THE CELL MEMBRANE CONSISTS
OF A LIPID BILAYER WITH CELL
MEMBRANE TRANSPORT PROTEINS
- Lipid Bilayer
- Protein molecules embedded all the way in the membrane
- Barries between intra and extracellular fluid
- lipid-soluble substances can penetrate this lipid bilayer, diffusing directly through the lipid substance.
- Transport proteins transport various substances
- Water and ions transport through Channel protein
- Carrier proteins bind with ions and transport them across the cell membrane. conformational changes occur in the protein.
Diffusion
The continual movement of molecules among one another in
liquids or in gases is called diffusion.
Ions diffuse in the same manner as whole molecules,
and even suspended colloid particles diffuse in a similar
manner, except that the colloids diffuse far less rapidly
than do molecular substances because of their large size.
DIFFUSION THROUGH THE CELL MEMBRANE:
- two types of diffusion. simple diffusion and facilitated diffusion.
- In Simple diffusion no carrier protein required. In Fascilitated carrier, protein is required
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 and
(2) through watery channels that penetrate all the way
through some of the large transport proteins
Diffusion of Lipid-Soluble Substances Through the
Lipid Bilayer
- Lipid solubility
- lipid solubilities of oxygen, nitrogen, carbon dioxide, and alcohols are high, and all these substances can dissolve directly in the lipid bilayer and diffuse through the cell membrane
- The rate of diffusion is directly proportional to Lipid solubility
Diffusion of Water and Other Lipid-Insoluble Molecules Through Protein channels:
- Channel proteins, Aquaporins transport water through the lipid bilayer
- The aquaporins are highly specialized, and there are at least 13 different types in various cells of mammals.
- the total amount of water that diffuses in each direction through the red blood cell membrane during each second is about 100 times as great as the volume of the red blood cell itself.
DIFFUSION THROUGH PROTEIN PORES AND CHANNELS—SELECTIVE
PERMEABILITY AND “GATING” OF CHANNELS
Pores are composed of integral cell membrane proteins
that form open tubes through the membrane and are
always open. They are selective for each type of molecule.
The protein channels are distinguished by two important characteristics:
(1) They are often selectively permeable to certain substances, and
(2) many of the channels can be opened or closed by gates that are regulated by electrical signals (voltage-gated channels) or chemicals that bind to the channel proteins (ligand-gated channels.
Selective Permeability of Protein Channels
- protein channels are highly selective for the transport of one or more specific ions or molecules.
- This selectivity results from the characteristics of the channel, such as its diameter, shape, nature of the electrical charges, and chemical bonds along its inside surfaces.
- Potassium channels permit the passage of potassium ions across the cell membrane about 1000 times more readily than they permit the passage of sodium ions.
- Potassium channels have a tetrameric structure consisting of four identical protein subunits surrounding a central pore. At the top of the channel, the pore is pore loops that form a narrow selectivity filter.
- Lining the selectivity filter are carbonyl oxygens
- When hydrated potassium ions enter the selectivity filter, they interact with the carbonyl oxygens and shed most of their bound water molecules, permitting the dehydrated potassium ions to pass through the channel. The carbonyl oxygens are too far apart, however, to enable them to interact closely with the smaller sodium ions, which are therefore effectively excluded by the selectivity filter from passing through the pore.
- The sodium channel is only 0.3 to 0.5 nanometer in diameter, the inner surfaces of this channel are lined with amino acids that 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. then molecule move according to diffusion laws.
Gating of Protein Channels.
The opening and closing of gates are controlled in two
principal ways:
- Voltage gating. In the case of voltage gating, the
molecular conformation of the gate or of its chemical bonds responds to the electrical potential across the cell membrane.
a strong negative charge on the inside of the cell membrane could presumably 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 sodium to pass inward through the sodium pores. This process is the basic mechanism for eliciting action potentials in nerves that are responsible for nerve signals. In the bottom panel.
Potassium gates open when inside of cell become positive charged
Chemical (ligand) gating.
Some protein channel gates are opened by the binding of a chemical substance (a ligand) with the protein, which causes a conformational or chemical bonding change in the protein molecule that opens or closes the gate.
Effect of acetyl choline on acetyl choline channel is an example.
Acetylcholine opens the gate of this channel, providing a negatively charged pore about 0.65 nanometer in diameter that allows uncharged molecules or positive ions smaller than this diameter to pass through.
FACILITATED DIFFUSION REQUIRES
MEMBRANE CARRIER PROTEINS
Facilitated diffusion is also called carrier-mediated diffusion.
the rate of simple diffusion through an open channel increases proportionately with the concentration of the diffusing substance, in facilitated diffusion, the rate of diffusion approaches a
maximum, called Vmax, as the concentration of the diffusing substance increases. This is the difference between simple and facilitated diffusion. a carrier protein with a pore large enough to transport a specific molecule part way through. It also shows a binding “receptor” on the inside of the
protein carrier. The molecule to be transported enters the pore and becomes bound. Then, in a fraction of a second, a conformational or chemical change occurs in the carrier protein, so the pore now opens to the opposite side of the membrane. Because the binding force of the receptor is
weak, the thermal motion of the attached molecule causes it to break away and be released on the opposite side of the membrane. The rate at which molecules can be transported by this mechanism can never be greater than the rate at which the carrier protein molecule can undergo change back and forth between its two states.
Among the many substances that cross cell membranes by facilitated diffusion are glucose and most of the amino acids. In the case of glucose, at least 14 members of a family of membrane proteins (called GLUT) that transport glucose molecules have been discovered in various tissues. Some of these GLUT transport other monosaccharides that have structures similar to that of glucose, including galactose and fructose. One of these, glucose transporter 4 (GLUT4), is activated by insulin, which can increase the rate of facilitated diffusion of glucose as much as 10- to 20-fold in insulin-sensitive tissues. This is the principal mechanism by which insulin controls glucose use in the body.
FACTORS THAT AFFECT NET RATE
OF DIFFUSION:
The net rate of diffusion is determined by several factors.
Net Diffusion Rate Is Proportional to the Concentration Difference Across a Membrane
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 and Vice versa. the rate of net diffusion into the
cell is proportional to the concentration on the outside
minus the concentration on the inside
Net diffusion ∝ ( Co − C i )
in which Co is concentration outside and Ci is concentration inside.
Effect of Membrane Electrical Potential on Diffusion
of Ions—The “Nernst 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.
the concentration of negative ions is the same on both sides of the membrane, but a positive charge has been applied to the right side of the membrane and a negative charge has been applied to the left, creating
an electrical gradient across the membrane. The positive charge attracts the negative ions, whereas the negative charge repels them. Therefore, net diffusion occurs from left to right. After some time, large quantities of negative ions have moved to the right, creating the condition
shown in the right panel of Figure 4-9B, in which a concentration difference of the ions has developed in the direction opposite to the electrical potential difference. The concentration difference now tends to move the ions
to the left, while the electrical difference tends to move them to the right. When the concentration difference rises high enough, the two effects balance each other. At normal body temperature (37°C), the electrical difference that will balance a given concentration difference of univalent ions—such as Na+ ions—can be determined from
the following formula, called the Nernst equation:
in which EMF is the electromotive force (voltage) between
side 1 and side 2 of the membrane, C1 is the concentration on side 1, and C2 is the concentration on side 2. This equation is extremely important in understanding the transmission of nerve impulses.
Effect of a Pressure Difference Across the Membrane.
Pressure actually means the sum of all the forces of the different molecules striking a unit surface area at a given instant. Therefore, having a higher pressure on one side of a membrane than on the other side means that the sum of all the forces of the molecules striking the channels on that side of the membrane is greater than on the other side. In most instances, this situation is caused by greater numbers of molecules striking the membrane per second on one side than on the other side. The result is that increased amounts of energy are available to cause a net movement of molecules from the high-pressure side toward the low-pressure side.
OSMOSIS ACROSS SELECTIVELY
PERMEABLE MEMBRANES—“NET
DIFFUSION” OF WATER
Enough water ordinarily diffuses in each direction through the red blood cell membrane per second to equal about 100 times the volume of
the cell itself.
Zero net movement of water. A balanced maintain across cell membrane. The process of net movement of water caused by a concentration difference of water is called osmosis.
Osmotic Pressure:
The amount of pressure required to stop osmosis is called the osmotic
the pressure.
Importance of Number of Osmotic Particles (Molar
Concentration) in Determining Osmotic Pressure.
The osmotic pressure exerted by particles in a solution,
whether they are molecules or ions, is determined by the
number of particles per unit volume of fluid, not by the
mass of the particles. The reason for this is that each
particle in a solution, regardless of its mass, exerts, on
average, the same amount of pressure against the membrane. That is, large particles, which have greater mass (m) than do small particles, move at slower velocities (v). The small particles move at higher velocities in such a way that their average kinetic energies (k), determined by the
equation are the same for each small particle as for each large particle. Consequently, the factor that determines the osmotic pressure of a solution is the concentration of the solution in terms of the number of particles (which is the same as its molar concentration if it is a nondissociated molecule), not in terms of the mass of the solute.
“Osmolality”—The Osmole
To express the concentration of a solution in terms of the numbers of particles, the unit called the osmole is used in place of grams.
180 grams of glucose, which is 1 gram
the molecular weight of glucose is equal to 1 osmole of
glucose. If a solute dissociates into two ions, 1 gram molecular
weight of the solute will become 2 osmoles because the
number of osmotically active particles is now twice as
great as is the case for the nondissociated solute. 1 gram molecular weight of sodium chloride, 58.5 grams, is equal to 2 osmoles.
Thus, a solution that has 1 osmole of solute dissolved in
each kilogram of water is said to have an osmolality of 1
osmole per kilogram, and a solution that has 1/1000
osmole dissolved per kilogram has an osmolality of 1 milliosmole per kilogram. The normal osmolality of the extracellular and intracellular fluids is about 300 million moles per kilogram of water.
At normal body temperature, 37°C, a concentration of 1
osmole per liter will cause 19,300 mm Hg osmotic pressure in the solution. Likewise, 1 milliosmole per liter concentration is equivalent to 19.3 mm Hg osmotic pressure. Multiplying this value by the 300-milliosmolar concentration of the body fluids gives a total calculated osmotic
pressure of the body fluids of 5790 mm Hg. The measured value for this, however, averages only about 5500 mm Hg. The reason for this difference is that many of the ions in the body fluids, such as sodium and chloride
ions, are highly attracted to one another; consequently, they cannot move entirely unrestrained in the fluids and create their full osmotic pressure potential. Therefore, on average, the actual osmotic pressure of the body fluids is about 0.93 times the calculated value.
The Term “Osmolarity.” Osmolarity is the osmolar
concentration expressed as osmoles per liter of the solution
rather than osmoles per kilogram of water. Although,
strictly speaking, it is osmoles per kilogram of water
(osmolality) that determines osmotic pressure, for dilute
solutions such as those in the body, the quantitative differences between osmolarity and osmolality are less than 1 percent. Because it is far more practical to measure osmolarity than osmolality, measuring osmolarity is the usual practice in almost all physiological studies.
“ACTIVE TRANSPORT” OF
SUBSTANCES THROUGH MEMBRANES
Movement of molecules or ions against concentration gradient and require energy.
Active transport is divided into two types
according to the source of the energy used to facilitate
the transport: primary active transport and secondary
active transport.
PRIMARY ACTIVE TRANSPORT
Sodium-Potassium Pump Transports
Sodium Ions Out of Cells and Potassium
Ions Into Cells
Among the substances that are transported by primary
active transport is sodium, potassium, calcium, hydrogen, chloride, and a few other ions. Na+-K+pump is an example. The carrier protein is a complex of two separate globular proteins—a larger one called the α subunit, with a molecular weight of about 100,000, and a
smaller one called the β 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:
- It has three binding sites for sodium ions on the
a portion of the protein that protrudes to the inside
of the cell. - It has two binding sites for potassium ions on the
outside. - The inside portion of this protein near the sodium
binding sites have adenosine triphosphatase (ATPase)
activity. below is the explainantion
- 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.
- Activation of the ATPase function leads to cleavage of one molecule of ATP, splitting it into 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.
- The Na+ K+ ATPase pump can run in reverse. If the electrochemical gradients for Na+ and K+ are experimentally increased to the degree that the energy stored in their gradients is greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration gradients and the Na+ K+ pump will synthesize ATP from ADP and phosphate.
- The relative concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+, determine the direction of the enzyme reaction. For some cells, such as electrically active nerve cells, 60 to 70 percent of the cells’ energy requirement may be devoted to pumping Na+ out of the cell and K+ into the cell.
The Na+K+ Pump Is Important for Controlling Cell
Volume.
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. As each time 3 Na out and 2 K in the water also moves out and prevents from swelling and bursting. Since a large number of negative proteins and organic molecules attract Na and K inside as they can not escape out of the cell and causes the movement of water inside of cell continuously but Na K pump stabilizes this phenomenon.
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, with high concentration outside the cell and 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, called co-transport, is one form of secondary active transport.
For sodium to pull another substance along with it, a coupling mechanism is required, which 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 become bound, a conformational change occurs, and energy released by the action of 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 action is entirely by co-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 high on the outside and low inside, which provides energy for 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. At least five amino acid transport proteins have been identified, each of which is responsible for transporting one subset of amino acids with specific molecular characteristics.
Sodium Counter-Transport of Calcium
and Hydrogen Ions
Two especially important counter-transport mechanisms
(i.e., transport in a direction opposite to the primary ion)
are sodium-calcium counter-transport and sodium hydrogen counter-transport. sodium ions moving to the interior and calcium ions to the exterior; both are bound to the same transport protein in a
counter-transport mode. This mechanism is in addition
to the primary active transport of calcium that occurs in
some cells.
Sodium-hydrogen counter-transport occurs in several
tissues. An especially important example is in the proximal tubules of the kidneys, where sodium ions move from the lumen of the tubule to the interior of the tubular cell while hydrogen ions are counter-transported into the tubule lumen.
Reference: This material is taken for study purpose from the book mention below
John_E_Hall__Guyton_and_Hall_Textbook_of_Medical_Physiology