terms of the substances which are ingested. Receptor-mediated endocytosis on the other hand is a much more selective form of bulk transport because the membrane expresses extracellular receptors to which a particular macromolecule binds. This then triggers endocytosis of the portion of the membrane containing the receptor/macromolecule complex . Substances which are carried into cells in this manner include cholesterol, iron and the hormone insulin.

One interesting consequence of these mechanisms of bulk transport is that portions of the cell membrane are constantly being removed by endocytosis and subsequently replaced by exocytosis. The mechanisms by which cells monitor this have not yet been determined but it is clearly an important consideration if the cell is to maintain its functional integrity.