Discuss the various mechanisms that operate to transport molecules across biological membranes.
Transportation of molecules across biological membranes is required due to plasma membranes which have the basic function of separation between cells and intracellular organelles, which compartmentalise different functions within the cell, defining these various organelles. Whilst the main function of biological membranes is to physically separate two functions of the cell, transportation of various molecules across these membranes is required to allow for the continuation of many biological processes that occur both within and outside of the cell. Plasma membranes are composed of phospholipid bilayers which allow the membrane to be selectively permeable, to control the movement of molecules between the cytoplasmic and exoplasmic sides of organelles and cells (figure 1) This transportation of solutes is regulated by proteins within the membrane.
Figure 1 – The fluid mosaic model of plasma membranes, showing the overall structural features including the phospholipid bilayer, and typical glycolipids, sterols and proteins that exist within the membrane.
Passive transport
Passive transport is the net movement along the gradient from an area of high concentration to one of low concentration and so does not require energy. However, the continual movement of these molecules into and out of cells is required to prevent equilibrium being reached within the cell, to maintain the gradient by which the molecules move down.
Simple diffusion
Passive transport can occur by simple diffusion where no membrane proteins are involved as the gradient occurs directly across the cell membrane as the solutes are lipid soluble and are not polar and so can travel across the phospholipid bilayers. Molecules that are transported this way include small, uncharged molecules and gases – e.g. carbon dioxide, oxygen, and urea. Here, the rate of transport is proportional to the solute concentration.
Facilitated diffusion
Passive transport of large molecules, e.g. amino acids, glucose and other nutrients, occurs by facilitated diffusion via transport proteins in the membrane. These substances require specific transporters to identify and enable their movement.
Facilitated diffusion along carrier proteins
Carrier proteins transport almost all small organic molecules and require an interaction of the solute and the binding site of the carrier protein in order the protein to change shape and allow for the movement of the solute into the cell. This means that the process is very selective and therefore very slow, moving less than 1000 molecules per second. An example of this would be the GLuT1 protein which is involved in the co-transport of glucose into the cell.
Facilitated diffusion along channel proteins
There are channel proteins which form pores due to hydrophilic amino acids within the plasma membrane and allow are mostly in charge of transporting ions but also large molecules, and water. These channels show some selectivity by each ion channel being specific to the various ions, e.g. potassium channels, and allow the movement to be very fast, moving more than 107 ions per second. The driving force behind the movement of charged solutes is the electrochemical gradient across a membrane, which separates the difference in concentration between the inside and outside of the cell due to the phospholipid bilayer. An example of this is aquaporins, transmembrane channel proteins which transport water molecules rapidly into kidney cells to allow for urine production. These aquaporins osmosis
Gating of channels
However, the rate of transport is faster initially but reaches the maximal value when the carrier becomes saturated.
Glycoproteins that exist on the plasma membrane can affect the movement of molecules of certain chemicals by identifying to the cell the necessity to incorporate more or less channel or carrier proteins into the membrane to allow for a better equilibrium of substances. For example, insulin on liver cells creating more carrier proteins to transport glucose.
Some solutes can be transported by both simple and facilitated diffusion.
♣ Osmosis
o Diffusion of water molecules across a partially permeable membrane from an area of high water potential to an area of low water potential
o Water molecules can diffuse easily through the cell membrane
o Pure water has a water potential of 0
o Water potential is measured in kPa
o If 2 solutions have the same water potential, they are isotonic
o If the solution has a higher water potential than the cell, it is hypotonic
♣ Cells would increase in size
♣ Red blood cells would burst
♣ Plant cells would be unable to burst due to strong cellulose cell wall
o If the cell has a higher water potential than the solution, it is hypertonic
♣ Cells would shrink
Active transport
Active transport is the movement of a solute against the electrochemical gradient and so requires energy to do so. A specific transmembrane protein carrier is also required to transfer the solute.
What requires active tranport
Primary/direct active transport
Primary or direct active transport is where transmembrane proteins transport solutes against the gradient, using energy produced by the direct hydrolysis of ATP in respiration. One of the most common examples of this transport is sodium-potassium ATPase which Is found in the plasma membranes of all animal cells. This transportation is required to retain the osmotic balance between the inside and outside of the cell. Here, the sodium ions from the exterior of the cell which are in higher in concentration, bind to the carrier pump to travel against their gradient. This triggers the phosphorylation of the subunits of the pump by the ATP molecule leading to a conformational change in the protein, expelling sodium ions into the cell and causes the movement of potassium ions from the inside of the cell, where they are in high concentration, to the pump. This initiates a dephosphorylation of the pump, leading to another conformational change back to the original shape and releases the potassium into the cell. This is the primary mechanism for setting up sodium ion gradients which are required for coupled transport of other substances against their gradients in the majority of transport mechanisms.
Secondary/indirect active transport
Secondary or indirect active transport is also known as coupled transport as one solute travels along the electrochemical gradient, whilst the other solute travels against their gradient. This indirectly uses the energy produced from the hydrolysis of ATP used to set up the sodium electrochemical gradient. The co-transporter proteins that carry out this movement can be either symporters or antiporters. Symporters move both solutes in the same direction, whereas antiporters carry out movement of each solute in opposite directions.
In the transportation of monosaccharides (glucose) from the gut into epithelium cells of the mammalian ileum, two mechanisms of active transport and one of facilitated diffusion are required. The first is using the sodium-glucose symporter. The electrochemical gradient set up by the sodium ions (as stated previously) drives the movement of glucose. Sodium ions are in high concentration in the gut and bind to the pump, initiating the binding of glucose molecules from the gut to the pump as well – both of which are required for the change in shape of the protein. The glucose, however, is travelling against its gradient with this movement. This triggers a conformational change of the protein and both solutes move into the cells. A low concentration of sodium ions is maintained with the epithelial cells by sodium-potassium ATPase moving sodium ions into the blood – the second mechanism of active transport. The symporter then returns to the original position and as the concentration of glucose is higher in the cell than that in the blood, glucose diffuses down its gradient out of the cell, into the blood via facilitated diffusion using the GLuT1 uniporter (which only allow movement of a solute with its concentration gradient).
FIGURE OF THIS OVERALL MOVEMENT
An example of an antiporter is the sodium-calcium antiporter, important for stimulating contractions within cardiac muscle cells. Stronger contractions are triggered by high concentrations of intracellular calcium ions, so antiporters reduce the concentration to reduce the strength of the muscle contraction. Again, the electrochemical gradient set up by sodium ions moves sodium ions into the cell, along the concentration gradient. Once three sodium ions have bound to the antiporter, this displaces the one calcium ion already attached the binding site and by doing so, transports the calcium ion against its gradient to the outside of the cell by triggering a conformational change of the protein. The sodium ions are then displaced by another calcium ion from inside the cell as the binding site has a higher affinity for calcium, allowing the flow of sodium into the cell. This maintains the very low concentration of calcium within the cardiac muscle cells.
FIGURE OF THIS EXAMPLE
Exocytosis
Exocytosis is also known as secretion as it involves the movement of vesicles containg material to plasma membranes and the release of this cargo. There are two types of exocytosis, regulated and constitutive. Regulated exocytosis is the release of cargo from vesicles, triggered by a direct stimulus, whereas constitutive exocytosis is the continual process of release of contents from a vesicle. An example of regulated exocytosis is the release of histamine by mast cells when triggered by the binding of bradykinin to the mast cells. This allows more fluid and macrophages to move out of the capillaries to the site of invading organisms and pathogens to prevent infection.
References:
Hardin et al. (2012). Becker's world of the cell, global edition. 8th ed. [S.l.]: Pearson Education Limited., pp.156-219
Berg et al. (2011). Biochemistry. Basingstoke: W.H.Freeman & Co Ltd, pp.357-406.
Moran et al. (2013). Principles of biochemistry. 5th ed. Harlow: Pearson education limited, pp.307-349.
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