© 2002, G. Holzer, all rights reserved.

Plasma Membrane and Cellular Transport

Content : - Plasma membrane - LDL, HDL - Simple diffusion - Passive mediated diffusion - Active mediated diffusion - Proton Pump - Na/K-pump - Co-transport - Ion channels - Membrane potential

- Comments and Questions - Back to Course Syllabus

What should you know in this chapter
Composition and properties of the membrane bilayer (contains mostly phospholips, glycolipds, cholestrol, proteins). Arrangement and function of proteins in the membrane. Osmotic pressure controlled by water exchange : hypertonic, hypotonic, isotonic solution. LDL, HDL. Simple diffusion (diffusion rates, direction of diffusion, gradients). Understand passive mediated transport (example)and active mediated transport using ATP or a gradient as energy source. Know all aspects of the Na+/K+ Pump. Membrane potential, function of ion gates (channels) and the conduction of electrical signals along nerve fibers. Ion channel diseases.
Plasma Membrane

As mentioned previously the plasma membrane is composed of a bilayer . This bilayer behaves very much like a fluid, that means the lipids in this bilayer are in constant lateral motions. The phospholipids can laterally exchange their places, however they can not diffuse transversely as shown below

The lipid components which make up the bilayer consist mostly of phospholipids and to a smaller extend of glycolipids . The plasma membrane is assymetric with respect to the lipid distribution. Glycolipids are generally found in the outside layer, whereas phospholipids are predominantly in the inside layer (cytoplasmic side) but they also are components of the outside layer. Glycolipids and glycoproteins embedded in the plasma membrane act as cell identidy markers. Cholesterol is another important component of the animal plasma membrane. Sometimes the content is as high as one molecule cholesterol per one molecule phospholipid. Cholesterol partially immobilizes the fatty acid tails making the membrane less flexible and thus less permeable to smaller molecules.

The other important components of the plasma membrane are proteins. Proteins can be associated with the outside (peripheral) of the membrane or they extend throughout the entire membrane (transmembrane). Mant of the plasma proteins are not fixed into a certain posistion, but can freely move within the membrane. The protein content of differs in membranes of different origin:

			protein		lipid 
	plasma membrane	50%		50%
	neuron		18%		79%
	mitochondrion	80%		20%
	liver		70% to 50%      30% to 50% 

Proteins in the plasma membrane serve as transporter molecules, i.e. they can transport substances in and out of the cell. They also function as recognition sites for substances such as hormones, transmitting chemical signal to the cell. Some proteins on the periphery of the plasma membrane function as enzymes, catalyzing chemical reactions.

The transport of lipids in the body occurs via a lipoprotein complex. Think about why lipids such as cholesterol are not transported in their pure form. The low density lipoprotein (LDL) is the form in which cholesterol is transported in the blood and taken up by cells. The uptake is mediated by a specific cell receptor which recognized the apoprotein. Individuals with abnormally high cholesterol levels are shown to have a defective cell receptor. High density lipoprotein (HDL) contain initially no cholesterol, however, over time HDL accumulates cholesterol. HDL can attach to receptors on the liver and return the cholesterol, where it is metabolized. Thus, high LDL levels in blood can cause coronary artery and cardiovascular diseases. High HDL levels reduce the risk of such diseases.

Simple diffusion ( add. slides )
Molecules, dissolved in liquids are not immobile. Depending on the temperature and viscosity of the liquid and the size of the molecules, they will move in a random motion in the liquid. This process is called diffusion and the speed by which they move is called the diffusion rate.

It measures an area covered in a second. A Na+ ion for example has a diffusion rate of about 10-5 cm/sec at room temperature in water. Suppose you measure the diffusion rate of Na+ across a lipid bilayer such as the one shown above. Because of the polar, ionic nature of Na+ it should not cross the bilayer, remember such an environment is very hydrophobic. The measured diffusion rate is extremely low : 10-9 cm/sec. Thus, the amount of Na+ crossing the bilayer in a given time is very low.

The transport of substances across the cellular plasma membrane can proceed through several different processes. the simplest process is ordinary diffusion. The direction of simple diffusion is from the high concentration to the low concentration until there is equilibrium. Then, the number of molecules crossing the membrane into the left compartment is the same as the those crossing into the right compartment. Thus, there in no net flux across the membrane. The rate of diffusion is directly proportional to the concentration difference between the two compartments.
As we have seen above, simple diffusion is not efficient way for solutes to cross the membrane. Most metabolites and nutrients which flow in and out of the cell are polar molecules, e.g. glucose, thus their diffusion rates are low. However, gases such as oxygen and carbon dioxide can diffuse directly across the membrane, since they are non polar.
Passive mediated transport

Because of the slow diffusion rate of polar molecules across the plasma membrane, cells use transmembrane proteins which attach to substances on one side of the membrane and conduct them through the bilayer over to the other side. For example, glucose is transported from the epithelial cells of the small intestine into the blood via a transporter protein. The transporter enzyme has specific binding sites for glucose on the cytoplasmic side of the epithelial plasma membrane to which glucose can attach. Once attached, the glucose molecules affect a change in the conformation of the transporter, causing it to flip and expose the glucose molecules to the outside of the membrane. The process is specific, i.e. only glucose and no other compounds transported. It is driven by the concentration gradient, with glucose having a higher concentration on the cytoplasmic side.

Active mediated transport

In many instances a substance has to be transported against its on gradient across the membrane. That means the substance is transported from a low concentration to a high concentration, which requires energy.
Many reactions in the cell are driven by the high energy compound ATP . ATP can also provide the energy to drive the transport of a solute against its one gradient as for example in the case of a proton pump. For example animal cells contain certain membrane bound compartments called lysosomes, whose interior is acidic (pH=5). The low pH in the lysosomes is maintained by a proton pump. The transport proceeds in several steps:
1. Phosphorylation of the H+ transporter by ATP on the outside of the lysosomal membrane .
2.The transfer of a phosphate causes a conformational change in the structure of the transporter protein, opening up a site to which a proton can attach .
3. The attachment of H+ causes a second conformational change, which results in the flip-over of the site which holds the H+, exposing it now to the inside of the lysosomes .
4. In this open conformation the H+ has no affinity anymore to the site and it can diffuse out. After the H+ has left, the phosphate bonded to the transporter protein becomes susceptible to hydrolysis. It diffuses away and the transporter is back to its original state. Thus, the transport of 1 H+ required 1 ATP.
An other example of an energy driven transport is the acidification of the stomach. The protons, which cause this acidity are extruded from epithelial cells (which line the stomach) into the stomach. The proton concentration inside the epithelial cell is much lower than in the stomach, thus the process needs energy. In this case the energy does not come from ATP but from an existing K+ gradient

Another example of an active mediated transport is the transport of Na + out of the cell and the simultaneous import of K+ into the cell by a transporter called Na/K-Pump. The cell must have a very low Na + content in the cytoplasm, since Na + deactivates many enzymes . In addition Na + requires much water for its hydration, which would cause the cells to swell and consequently burst. K+ , however is often necessary for enzymatic activity, thus the cell likes to keep its concentration high inside. K+ requires also less water for hydration, thus there is no danger of swelling. Consequently in organisms the extracellular space is high in Na + and low in K+, thus the transport of both ions is against their one gradients, requiring energy. As in the previous case this energy is provided by ATP . The actual exchange is shown below in the figure taken from your textbook.

In addition to ATP the cell can use also an existing gradient as an energy source for an active transport, called a co-transport. As described previously the Na+ concentration on the outside of the cell is high. In the example below glucose can be co-transported with Na+ from the outside to the inside. The Na+ ions are transported from the external side, where their concentration is high into the cytoplasm, where their concentration is low. The energy for the glucose transport into the cell is provided by Na - gradient.

Ion channels
Because of their charge, ions cannot diffuse through the plasma membrane. The bulk movement of ions across the membrane is controlled by ion channels. They are very important in the regulation of the cell's electrical potential . The cytoplasm of metabolizing cell contains many compounds which have negatively charged -COO- groups. They are degradation products of glucose as we shall see later. The Na/K-pump exports three positively charged ions (Na+) and imports only two positively charge ions (K+). Thus the medium outside of the cell contains a high concentration of Na+ making the exterior of the membrane slightly positive. As a result there is a membrane potential, i.e. a voltage across the plasma membrane in the order of -100 mV.
The cell membrane contains Na+ and K+ ion gates or leak channels as they are called. They play an important role in the propagation of an electrical signal along nerve fibers. They act as gates, which can be stimulated by a change in membrane potential (voltage gated) are by the attachment of a signaling compound to the ion gate (ligand gated). The transport through ion gates is very fast, about 1 million ions per second. This is 1000 times faster than the transport of Na+ and K+ by the Na/K-pump. Ion channels are not coupled to an energy source, which means that the transport is always passive, in direction from the high concentration side to the low concentration. Ion channels are specific, allowing only ions of the same ion radius to pass.
(add. slides) Some diseases such as cystic fibrosis are based on a malfunction of ion channels