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Types of transport molecules | Vesicle-mediated transport | Learning Objectives | Terms | Links | References
Cell membranes act as barriers to most, but not all, molecules. Development of a cell membrane that could allow some materials to pass while constraining the movement of other molecules was a major step in the evolution of the cell. Cell membranes are differentially (or semi-) permeable barriers separating the inner cellular environment from the outer cellular (or external) environment.
Water potential is the tendency of water to move from an area of higher concentration to one of lower concentration. Energy exists in two forms: potential and kinetic. Water molecules move according to differences in potential energy between where they are and where they are going. Gravity and pressure are two enabling forces for this movement. These forces also operate in the hydrologic (water) cycle. Remember in the hydrologic cycle that water runs downhill (likewise it falls from the sky, to get into the sky it must be acted on by the sun and evaporated, thus needing energy input to power the cycle).
The hydrologic cycle. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Diffusion is the net movement of a substance (liquid or gas) from an area of higher concentration to one of lower concentration. You are on a large (10 ft x 10 ft x10 ft) elevator. An obnoxious individual with a lit cigar gets on at the third floor with the cigar still burning. You are also unfortunate enough to be in a very tall building and the person says "Hey we're both going to the 62nd floor!" Disliking smoke you move to the farthest corner you can. Eventually you are unable to escape the smoke! An example of diffusion in action. Nearer the source the concentration of a given substance increases. You probably experience this in class when someone arrives freshly doused in perfume or cologne, especially the cheap stuff.
Since the molecules of any substance (solid, liquid, or gas) are in motion when that substance is above absolute zero (0 degrees Kelvin or -273 degrees C), energy is available for movement of the molecules from a higher potential state to a lower potential state, just as in the case of the water discussed above. The majority of the molecules move from higher to lower concentration, although there will be some that move from low to high. The overall (or net) movement is thus from high to low concentration. Eventually, if no energy is input into the system the molecules will reach a state of equilibrium where they will be distributed equally throughout the system.
The cell membrane functions as a semi-permeable barrier, allowing a very few molecules across it while fencing the majority of organically produced chemicals inside the cell. Electron microscopic examinations of cell membranes have led to the development of the lipid bilayer model (also referred to as the fluid-mosaic model). The most common molecule in the model is the phospholipid, which has a polar (hydrophilic) head and two nonpolar (hydrophobic) tails. These phospholipids are aligned tail to tail so the nonpolar areas form a hydrophobic region between the hydrophilic heads on the inner and outer surfaces of the membrane. This layering is termed a bilayer since an electron microscopic technique known as freeze-fracturing is able to split the bilayer.
Diagram of a phospholipid bilayer. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Phospholipids and glycolipids are important structural components of cell membranes. Phospholipids are modified so that a phosphate group (PO4-) replaces one of the three fatty acids normally found on a lipid. The addition of this group makes a polar "head" and two nonpolar "tails".
Structure of a phospholipid, space-filling model (left) and chain model (right). Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Diagram of a cell membrane. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Cell Membranes from Opposing Neurons (TEM x436,740). This image is copyright Dennis Kunkel at www.DennisKunkel.com, used with permission.
Cholesterol is another important component of cell membranes embedded in the hydrophobic areas of the inner (tail-tail) region. Most bacterial cell membranes do not contain cholesterol.
Proteins are suspended in the inner layer, although the more hydrophilic areas of these proteins "stick out" into the cells interior as well as the outside of the cell. These integral proteins are sometimes known as gateway proteins. Proteins also function in cellular recognition, as binding sites for substances to be brought into the cell, through channels that will allow materials into the cell via a passive transport mechanism, and as gates that open and close to facilitate active transport of large molecules.
The outer surface of the membrane will tend to be rich in glycolipids, which have their hydrophobic tails embedded in the hydrophobic region of the membrane and their heads exposed outside the cell. These, along with carbohydrates attached to the integral proteins, are thought to function in the recognition of self. Multicellular organisms may have some mechanism to allow recognition of those cells that belong to the organism and those that are foreign. Many, but not all, animals have an immune system that serves this sentry function. When a cell does not display the chemical markers that say "Made in Mike", an immune system response may be triggered. This is the basis for immunity, allergies, and autoimmune diseases. Organ transplant recipients must have this response suppressed so the new organ will not be attacked by the immune system, which would cause rejection of the new organ. Allergies are in a sense an over reaction by the immune system. Autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythmatosis, happen when for an as yet unknown reason, the immune system begins to attack certain cells and tissues in the body.
Water, carbon dioxide, and oxygen are among the few simple molecules that can cross the cell membrane by diffusion (or a type of diffusion known as osmosis ). Diffusion is one principle method of movement of substances within cells, as well as the method for essential small molecules to cross the cell membrane. Gas exchange in gills and lungs operates by this process. Carbon dioxide is produced by all cells as a result of cellular metabolic processes. Since the source is inside the cell, the concentration gradient is constantly being replenished/re-elevated, thus the net flow of CO2 is out of the cell. Metabolic processes in animals and plants usually require oxygen, which is in lower concentration inside the cell, thus the net flow of oxygen is into the cell.
Osmosis is the diffusion of water across a semi-permeable (or differentially permeable or selectively permeable) membrane. The cell membrane, along with such things as dialysis tubing and cellulose acetate sausage casing, is such a membrane. The presence of a solute decreases the water potential of a substance. Thus there is more water per unit of volume in a glass of fresh-water than there is in an equivalent volume of sea-water. In a cell, which has so many organelles and other large molecules, the water flow is generally into the cell.
Animated image/movie illustrating osmosis (water is the red dots) and the selective permeability of a membrane (blue dashed line). Image from the Internet. Click on image to view movie.
Hypertonic solutions are those in which more solute (and hence lower water potential) is present. Hypotonic solutions are those with less solute (again read as higher water potential). Isotonic solutions have equal (iso-) concentrations of substances. Water potentials are thus equal, although there will still be equal amounts of water movement in and out of the cell, the net flow is zero.
Water relations and cell shape in blood cells. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Water relations in a plant cell. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
One of the major functions of blood in animals is the maintain an isotonic internal environment. This eliminates the problems associated with water loss or excess water gain in or out of cells. Again we return to homeostasis. Paramecium and other single-celled freshwater organisms have difficulty since they are usually hypertonic relative to their outside environment. Thus water will tend to flow across the cell membrane, swelling the cell and eventually bursting it. Not good for any cell! The contractile vacuole is the Paramecium's response to this problem. The pumping of water out of the cell by this method requires energy since the water is moving against the concentration gradient. Since ciliates (and many freshwater protozoans) are hypotonic, removal of water crossing the cell membrane by osmosis is a significant problem. One commonly employed mechanism is a contractile vacuole. Water is collected into the central ring of the vacuole and actively transported from the cell.
The functioning of a contractile vacuole in Paramecium. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Passive transport requires no energy from the cell. Examples include the diffusion of oxygen and carbon dioxide, osmosis of water, and facilitated diffusion.
Types of passive transport. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
Active transport requires the cell to spend energy, usually in the form of ATP. Examples include transport of large molecules (non-lipid soluble) and the sodium-potassium pump.
Types of active transport. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
The transport proteins integrated into the cell membrane are often highly selective about the chemicals they allow to cross. Some of these proteins can move materials across the membrane only when assisted by the concentration gradient, a type of carrier-assisted transport known as facilitated diffusion. Both diffusion and facilitated diffusion are driven by the potential energy differences of a concentration gradient. Glucose enters most cells by facilitated diffusion. There seem to be a limiting number of glucose-transporting proteins. The rapid breakdown of glucose in the cell (a process known as glycolysis) maintains the concentration gradient. When the external concentration of glucose increases, however, the glucose transport does not exceed a certain rate, suggesting the limitation on transport.
In the case of active transport, the proteins are having to move against the concentration gradient. For example the sodium-potassium pump in nerve cells. Na+ is maintained at low concentrations inside the cell and K+ is at higher concentrations. The reverse is the case on the outside of the cell. When a nerve message is propagated, the ions pass across the membrane, thus sending the message. After the message has passed, the ions must be actively transported back to their "starting positions" across the membrane. This is analogous to setting up 100 dominoes and then tipping over the first one. To reset them you must pick each one up, again at an energy cost. Up to one-third of the ATP used by a resting animal is used to reset the Na-K pump.
Uniport transports one solute at a time. Symport transports the solute and a cotransported solute at the same time in the same direction. Antiport transports the solute in (or out) and the co-transported solute the opposite direction. One goes in the other goes out or vice-versa.
Vesicles and vacuoles that fuse with the cell membrane may be utilized to release or transport chemicals out of the cell or to allow them to enter a cell. Exocytosis is the term applied when transport is out of the cell.
This GIF animation is from http://www.stanford.edu/group/Urchin/GIFS/exocyt.gif. Note the vesicle on the left, and how it fuses with the cell membrane on the right, expelling the vesicle's contents to the outside of the cell.
Endocytosis is the case when a molecule causes the cell membrane to bulge inward, forming a vesicle. Phagocytosis is the type of endocytosis where an entire cell is engulfed. Pinocytosis is when the external fluid is engulfed. Receptor-mediated endocytosis occurs when the material to be transported binds to certain specific molecules in the membrane. Examples include the transport of insulin and cholesterol into animal cells.
Endocytosis and exocytosis. Image from Purves et al., Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com), used with permission.
1. Relative concentrations
Molecules and ions move spontaneously down their concentration gradient (i.e., from a region of higher to a region of lower concentration) by diffusion.
Molecules and ions can be moved against their concentration gradient, but this process, called active transport, requires the expenditure of energy (usually from ATP).
2. Lipid bilayers are impermeable to most essential molecules and ions.
The lipid bilayer is permeable to water molecules and a few other small, uncharged, molecules likeThis page will examine how ions and small molecules are transported across cell membranes. The transport of macromolecules through membranes is described in Endocytosis.
Link to a quantitative treatment of the free energy changes involved in facilitated diffusion and active transport. |
Facilitated diffusion of ions takes place through proteins, or assemblies of proteins, embedded in the plasma membrane. These transmembrane proteins form a water-filled channel through which the ion can pass down its concentration gradient.
The transmembrane channels that permit facilitated diffusion can be opened or closed. They are said to be "gated".
Some types of gated ion channels:External ligands (shown here in green) bind to a site on the extracellular side of the channel.
Examples:
Internal ligands bind to a site on the channel protein exposed to the cytosol.
Examples:
Examples:
In so-called "excitable" cells like neurons and muscle cells, some channels open or close in response to changes in the charge (measured in volts) across the plasma membrane.
Example: As an impulse passes down a neuron, the reduction in the voltage opens sodium channels in the adjacent portion of the membrane. This allows the influx of Na+ into the neuron and thus the continuation of the nerve impulse. [More]
Some 7000 sodium ions pass through each channel during the brief period (about 1 millisecond) that it remains open. This was learned by use of the patch clamp technique.
Such measurements reveal that each channel is either fully open or fully closed; that is, facilitated diffusion through a single channel is "all-or-none".
This technique has provided so much valuable information about ion channels that its inventors, Erwin Neher and Bert Sakmann, were awarded a Nobel Prize in 1991.
Some small, hydrophilic organic molecules, like sugars, can pass through cell membranes by facilitated diffusion.
Once again, the process requires transmembrane proteins. In some cases, these — like ion channels — form water-filled pores that enable the molecule to pass in (or out) of the membrane following its concentration gradient.
Example: Maltoporin. This homotrimer in the outer membrane of E. coli forms pores that allow the disaccharide maltose and a few related molecules to diffuse into the cell.
Another example: The plasma membrane of human red blood cells contain transmembrane proteins that permit the diffusion of glucose from the blood into the cell.
Note that in all cases of facilitated diffusion through channels, the channels are selective; that is, the structure of the protein admits only certain types of molecules through.
Whether all cases of facilitated diffusion of small molecules use channels is yet to be proven. Perhaps some molecules are passed through the membrane by a conformational change in the shape of the transmembrane protein when it binds the molecule to be transported.
In either case, the interaction between the molecule being transported and its transporter resembles in many ways the interaction between an enzyme and its substrate. Link to a discussion of the energetics of enzyme-substrate interactions. |
Active transport is the pumping of molecules or ions through a membrane against their concentration gradient. It requires:
The energy of ATP may be used directly or indirectly.
Link to a quantitative analysis of these processes. |
The cytosol of animal cells contains a concentration of potassium ions (K+) as much as 20 times higher than that in the extracellular fluid. Conversely, the extracellular fluid contains a concentration of sodium ions (Na+) as much as 10 times greater than that within the cell.
These concentration gradients are established by the active transport of both ions. And, in fact, the same transporter, called the Na+/K+ ATPase, does both jobs. It uses the energy from the hydrolysis of ATP to
The crucial roles of the Na+/K+ ATPase are reflected in the fact that almost one-third of all the energy generated by the mitochondria in animal cells is used just to run this pump.
The parietal cells of your stomach use this pump to secrete gastric juice. These cells transport protons (H+) from a concentration of about 4 x 10-8 M within the cell to a concentration of about 0.15 M in the gastric juice (giving it a pH close to 1). Small wonder that parietal cells are stuffed with mitochondria and uses huge amounts of ATP as they carry out this three-million fold concentration of protons.
A Ca2+ ATPase is located in the plasma membrane of all eukaryotic cells. It uses the energy provided by one molecule of ATP to pump one Ca2+ ion out of the cell. The activity of these pumps helps to maintain the ~20,000-fold concentration gradient of Ca2+ between the cytosol (~ 100 nM) and the ECF (~ 20 mM). [More]
In resting skeletal muscle, there is a much higher concentration of calcium ions (Ca2+) in the sarcoplasmic reticulum than in the cytosol. Activation of the muscle fiber allows some of this Ca2+ to pass by facilitated diffusion into the cytosol where it triggers contraction. [Link to discussion].
After contraction, this Ca2+ is pumped back into the sarcoplasmic reticulum. This is done by another Ca2+ ATPase that uses the energy from each molecule of ATP to pump 2 Ca2+ ions.
Pumps 1. - 3. are designated P-type ion transporters because they use the same basic mechanism: a conformational change in the proteins as they are reversibly phosphorylated by ATP. And all three pumps can be made to run backward. That is, if the pumped ions are allowed to diffuse back through the membrane complex, ATP can be synthesized from ADP and inorganic phosphate.
The ligand-binding domain is usually restricted to a single type of molecule.
The ATP bound to its domain provides the energy to pump the ligand across the membrane.
The human genome contains 48 genes for ABC transporters. Some examples:
Indirect active transport uses the downhill flow of an ion to pump some other molecule or ion against its gradient. The driving ion is usually sodium (Na+) with its gradient established by the Na+/K+ ATPase.
In this type of indirect active transport, the driving ion (Na+) and the pumped molecule pass through the membrane pump in the same direction.
Examples:External Link |
Link to an animation of the process produced by the father and son team of John and John Giannini. |
Please let me know by e-mail if you find a broken link in my pages.) |
The Na+/glucose transporter is used to actively transport glucose out of the intestine and also out of the kidney tubules and back into the blood.
The energy relationships for these processes can be quantified. Link to a discussion. |
In antiport pumps, the driving ion (again, usually sodium) diffuses through the pump in one direction providing the energy for the active transport of some other molecule or ion in the opposite direction.
Example: Ca2+ ions are pumped out of cells by sodium-driven antiport pumps [Link].
Antiport pumps in the vacuole of some plants harness the outward facilitated diffusion of protons (themselves pumped into the vacuole by a H+ ATPase)A growing number of human diseases have been discovered to be caused by inherited mutations in genes encoding channels.
Some examples:Example: the reabsorption of water from the kidney tubules back into the blood depends on the water following behind the active transport of Na+. [Discussion]
If the concentration of water in the medium surrounding a cell is greater than that of the cytosol, the medium is said to be hypotonic. Water enters the cell by osmosis.
A red blood cell placed in a hypotonic solution (e.g., pure water) bursts immediately ("hemolysis") from the influx of water.
Plant cells and bacterial cells avoid bursting in hypotonic surroundings by their strong cell walls. These allow the buildup of turgor within the cell. When the turgor pressure equals the osmotic pressure, osmosis ceases.
How the kidneys of freshwater fishes and amphibians permit their owners to live in their hypotonic surroundings. |
When red blood cells are placed in a 0.9% salt solution, they neither gain nor lose water by osmosis. Such a solution is said to be isotonic.
The extracellular fluid (ECF) of mammalian cells is isotonic to their cytoplasm. This balance must be actively maintained because of the large number of organic molecules dissolved in the cytosol but not present in the ECF. These organic molecules exert an osmotic effect that, if not compensated for, would cause the cell to take in so much water that it would swell and might even burst. This fate is avoided by pumping sodium ions out of the cell with the Na+/K+ ATPase.
If red cells are placed in sea water (about 3% salt), they lose water by osmosis and the cells shrivel up. Sea water is hypertonic to their cytosol.
Similarly, if a plant tissue is placed in sea water, the cell contents shrink away from the rigid cell wall. This is called plasmolysis. [Link to a view of it.]
Sea water is also hypertonic to the ECF of most marine vertebrates. To avoid fatal dehydration, these animals (e.g., bony fishes like the cod) must
Marine birds, which may pass long periods of time away from fresh water, and sea turtles use a similar device. They, too, drink salt water to take care of their water needs and use metabolic energy to desalt it. In the herring gull, shown here, the salt is extracted by two glands in the head and released (in a very concentrated solution — it is saltier than the blood) to the outside through the nostrils. Marine snakes use a similar desalting mechanism.
How the kidneys of marine fishes are adapted for life in a hypertonic environment. |
Osmosis is important! A report in the 23 April 1998 issue of The New England Journal of Medicine tells of the life-threatening complications that can be caused by an ignorance of osmosis.
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Albert Szent-Györgyi | |
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Albert Szent-Györgyi at the time of his
appointment to the National Institutes of Health |
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Born | September 16, 1893 Budapest, Austria-Hungary |
Died | October 22, 1986 (aged 93) Woods Hole, Massachusetts, United States |
Residence | Austria-Hungary United States |
Citizenship | Austro-Hungarian United States |
Fields | Physiology Biochemistry |
Institutions | University of Szeged University of Cambridge |
Alma mater | Semmelweis University, MD University of Cambridge, PhD |
Doctoral advisor | Frederick Gowland Hopkins |
Known for | vitamin C, discovering the components and reactions of the citric acid cycle |
Influences | Hartog Jacob Hamburger Frederick Gowland Hopkins |
Notable awards | Nobel Prize in Physiology or Medicine in 1937 |
Spouse |
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Signature |
Albert Szent-Györgyi de Nagyrápolt (Hungarian: Nagyrápolti Szent-Györgyi Albert [ˈnɒɟraːpolti ˈsɛntˌɟørɟi ˈɒlbɛrt]; September 16, 1893 – October 22, 1986) was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937.[1] He is credited with discovering vitamin C and the components and reactions of the citric acid cycle. He was also active in the Hungarian Resistance during World War II and entered Hungarian politics after the war.