Transport of Substances Through the Cell Membrane “Diffusion” Versus “Active Transport.”

Transport of Substances Through the Cell Membrane “Diffusion” Versus “Active Transport.”

 Transport through the cell membrane, either directly through the lipid bilayer or through the proteins, occurs by one of two  basic processes:

(1) Diffusion.

(2) Active transport.

Diffusion:  means random molecular movement of substances molecule by molecule, either  through  intermolecular spaces in the membrane or in combination with a carrier  protein. 

Active transport:  means movement of  ions or other substances across the membrane in combination  with a carrier protein in such a

way that the carrier protein causes the substance to move against  an energy gradient, such as from a low-concentration state to a high-concentration state. This movement  requires an additional source of energy besides kinetic energy.

Diffusion Through the Cell Membrane

Simple diffusion and facilitated diffusion.

 Simple diffusion:  Means that kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without any interaction  with  carrier proteins in the membrane. The rate of diffusion is determined by the amount of  substance available, the velocity of kinetic motion, and the number and sizes of openings in the membrane through which the molecules or ions can move. Simple diffusion can occur through the cell membrane by two pathways:

 (1) Through the interstices of the lipid  bilayer if the diffusing substance is lipid soluble.

(2) Through watery channels that penetrate all the way through some of the large transport  proteins.

 Facilitated diffusion:

 Requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them and shuttling them through the membrane in this form.

Diffusion of Lipid-Soluble Substances Through the Lipid Bilayer.

One of the most important factors that determines how rapidly a substance diffuses through the lipid  bilayer is the lipid solubility of the substance. For instance, the lipid solubilities of oxygen, nitrogen, carbon dioxide, and alcohols are high, so that all these can dissolve directly in the lipid bilayer and diffuse through the cell membrane in the same manner that diffusion of water solutes occurs in a watery solution.

Diffusion of Water and Other Lipid-Insoluble Molecules Through Protein Channels.

 Even though water is highly insoluble in the membrane lipids, it readily passes through channels  in protein molecules that penetrate all the way  through the membrane.  Other lipid-insoluble molecules can pass through  the protein pore channels in the same way as water  molecules if they are water soluble and small enough.

Diffusion Through Protein Channels, and “Gating” of These Channels:

Substances can move by simple diffusion directly along these channels from one side of the membrane to the other. The protein channels are distinguished by two important characteristics:

(1)  They are often selectively permeable to certain substances.

 (2) Many of the channels can be opened or closed by gates.

Selective Permeability of Protein Channels.

 Many of the protein channels are highly selective for transport of one or more specific ions or molecules. This results from the characteristics of the channel itself, such as  its diameter, its shape, and the nature of the electrical  charges and chemical bonds along its inside surfaces. To give an example, one of the most important of the protein channels:

Sodium channels:  They are  only 0.3 by 0.5 nanometer in diameter,  the inner surfaces of this channel are strongly negatively  charged. These strong negative charges can pull small dehydrated  sodium ions into these channels, actually pulling  the sodium ions away from their hydrating water molecules. Thus, the sodium channel is specifically selective for passage of sodium ions.

 Potassium channels:  These channels are slightly smaller than the sodium channels, only 0.3 by 0.3 nanometer, but  they are not negatively charged, and their chemical bonds are different. Therefore, no strong attractive force is pulling ions into the channels, and the potassium ions are not pulled away from the water molecules that hydrate them.

The hydrated form of the potassium ion is considerably smaller than the hydrated form of sodium because the sodium ion attracts far more water molecules than does potassium. Therefore, the smaller hydrated potassium ions can pass easily through this small channel, whereas the larger hydrated sodium ions are rejected, thus providing selective permeability for a specific ion.

Gating of Protein Channels.

Gating of protein channels provides a means of controlling ion permeability of the channels. It is believed that some of the gates are actual gate like extensions of the transport protein molecule, which can close the opening of the channel or can be lifted away from the opening by a conformational change in the shape of the protein molecule itself. The opening and closing of gates are controlled in  two principal ways:

1.              Voltage  gating.

when there is a strong negative charge  on the inside of the cell membrane, this presumably  could  cause the outside sodium gates to remain tightly closed; conversely, when the inside of the membrane loses its negative charge, these gates would open suddenly and allow tremendous quantities of sodium to pass inward through the sodium pores. This is the basic mechanism for eliciting action potentials in nerves that are responsible for nerve signals. While  the potassium gates are on the  intracellular ends of the potassium channels, and  they open when the inside of the cell membrane  becomes positively charged. The opening of these  gates is partly responsible for terminating the  action potential.

2. Chemical (ligand) gating.

Some protein channel  gates are opened by the binding of a chemical substance (a ligand) with the protein; this causes a conformational or chemical bonding change in the protein molecule that opens or closes the gate. This is called chemical gating or ligand gating. One of the most important instances of chemical gating is the effect of acetylcholine on the so-called  acetylcholine channel.  Among the most important substances that cross  cell membranes by facilitated diffusion are glucose and most of the amino acids. In the case of glucose, the carrier molecule has been discovered, and it has a molecular weight of about 45,000; it can also transport several other monosaccharides that have structures  similar to that of glucose, including  galactose. Also, insulin can increase the rate of  facilitated diffusion of  glucose as much as 10-fold to 20-fold. This is the principal  mechanism by which insulin controls glucose use  in the body.

Factors That Affect Net Rate of Diffusion:

(1) Concentration Difference : The rate at which the substance diffuses inward is proportional to the concentration of   molecules   on   the

outside, because this  concentration determines how many molecules strike the outside of the membrane each second.Conversely, the rate at which molecules diffuse outward is proportional to their concentration inside the membrane.  Therefore,  the rate of net diffusion into the cell is proportional to the concentration on the outside minus the concentration  on the inside,   or:   Net  diffusion  μ (Co - Ci)   in which Co is concentration outside and Ci  is concentration inside.

(2) Membrane Electrical Potential. If an electrical potential is applied across the membrane, the electrical charges of the ions cause them to move through the membrane even though no concentration difference exists to cause movement.

(3)  Effect of a Pressure Difference Across the Membrane.  Considerable pressure difference develops between the two sides of a diffusible membrane. This occurs, for instance, at the blood capillary membrane in all tissues of the body. The pressure is about 20 mm Hg greater inside the capillary than outside.

“Active Transport” of Substances Through Membranes:                    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 instance, for potassium ions.

Conversely, it is important to keep the concentrations of other ions very low inside the cell even though their concentrations in the extracellular fluid are great. This is especially true for sodium ions. Different substances that are actively transported through at least some cell membranes include sodium ions, potassium ions, calcium ions, iron ions, hydrogen ions, chloride ions, iodide ions, urate ions, several different sugars, and most of the amino acids.

Primary Active Transport  Sodium-Potassium Pump

Sodium-potassium (Na+-K+) pump, a transport process that pumps

sodium ions outward through the cell membrane of all cells and at the same time pumps potassium ions from the outside to the inside. This pump is responsible for maintaining the sodium and potassium concentration  differences   across  the  cell  membrane,   as well as for

establishing a negative electrical voltage inside the cells.

The carrier protein is a complex of two separate globular proteins: a larger one called the (a) subunit, with a molecular weight of about 100,000,  and a smaller one called the( b) subunit, with a molecular weight of about 55,000. Although the function of the smaller protein is not known (except that it might anchor the protein complex in the lipid membrane), the larger protein has three specific features that are important for the functioning of the pump:

1. It has three receptor sites for binding sodium ions on the portion of the protein that protrudes to the inside of the cell.

2. It has two receptor sites for potassium ions on the outside.

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

To put the pump into perspective: 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 then  cleaves

one molecule of ATP, splitting it to adenosine  diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the  three sodium ions to the outside and the two potassium ions to the inside. As with other enzymes, the Na+-K+ ATPase pump can run in reverse.

Importance of the Na+-K+ Pump for Controlling Cell Volume.

One of the most important functions of the Na+-K+  pump is to control the volume of each cell. Without  function of this pump, most cells of the body would  swell until they burst. The mechanism for controlling the volume is as follows:

 Inside the cell are large  numbers of proteins and other organic molecules that  cannot escape from the cell. Most of these are negatively  charged and therefore attract large numbers of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis of water to the interior of the cell. Unless this is checked, the  cell will swell indefinitely until it bursts. The normal  mechanism for preventing this is the Na+-K+ pump.  Note  again that this device pumps three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior.

Electrogenic Nature of the Na+-K+ Pump.

The fact that the Na+-K+ pump moves three Na+ ions to the exterior for

every two K+ ions to the interior means that a net of one positive charge is moved from the interior of the cell to the exterior for each cycle of the pump.This creates positivity outside the cell but leaves a deficit of positive ions inside the cell; that is, it causes negativity on the inside. Primary Active Transport of Calcium Ions

 Calcium ions are normally maintained at extremely low concentration in the intracellular cytosol of virtually all cells in the body, at  a concentration about 10,000 times less than that in the  extracellular fluid. This is achieved mainly by two  primary active transport calcium pumps. One is in the  cell membrane and pumps calcium to the outside of the cell. The other pumps calcium ions into one or  more of the intracellular vesicular organelles of the cell, such as the sarcoplasmic reticulum of muscle cells and the mitochondria in all cells. In each of these instances, the carrier protein penetrates the membrane and functions as an enzyme ATPase, having the same capability to cleave ATP as the ATPase of the sodium carrier protein. The difference is that this protein has  a highly specific binding site for calcium instead of for sodium.

Primary Active Transport of Hydrogen Ions                                       At  two places in the body, primary active transport of  hydrogen ions is very important:  in the gastric  glands of the stomach  and  in the late distal tubules and cortical collecting ducts of the kidneys.

Secondary Active Transport— Co-Transport  and Counter Transport

When sodium ions are transported out of cells by primary active transport, a large concentration gradient of sodium ions across the cell membrane usually develops—high concentration outside the cell and

very low concentration inside. This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is always attempting to diffuse to the interior. Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. This phenomenon is called co-transport; it is one form of secondary active transport. For sodium to pull another substance along with it, a coupling mechanism is required. This is achieved by means of still another carrier protein in the cell membrane.

The carrier in this instance serves as an attachment point for both the sodium ion and the substance to be co-transported. Once they both are attached, the  energy gradient of the sodium ion causes both the sodium ion and the other substance to be transported together to the interior of the cell.

 In counter-transport, sodium ions again attempt to  diffuse to the interior of the cell because of their large  concentration gradient. However, this time, the substance  to be transported is on the inside of the cell and must be transported to the outside. Therefore, the  sodium ion binds to the carrier protein where it projects  to the exterior surface of the membrane, while the substance to be counter-transported binds to the interior projection of the carrier protein. Once both have bound, a conformational change occurs, and energy released by the sodium ion moving to the interior causes the other substance to move to the exterior.

Co-Transport of Glucose and Amino Acids  Along with Sodium Ions Glucose and many amino acids are transported into  most cells against large concentration gradients; the mechanism of this is entirely by co-

Fig. Postulated mechanism for sodium co-transport of glucose

transport, the transport carrier protein has two binding sites on its exterior side, one for sodium and one for glucose. Also, the concentration of   sodium ions is very high on the outside and very low  inside, which provides energy for the transport.  A special  property of the transport protein is that a conformational  change to allow sodium movement to the 

interior will not occur until a glucose molecule also  attaches. When they both become attached, the conformational  change takes place, and the sodium and glucose are transported to the inside of the cell at the same time. Hence, this is a sodium-glucose  co-transport mechanism.

Sodium co-transport of the amino acids occurs in the same manner as for glucose, except that it uses a different set of transport proteins.

 Other important co-transport mechanisms include co-transport of chloride ions, iodine ions, iron ions, and urate ions.

Sodium Counter-Transport of Calcium and  Hydrogen Ions

Sodium-calcium counter-transport occurs through all or almost all cell membranes, with sodium  ions  moving to the interior and calcium ions to the exterior.

 Sodium-hydrogen counter-transport occurs  in  the proximal tubules of the kidneys.

Active Transport Through Cellular Sheets:                                          At many places in the body, substances must be transported all the way through a cellular sheet instead of  simply through the cell membrane. Transport of this  type occurs through the:

Intestinal epithelium.

Epithelium of the renal tubules.

Epithelium of the gallbladder.

Membrane of the choroid plexus of the brain and other membranes.

 The basic mechanism for transport of a substance  through a cellular sheet is:

 (1) Active transport through the cell membrane on one side of the transporting cells in the sheet.

 (2)  Simple diffusion or  facilitated diffusion through the membrane on the opposite side of the cell.

The  epithelial cells are connected together  tightly at the luminal pole by means of junctions called “kisses.” The  brush border on the luminal surfaces of the cells is permeable to both sodium ions and water. Therefore, sodium and water diffuse readily from the lumen into the interior of the cell. Then, at the basal and lateral membranes of the cells, sodium ions are  actively transported into the extracellular fluid of  the surrounding connective tissue and blood vessels. This creates a high sodium ion concentration gradient  across these membranes, which in turn causes osmosis of water as well. Thus, active transport of sodium ions  at the  basolateral  sides of the epithelial cells results in  transport not only of sodium ions but also of water. These are the mechanisms by which almost all the  nutrients, ions, and other substances are absorbed into  the blood from the intestine; they are also the way by which  the  same substances are reabsorbed from the glomerular filtrate by the renal tubules.

Fig: Basic mechanism of active transport across a layer of cells.