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Chapter 3. Cell Biology - Advanced

3.25 Cell Transport - Advanced

Describe the importance of cell transport.

What is cell transport?

It is the movement of substances across the cell membrane either into or out of the cell. Sometimes things just move
through the phospholipid bilayer. Other times, substances need the assistance of a protein, like a channel protein or
some other transmembrane protein, to cross the cell membrane.
Cell Transport

Cell transport refers to the movement of substances across the cell membrane. Probably the most important feature of
a cells phospholipid membranes is that they are selectively permeable. A membrane that is selectively permeable,
or semipermeable, has control over what molecules or ions can enter or leave the cell, as shown in Figure 3.33. This
feature allows a cell to control the transport of materials, as dictated by the cells function. The permeability of a
membrane is dependent on the organization and characteristics of the membrane lipids and proteins. In this way,
cell membranes help maintain a state of homeostasis within cells (and tissues, organs, and organ systems) so that an
organism can stay alive and healthy.
Transport Across Membranes

The molecular make-up of the phospholipid bilayer limits the types of molecules that can pass through it. For
example, hydrophobic (water-hating) molecules, such as carbon dioxide (CO2 ) and oxygen (O2 ), can easily pass
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FIGURE 3.33
A selectively permeable, or semipermeable, membrane allows certain molecules
through, but not others.

through the lipid bilayer, but ions such as calcium (Ca2+ ) and polar molecules such as water (H2 O) cannot. The
hydrophobic interior of the phospholipid bilayer does not allow ions or polar molecules through because they are
hydrophilic, or water loving. In addition, large molecules such as sugars and proteins are too big to pass through
the phospholipid bilayer. Transport proteins within the membrane allow these molecules to cross the membrane into
or out of the cell. This way, polar molecules avoid contact with the nonpolar interior of the membrane, and large
molecules are moved through large pores.
Every cell is contained within a membrane punctuated with transport proteins that act as channels or pumps to let in
or force out certain molecules. The purpose of the transport proteins is to protect the cells internal environment and
to keep its balance of salts, nutrients, and proteins within a range that keeps the cell and the organism alive.
There are four main ways that molecules can pass through a phospholipid membrane. The first way requires no
energy input by the cell and is called simple diffusion. This type of transport includes passive diffusion and osmosis.
No assistance by a transport is necessary in simple diffusion. Facilitated diffusion, does involve the assistance of
transport proteins. The third way, called active transport, requires that the cell uses energy to pull in or pump out
certain molecules and ions. Active transport involves proteins known as pumps. The fourth way is through vesicle
transport, in which large molecules are moved across the membrane in bubble-like sacks that are made from pieces
of the membrane. Vesicular transport includes exocytosis and endocytosis.

Homeostasis and Cell Transport

Homeostasis refers to the balance, or equilibrium, within the cell or a body. It is an organisms ability to keep a constant internal environment. Keeping a stable internal environment requires constant adjustments as conditions change
inside and outside the cell. The adjusting of systems within a cell is referred to as homeostatic regulation. Because
the internal and external environments of a cell are constantly changing, adjustments must be made continuously to
stay at or near the normal proportions of all internal substances. This involves continual adjustments in transport of
substances across the cell membrane. Homeostasis is a dynamic equilibrium rather than an unchanging state. The
cellular processes discussed in the cell transport (passive and active transport) concepts all play an important role in
homeostatic regulation.
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Vocabulary

concentration gradient: Difference in the concentrations of a molecule across two distinct areas, such as a
cell membrane.
diffusion: The movement of molecules from an area of high concentration of the molecules to an area with a
lower concentration.
endocytosis: The cellular process of capturing a material/substance from outside the cell by vesicle formation.
exocytosis: The cellular process of secreting materials by vesicle fusion.
homeostasis: The process of maintaining a stable environment inside a cell or an entire organism.
passive transport: Transport of small molecules or ions across the cell membrane without an input of energy
by the cell.
selectively permeable: The ability to allow only certain molecules to cross the plasma membrane; semipermeable.
semipermeable: The feature of a cell membrane that allows only select molecules (ions and organic molecules)
to enter and/or leave the cell; the ability to allow only certain molecules to cross the plasma membrane;
selectively permeable.
Summary

The cell membrane is selectively permeable, allowing only certain substances to pass through.
Cell transport may require assistance by a protein/pump.
Cell transport may require energy.
Some transport involves vesicles.

Review

1. What is meant by cell transport? Why is cell transport important?

2. List types of cell transport.
3. Explain how cell transport helps an organism maintain homeostasis.

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3.26 Diffusion - Advanced

Define diffusion.

What will eventually happen to these dyes?

They will all blend together. The dyes will move through the water until an even distribution, or equilibrium, is
achieved. The process of moving from areas of high amounts of a substance to areas of low amounts of the same
substance is called diffusion.
Diffusion

Passive transport is a way that small molecules or ions move across the cell membrane without input of energy by
the cell. The three main kinds of passive transport are diffusion (or simple diffusion), osmosis, and facilitated diffusion. Simple diffusion and osmosis do not involve transport proteins. Facilitated diffusion requires the assistance of
proteins.
Diffusion is the movement of molecules from an area of high concentration of the molecules to an area with a lower
concentration. For cell transport, diffusion is the movement of small molecules across the cell membrane. The
difference in the concentrations of the molecules in the two areas is called the concentration gradient. The kinetic
energy of the molecules results in random motion, causing diffusion. In simple diffusion, this process proceeds
without the aid of a transport protein. it is the random motion of the molecules that causes them to move from an
area of high concentration to an area with a lower concentration.
Diffusion will continue until the concentration gradient has been eliminated. Since diffusion moves materials from
an area of higher concentration to the lower, it is described as moving solutes "down the concentration gradient."
The end result of diffusion is an equal concentration, or equilibrium, of molecules on both sides of the membrane.
At equilibrium, movement of molecules does not stop. At equilibrium, there is equal movement of materials in both
directions.
If a molecule can pass freely through a cell membrane, it will cross the membrane by diffusion ( Figure 3.34).
The inside of the plasma membrane is hydrophobic, so certain molecules cannot easily pass through the membrane.
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Recall the semipermeable nature of the lipid bilayer. Molecules that cannot easily pass through the bilayer include
ions and small hydrophilic molecules, such as glucose, and macromolecules, including proteins and RNA. Examples
of molecules that can easily diffuse across the plasma membrane include carbon dioxide and oxygen gas. These
molecules diffuse freely in and out of the cell, along their concentration gradient. Though water is a polar molecule,
it can also diffuse through the plasma membrane. The diffusion of water through the cell membrane is of such
importance to the cell that it is given a special name, osmosis.

FIGURE 3.34
Molecules move from an area of high
concentration to an area of lower concentration until an equilibrium is met. The
molecules continue to cross the membrane at equilibrium, but at equal rates in
both directions.

Vocabulary

concentration gradient: Difference in the concentrations of a molecule across two distinct areas, such as a
cell membrane.
diffusion: The movement of molecules from an area of high concentration of the molecules to an area with a
lower concentration.
equilibrium: State of equal concentration of a molecule, such as on both sides of the cell membrane.
passive transport: Transport of small molecules or ions across the cell membrane without an input of energy
by the cell.
Summary

The cell membrane is selectively permeable, allowing only certain substances to pass through.
Passive transport is a way that small molecules or ions move across the cell membrane without input of energy
by the cell. The three main kinds of passive transport are diffusion, osmosis, and facilitated diffusion.
Diffusion is the movement of molecules from an area of high concentration of the molecules to an area with a
lower concentration.
Review

1. What is diffusion? What is the main difference between simple diffusion and facilitated diffusion?
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2. What is a concentration gradient?
3. What happens at equilibrium?

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Chapter 3. Cell Biology - Advanced

3.27 Osmosis - Advanced

Define osmosis.
Distinguish between diffusion and osmosis.

Saltwater Fish vs. Freshwater Fish?

Fish cells, like all cells, have semi-permeable membranes. Eventually, the concentration of "stuff" on either side of
them will even out. A fish that lives in salt water will have somewhat salty water inside itself. Put it in the freshwater,
and the freshwater will, through osmosis, enter the fish, causing its cells to swell, and the fish will die. What will
happen to a freshwater fish in the ocean?
Osmosis

Imagine you have a cup that has 100ml water, and you add 15g of table sugar (sucrose, C12 H22 O11 ) to the water.
The sugar dissolves and the mixture that is now in the cup is made up of a solute (the sugar), that is dissolved in the
solvent (the water). The mixture of a solute in a solvent is called a solution.
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Imagine now that you have a second cup with 100ml of water, and you add 45 grams of sucrose to the water. Just
like the first cup, the sugar is the solute, and the water is the solvent. But now you have two mixtures of different
solute concentrations. In comparing two solutions of unequal solute concentration, the solution with the higher
solute concentration is hypertonic, and the solution with the lower concentration is hypotonic. Solutions of equal
solute concentration are isotonic. The first sugar solution is hypotonic to the second solution. The second sugar
solution is hypertonic to the first.
You now add the two solutions to a beaker that has been divided by a selectively permeable membrane. The pores
in the membrane are too small for the sugar molecules to pass through, but are big enough for the water molecules
to pass through. The hypertonic solution is on one side of the membrane and the hypotonic solution on the other.
The hypertonic solution has a lower water concentration than the hypotonic solution, so a concentration gradient of
water now exists across the membrane. Water molecules will move from the side of higher water concentration to
the side of lower concentration until both solutions are isotonic.

What if the two solutions being compared are on either side of a cell membrane? A hypertonic solution is one having
a larger concentration of a substance on the outside of a cell than is found within the cells themselves. A hypotonic
solution contains a lesser concentration of impermeable solutes outside the cell compared to within the cell.
Osmosis is the diffusion of water molecules across a selectively permeable membrane from an area of higher
concentration to an area of lower concentration. Water moves into and out of cells by osmosis. If a cell is in a
hypertonic solution, the solution has a lower water concentration than the cell cytosol does, and water moves out
of the cell until both solutions are isotonic. Cells placed in a hypotonic solution will take in water across their
membrane until both the external solution and the cytosol are isotonic.
A cell that does not have a rigid cell wall (such as a red blood cell), will swell and lyse (burst) when placed in a
hypotonic solution. Cells with a cell wall will swell when placed in a hypotonic solution, but once the cell is turgid
(firm), the tough cell wall prevents any more water from entering the cell. When placed in a hypertonic solution, a
cell without a cell wall will lose water to the environment, shrivel, and probably die. In a hypertonic solution, a cell
with a cell wall will lose water too. The plasma membrane pulls away from the cell wall as it shrivels, a process
called plasmolysis. Animal cells tend to do best in an isotonic environment, plant cells tend to do best in a hypotonic
environment. This is demonstrated in Figure 3.35.
Osmotic Pressure

When water moves into a cell by osmosis, osmotic pressure may build up inside the cell. If a cell has a cell wall, the
wall helps maintain the cells water balance. Osmotic pressure is the main cause of support in many plants. When a
plant cell is in a hypotonic environment, the osmotic entry of water raises the turgor pressure exerted against the cell
wall until the pressure prevents more water from coming into the cell. At this point the plant cell is turgid ( Figure
3.36). The effects of osmotic pressures on plant cells are shown in Figure 3.35.
Osmosis can be seen very effectively when potato slices are added to a high concentration of salt solution (hypertonic). The water from inside the potato moves out of the potato cells to the salt solution, which causes the potato
cells to lose turgor pressure. The more concentrated the salt solution, the greater the difference in the size and weight
of the potato slice after plasmolysis.
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FIGURE 3.35
Unless an animal cell (such as the red
blood cell in the top panel) has an adaptation that allows it to alter the osmotic
uptake of water, it will lose too much water
and shrivel up in a hypertonic environment. If placed in a hypotonic solution,
water molecules will enter the cell causing
it to swell and burst. Plant cells (bottom
panel) become plasmolyzed in a hypertonic solution, but tend to do best in a
hypotonic environment. Water is stored in
the central vacuole of the plant cell.

FIGURE 3.36
The central vacuoles of the plant cells in
this image are full of water, so the cells
are turgid.

The action of osmosis can be very harmful to organisms, especially ones without cell walls. For example, if a
saltwater fish (whose cells are isotonic with seawater), is placed in fresh water, its cells will take on excess water,
lyse, and the fish will die. Another example of a harmful osmotic effect is the use of table salt to kill slugs and snails.
Diffusion and osmosis are discussed at http://www.youtube.com/watch?v=aubZU0iWtgI (18:59).

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Controlling Osmosis

Organisms that live in a hypotonic environment such as freshwater, need a way to prevent their cells from taking
in too much water by osmosis. A contractile vacuole is a type of vacuole that removes excess water from a
cell. Freshwater protists, such as the paramecia shown in Figure 3.37, have a contractile vacuole. The vacuole is
surrounded by several canals, which absorb water by osmosis from the cytoplasm. After the canals fill with water,
the water is pumped into the vacuole. When the vacuole is full, it pushes the water out of the cell through a pore.
Other protists, such as members of the genus Amoeba, have contractile vacuoles that move to the surface of the cell
when full and release the water into the environment.

FIGURE 3.37
The contractile vacuole is the star-like
structure within the paramecia.

Vocabulary

contractile vacuole: An organelle found in freshwater protists involved in osmoregulation; pumps excess
water out of a cell.
hypotonic: In comparing two solutions of unequal solute concentration, the solution with the higher solute
concentration.
hypertonic: In comparing two solutions of unequal solute concentration, the solution with the lower solute
concentration.
isotonic: Solutions of equal solute concentration.
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osmosis: The diffusion of water molecules across a selectively permeable membrane.

osmotic pressure: Pressure exerted on a cell wall due to osmosis of water into a cell.
plasmolysis: The process where the cytoplasm pulls away from the cell wall due to the loss of water through
osmosis; occurs in plant cells.
solute: The substance that is dissolved in a solvent.
solution: Mixture that has the same composition throughout; mixture of a solute in a solvent.
solvent: A substance that dissolves another substance to form a solution.
Summary

Osmosis is the diffusion of water molecules across a semipermeable membrane and down a concentration
gradient. They can move into or out of a cell, depending on the concentration of the solute.
Review

1. How does osmosis differ from diffusion?

2. What would cause the central vacuole of a plant cell to shrunk and become smaller than normal? What is the
likely solute concentration of the cells environment which has caused this change?

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3.28 Facilitated Diffusion - Advanced

Describe facilitated transport mechanisms.
Define ion channels.
Identify the role of ion channels in facilitated diffusion.

Can you help me move?

What is one of the questions no one likes to be asked? Sometimes the cell needs help moving things as well, or
facilitating the diffusion process. And this would be the job of a special type of protein.
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Facilitated Diffusion

Facilitated diffusion is the diffusion of solutes through integral membrane transport proteins. Facilitated diffusion
is a type of passive transport. Even though facilitated diffusion involves transport proteins (and is essentially a
transport process), it can still be considered passive transport because the solute is moving down the concentration
gradient, and no input of energy is required. Facilitated diffusion utilizes proteins known as uniporters. A uniporter
can be either a channel protein or a carrier protein.
As was mentioned earlier, small nonpolar molecules can easily diffuse across the cell membrane. However, due to
the hydrophobic nature of the phospholipids that make up cell membranes, polar molecules and ions cannot do so.
Instead, they diffuse across the membrane through transport proteins. A transport protein completely spans the
membrane, and allows certain molecules or ions to diffuse across the membrane. Channel proteins, gated channel
proteins, and carrier proteins are three types of transport proteins that are involved in facilitated diffusion.
A channel protein, a type of transport protein, acts like a pore in the membrane that lets water molecules or small
ions through quickly. Water channel proteins allow water to diffuse across the membrane at a very fast rate. Ion
channel proteins allow ions to diffuse across the membrane.
A gated channel protein is a transport protein that opens a "gate," allowing a molecule to pass through the
membrane. Gated channels have a binding site that is specific for a given molecule or ion. A stimulus causes
the "gate" to open or shut. The stimulus may be chemical or electrical signals, temperature, or mechanical force,
depending on the type of gated channel. For example, the sodium gated channels of a nerve cell are stimulated by
a chemical signal which causes them to open and allow sodium ions into the cell. Glucose molecules are too big to
diffuse through the plasma membrane easily, so they are moved across the membrane through gated channels. In
this way glucose diffuses very quickly across a cell membrane, which is important because many cells depend on
glucose for energy.
A carrier protein is a transport protein that is specific for an ion, molecule, or group of substances. Carrier proteins
"carry" the ion or molecule across the membrane by changing shape after the binding of the ion or molecule. Carrier
proteins are involved in passive and active transport. A model of a channel protein and carrier proteins is shown in
Figure 3.38.
FIGURE 3.38
Facilitated diffusion through the cell membrane. Channel proteins and carrier proteins are shown (but not a gated-channel
protein). Water molecules and ions move
through channel proteins. Other ions or
molecules are also carried across the cell
membrane by carrier proteins. The ion or
molecule binds to the active site of a carrier protein. The carrier protein changes
shape, and releases the ion or molecule
on the other side of the membrane. The
carrier protein then returns to its original
shape.

An animation depicting facilitated diffusion can be viewed at http://www.youtube.com/watch?v=OV4PgZDRTQw

(1:36).

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Ion Channels

Ions such as sodium (Na+ ), potassium (K+ ), calcium (Ca2+ ), and chloride (Cl ), are important for many cell
functions. Because they are polar, these ions do not diffuse through the membrane. Instead they move through
ion channel proteins where they are protected from the hydrophobic interior of the membrane. Ion channels allow
the formation of a concentration gradient between the extracellular fluid and the cytosol. Ion channels are very
specific as they allow only certain ions through the cell membrane. Some ion channels are always open, others are
"gated" and can be opened or closed. Gated ion channels can open or close in response to different types of stimuli
such as electrical or chemical signals.
Vocabulary

carrier protein: A transport protein that is specific for an ion, molecule, or group of substances; carries the
ion or molecule across the membrane by changing shape after the binding of the ion or molecule.
channel protein: A transport protein that acts like a pore in the membrane that lets water molecules or small
ions through quickly.
facilitated diffusion: The diffusion of solutes through transport proteins in the plasma membrane.
gated channel protein: A transport protein that opens a "gate," allowing a molecule to flow through the
membrane.
ion channel: A channel protein that transports ions across the membrane by facilitated diffusion.
passive transport: Transport of small molecules or ions across the cell membrane without an input of energy
by the cell.
transport protein: A protein that completely spans the membrane, and allows certain molecules or ions to
diffuse across the membrane; channel proteins, gated channel proteins, and carrier proteins are three types of
transport proteins that are involved in facilitated diffusion.
uniporter: An integral membrane protein that is involved in facilitated diffusion; can be either a channel or a
carrier protein.
Summary

Facilitated diffusion is the diffusion of solutes through transport proteins in the plasma membrane. Channel
proteins, gated channel proteins, and carrier proteins are three types of transport proteins that are involved in
facilitated diffusion.
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Membrane Channels at http://phet.colorado.edu/en/simulation/membrane-channels .

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Review

1. Compare and contrast simple diffusion and facilitated diffusion. For each type of diffusion, give an example
of a molecule that is transported.
2. Explain the three types of transport proteins involved in facilitated diffusion.

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3.29 Active Transport - Advanced

Compare passive and active transport.
Explain how different types of active transport occur.

Need to move something really heavy?

If you did, it would take a lot of energy. Sometimes, moving things into or out of the cell also takes energy. How
would the cell move something against a concentration gradient? It starts by using energy.

Active Transport

In contrast to facilitated diffusion which does not require energy and carries molecules or ions down a concentration
gradient, active transport pumps molecules and ions against a concentration gradient. Sometimes an organism needs
to transport something against a concentration gradient, such as specific ions, or glucose and amino acids. The
only way this can be done is through active transport which uses transport proteins and energy that is produced by
cellular respiration (ATP) or through an electrochemical gradient. In active transport, the particles move across
a cell membrane from a lower concentration to a higher concentration. Active transport is the energy-requiring
process of pumping molecules and ions across membranes "uphill" against a gradient. The active transport of
small molecules or ions across a cell membrane is generally carried out by transport proteins that are found in the
membrane. These transport proteins have receptor regions that bind to specific molecules and transport them into
the cell. Larger molecules such as starch can also be actively transported across the cell membrane by vesicular
transport processes.
During active transport, specialized integral membrane proteins recognize the substance and allows it access. Essentially this process is forcing a ion or molecule to cross the membrane when normally it would not. Moving a
substance against its concentration gradient is known as primary active transport, and the proteins involved in it
as "pumps". This process uses the energy of ATP. In secondary active transport, energy from an electrochemical
gradient is used to transport substances. This process involves pore-forming proteins that form channels through the
cell membrane.
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Primary Active Transport

Primary active transport involves an integral membrane protein and the energy from ATP to transport molecules
across a membrane. This type of transport is mainly done by ATPases. ATPases are a class of enzymes that catalyze
the dephosphorylation of adenosine triphosphate into adenosine diphosphate (ADP) and a free phosphate ion. This
reaction releases energy, which is used to drive other chemical reactions that would not otherwise occur.
One ATPase necessary to all life is the sodium-potassium pump, which helps to maintain the cell potential. This
pump will be discussed in the Active Transport: The Sodium-Potassium Pump (Advanced) concept. Other sources of
energy for primary active transport are redox energy and photon energy (light energy). Redox energy is used in the
mitochondrial electron transport chain during cellular respiration. In this transport, the reduction energy of NADH
is used to move protons across the inner mitochondrial membrane against their concentration gradient. An example
of primary active transport using photon energy occurs during photosynthesis. During photosynthesis, proteins use
the energy of photons to create a proton gradient across the chloroplast thylakoid membrane. That energy is used to
pump H+ ions into the thylakoid.
Secondary Active Transport

In secondary active transport, which is also known as cotransport, energy is used to transport molecules across
a membrane. However, in contrast to primary active transport, there is no direct coupling of ATP. Instead, the
electrochemical potential difference created by pumping ions out of the cell is used. The process is called cotransport
because one carrier protein mediates the transport of both substances. The two main forms of this are antiport and
symport.
Antiport and Symport

The difference between the two types of cotransport depends on the direction of transport of the molecules. A system
in which one substance moves in one direction while cotransporting another substance in the other direction is called
antiport. Symport is transport of two substrates in the same direction across the membrane. The protein involved
in this transport is a symporter. The protein involved in antiport is an antiporter.
The energy for these processes come from an electrochemical gradient. In such a gradient, one of the two substances
is transported in the direction of their concentration gradient,and the energy derived is used to transport the second
substance against its concentration gradient. Thus, energy stored in the electrochemical gradient of an ion is
used to drive the transport of another solute against a concentration or electrochemical gradient. In antiport,
one substance moves along its electrochemical gradient, allowing a different substance to move against its own
electrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are moved
against their concentration gradients, fueled by ATP. In symport, one substance moves down the electrochemical
gradient, allowing the other molecule(s) to move against its concentration gradient. One substance moves by
facilitated diffusion, which is coupled with the active transport of the other substance.
Vocabulary

active transport: Transport of molecules and ions across membranes against a concentration gradient; requires energy.
antiport: The secondary active transport process of transporting two or more different molecules or ions
across a phospholipid membrane in opposite directions.
antiporter: An integral membrane protein involved in secondary active transport; transports two or more
different molecules or ions across a phospholipid membrane in opposite directions.
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ATPase: A class of enzymes that catalyze the decomposition of adenosine triphosphate (ATP) into adenosine
diphosphate (ADP) and a free phosphate ion.
cotransport: The simultaneous or sequential transport of more than one molecule or ion across biological
membranes; also known as secondary active transport.
electrochemical gradient: Difference across a membrane due to both a chemical force and an electrical force;
drives the movement of ions across the membrane.
primary active transport: Active transport in which solutes are moved against their concentration gradients;
fueled by ATP.
redox energy: Energy that is either stored or released by redox reactions.
secondary active transport: Active transport in which one substance moves along its electrochemical gradient, allowing a different substance to move against its own electrochemical gradient; also known as cotransport.
symport: The secondary active transport process of transporting two or more different molecules or ions
across a phospholipid membrane in the same direction.
symporter: An integral membrane protein involved in secondary active transport; transports two or more
different molecules or ions across a phospholipid membrane in the same direction.
Summary

Active transport moves molecules across a cell membrane from an area of lower concentration to an area of
higher concentration. Active transport requires the use of energy.
The active transport of small molecules or ions across a cell membrane is generally carried out by transport
proteins that are found in the membrane.
During antiport and symport two substances are cotransported.
Explore More

Diffusion, Osmosis and Active Transport at http://www.concord.org/activities/diffusion-osmosis-and-acti

ve-transport .
Active Transport

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Review

1. What is active transport?

2. Describe the main difference between primary and secondary active transport.
3. Explain antiport and symport.

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3.30 The Sodium-Potassium Pump - Advanced

Explain how different types of active transport occur.
Describe the function of the sodium-potassium pump.

What is this incredible object?

Would it surprise you to learn that it is a human cell? The image represents an active human nerve cell. How nerve
cells function will be the focus of another concept. However, active transport processes play a significant role in the
function of these cells. Specifically, it is the sodium-potassium pump that is active in the axons of these nerve cells.
The Sodium-Potassium Pump

Carrier proteins can work with a concentration gradient (passive transport), but some carrier proteins can move
solutes against the concentration gradient (from low concentration to high concentration), with energy input from
ATP. As in other types of cellular activities, ATP supplies the energy for most active transport. One way ATP powers
active transport is by transferring a phosphate group directly to a carrier protein. This may cause the carrier protein
to change its conformation, which moves the molecule or ion to the other side of the membrane. An example of
this type of active transport system, as shown in Figure 3.39, is the sodium-potassium pump, or Na+ /K+ -ATPase,
a transmembrane ATPase, an integral membrane protein that exchanges sodium ions for potassium ions across the
plasma membrane of animal cells. The sodium-potassium pump is found in the plasma membrane of almost every
human cell and is common to all cellular life. It helps maintain resting potential, especially in neurons following a
nerve impulse, and regulates cellular volume.
The Mechanism

As is shown in Figure 3.39, the sodium-potassium pump transports Na+ ions and K+ ions in the following manner:
1. The sodium-potassium pump binds ATP and three intracellular Na+ ions.
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FIGURE 3.39
The sodium-potassium pump system
moves

sodium

and

potassium

ions

against large concentration gradients. It

moves two potassium ions into the cell
where potassium levels are high, and
pumps three sodium ions out of the cell
and into the extracellular fluid.

2. ATP is hydrolyzed resulting in adenosine diphosphate (ADP) and an inorganic phosphate. The free phosphate
phosphorylates the sodium-potassium pump.
3. A conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of the
pump has a low affinity for Na+ ions, so they are released.
4. The pump binds two extracellular K+ ions. This causes the dephosphorylation of the pump, reverting it to its
previous conformational state, transporting the K+ ions into the cell.
5. The unphosphorylated form of the pump has a higher affinity for Na+ ions than K+ ions, so the two bound
K+ ions are released.
6. ATP binds, and the process starts again.
A more detailed look at the sodium-potassium pump is available at http://www.youtube.com/watch?v=C_H-ONQFj
pQ (13:53) and http://www.youtube.com/watch?v=ye3rTjLCvAU (6:48).

MEDIA
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URL: http://www.ck12.org/flx/render/embeddedobject/208

MEDIA
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URL: http://www.ck12.org/flx/render/embeddedobject/500

Vocabulary

Na+ /K+ -ATPase: An active transport carrier protein/a transmembrane ATPase; moves sodium and potassium
ions against large concentration gradients; the sodium-potassium pump.
resting potential: The membrane potential of a cell/neuron at rest; the membrane potential of an unstimulated
neuron.
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sodium-potassium pump: An active transport carrier protein/a transmembrane ATPase; moves sodium and
potassium ions against large concentration gradients; the Na+ /K+ -ATPase.
Summary

The sodium-potassium pump is an example of an active transport membrane protein/transmembrane ATPase.

Using the energy from ATP, the sodium-potassium moves three sodium ions out of the cell and brings two
potassium ions into the cell.
Explore More

Use this resource to answer the questions that follow.

The Sodium Potassium Pump at http://hyperphysics.phy-astr.gsu.edu/hbase/biology/nakpump.html .
1.
2.
3.
4.
5.

Are there more sodium ions on the outside of cells or the inside?
Are there more potassium ions on the outside of cells or the inside?
What is the hydrolysis of ATP?
In what type of cells can a sodium-potassium pump be found?
What is the role of the sodium-potassium pump?

Review

1. What is the sodium-potassium pump?

2. Why is the pump called a transmembrane ATPase?
3. Outline how the sodium-potassium pump works.

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Chapter 3. Cell Biology - Advanced

3.31 The Electrochemical Gradient - Advanced

Describe the electrochemical gradient.

Do you really have electricity flowing through your body?

Yes you do. These electrical signals allow information to flow through the nervous system extremely rapidly. And it
all starts with the formation of an electrochemical gradient.
The Electrochemical Gradient

The active transport of ions across the cell membrane causes an electrical gradient to build up across this membrane.
The number of positively charged ions outside the cell is usually greater than the number of positively charged ions
in the cytosol. This results in a relatively negative charge on the inside of the membrane, and a positive charge on
the outside. This difference in charges causes a voltage to exist across the membrane. Voltage is electrical potential
energy that is caused by a separation of opposite charges, in this case across the membrane. The voltage across
a membrane is the membrane potential. Membrane potential is very important for the conduction of electrical
impulses along nerve cells. The membrane potential of a cell at rest is known as its resting potential, and is
discussed below. A non-excited nerve cell is an example of a cell at rest.
Because of the ion gradient, there are less positive ions inside the cell, the inside of the cell is negative compared
to outside the cell. This resulting membrane potential favors the movement of positively charged ions (cations) into
the cell, and the movement of negative ions (anions) out of the cell. So, there are two forces that drive the diffusion
of ions across the plasma membranea chemical force (the ions concentration gradient), and an electrical force
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(the effect of the membrane potential on the ions movement). These two forces working together are called an
electrochemical gradient.
The electrochemical gradient determines the direction an ion moves by diffusion or active transport across a membrane. In mitochondria and chloroplasts, proton gradients are used to generate a chemiosmotic potential that is
also known as a proton motive force, due to both the proton gradient and voltage gradient across the membrane.
This potential energy is used for the synthesis of ATP by oxidative phosphorylation.

The Resting Potential

In order to maintain the membrane potential, cells maintain a low concentration of sodium ions (Na+ ) and high
levels of potassium ions (K+ ) within the cell (intracellular). The sodium-potassium pump moves three Na+ ions out
of the cell and brings two K+ ions into the cell. This essentially removes one positive charge from the intracellular
space. The resulting membrane potential is known as the resting potential.

FIGURE 3.40
This diagram shows how ions maintain the membrane potential.

The

sodium-potassium pump is shown in the

membrane, transporting three Na+ ions
(green) out of the cell and bringing two K+
ions (blue) into the cell.

The Ion Gradient

The electrochemical potential across a membrane determines the tendency of an ion to cross the membrane. The
membrane may be that of a cell or organelle or other sub cellular compartment. The electrochemical potential arises
from three factors:
1. the difference in the concentration of the ions on either side of the membrane,
2. the charge of the ions (for example Na+ , Ca++ , Cl ), and
3. the difference in voltage between the two sides of the membrane (the transmembrane potential).
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Cotransport of ions by symporters and antiporter carriers is commonly used to actively move ions across biological
membranes. Transmembrane ATPases are often involved in maintaining ion gradients. The Na+/K+ ATPase uses
ATP to build and maintain a sodium ion gradient and a potassium ion gradient.

Proton Gradients and ATP synthase

One particular ion gradient with biological significance is the proton (H+ ) gradient. This type of gradient is
established through active transport involving proton pumps. The proton gradient is used during photosynthesis
and cellular respiration to generate a chemiosmotic potential, or proton motive force. This potential energy is used
for the synthesis of ATP by oxidative phosphorylation. The proton gradient can also be used to store energy for heat
production and flagellar rotation.
The energy held within the proton gradient can be used to synthesize ATP. ATP synthase is a transmembrane enzyme
that provides energy for the cell to use by producing ATP. The protein has two distinct regions, F0 and F1 . The F0
domain is embedded within the membrane, while the F1 domain is above the membrane, inside the matrix of the
mitochondria, or the stroma of the chloroplast. The F0 region is the proton pore, allowing hydrogen ions to diffuse
across the membrane. The F1 region of the protein has ATP synthesis activity, catalyzing the formation of ATP from
ADP and inorganic phosphate. Hence, ATP synthase is both an ion channel protein and enzyme. The synthesis
reaction is driven by the proton flow, which forces the rotation of a part of the enzyme; the ATP synthase is a rotary
mechanical motor. Bacteria may also have a version of this enzyme, where it, of course, is embedded in the cell
membrane.
During electron transport within the mitochondria (during cellular respiration) or chloroplast (during photosynthesis)
(discussed in the Concept Metabolism (Advanced) concept), a proton gradient is formed when protons are pumped
across the membrane by active transport. These hydrogen ions flow back across the membrane by facilitated
diffusion through ATP synthase, releasing energy which is then used to convert ADP to ATP (by phosphorylation).
Chemiosmosis is the diffusion of protons across the biological membrane through ATP synthase, due to a proton
gradient that forms across the membrane during electron transport.
Vocabulary

ATP synthase: Ion channel and enzyme complex; chemically bonds a phosphate group to ADP, producing
ATP as H+ ions flow through the ion channel.
chemiosmosis: Process in cellular respiration or photosynthesis which produces ATP; uses the energy of
hydrogen ions diffusing through ATP synthase.
chemiosmotic potential: A difference in concentration of hydrogen ions across a membrane within the
mitochondrion or chloroplast; established using energy from an electron transport chain; also known as a
chemiosmotic gradient.
electrochemical gradient: Difference across a membrane due to both a chemical force and an electrical force;
drives the movement of ions across the membrane.
membrane potential: The voltage difference across a membrane; the basis for the conduction of nerve
impulses along the cell membrane of neurons.
oxidative phosphorylation: A metabolic process that uses energy released by the oxidation of nutrients to
produce adenosine triphosphate (ATP).
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proton gradient: Gradient established from a higher concentration of protons on one side of a membrane
compared to the other side of the membrane.
proton motive force: The storing of energy due to a combination of a proton gradient and a voltage gradient
across a membrane.
resting potential: The membrane potential of a cell/neuron at rest; the membrane potential of an unstimulated
neuron.
voltage: The difference in electrical potential energy of two points/areas; electrical potential energy that is
caused by a separation of opposite charges.
Summary

The voltage across a membrane is the membrane potential and the membrane potential of a cell at rest is the
resting potential.
The electrochemical gradient is composed of a chemical force (the ions concentration gradient) and an
electrical force (the effect of the membrane potential on the ions movement).
Chemiosmosis is the diffusion of protons across the biological membrane through ATP synthase, due to a
proton gradient that forms across the membrane.
Explore More

Use this resource to answer the questions that follow. Gradients at http://www.youtube.com/watch?v=kQ_3mI0WY
i0

MEDIA
Click image to the left or use the URL below.
URL: http://www.ck12.org/flx/render/embeddedobject/139344

1. Why does an electrochemical gradient form across a cell membrane?

2. Why are positive ions attracted to the inside of a cell?
3. How do ions flow in and out of a cell?
Review

1. Define the electrochemical gradient.

2. Describe the role of ATP synthase.
3. What is chemiosmosis?

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Chapter 3. Cell Biology - Advanced

3.32 Exocytosis and Endocytosis - Advanced

Explain how different types of active transport occur.
Compare endocytosis and exocytosis.

What does a cell "eat"?

Is it possible for objects larger than a small molecule to be engulfed by a cell? Of course it is. This image
depicts a cancer cell being attacked by a cell of the immune system. Cells of the immune system consistently
destroy pathogens by essentially "eating" them. Just as cells can bring substances into the cell, they can also export
substances out of the cell.
Vesicles and Active Transport

Some molecules or particles are just too large to pass through the plasma membrane or to move through a transport
protein. So cells use two other active transport methods to move these macromolecules (large molecules) into or
out of the cell. Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma
membrane. There are two types of vesicle transport, endocytosis and exocytosis. These processes are active transport
mechanisms, therefore energy is required.
Endocytosis and Exocytosis

Endocytosis is the process of capturing a substance or particle from outside the cell by engulfing it with the cell
membrane. The membrane folds over the substance and it becomes completely enclosed by the membrane. At this
point a membrane-bound sac, or vesicle pinches off and moves the substance into the cytosol. There are two main
kinds of endocytosis:
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Phagocytosis or "cellular eating," occurs when the dissolved materials enter the cell. The plasma membrane
engulfs the solid material, forming a phagocytic vesicle.
Pinocytosis or "cellular drinking," occurs when the plasma membrane folds inward to form a channel allowing
dissolved substances to enter the cell, as shown in Figure 3.41. When the channel is closed, the liquid is
encircled within a pinocytic vesicle.

FIGURE 3.41
Transmission electron microscope image
of brain tissue that shows pinocytotic vesicles. Pinocytosis is a type of endocytosis.

Exocytosis describes the process of vesicles fusing with the plasma membrane and releasing their contents to the
outside of the cell, as shown in Figure 3.42. Exocytosis occurs when a cell produces substances for export, such as a
protein, or when the cell is getting rid of a waste product or a toxin. Newly made membrane proteins and membrane
lipids are moved to the plasma membrane by exocytosis.

FIGURE 3.42
Illustration of the two types of vesicle
transport, exocytosis and endocytosis.
Endocytosis and exocytosis are types of
vesicle transport that carry very large
molecules across the cell membrane.

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Chapter 3. Cell Biology - Advanced

For a detailed animation on cellular secretion, see http://vcell.ndsu.edu/animations/constitutivesecretion/first.htm .

FIGURE 3.43
Illustration of an axon releasing dopamine
by exocytosis.

Receptor-Mediated Endocytosis

Some substances are internalized after binding to a membrane-bound receptor. This process is known as receptormediated endocytosis (RME). RME is a process by which cells internalize molecules by endocytosis. This occurs
by the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the molecules
being internalized. After the binding of a ligand to the plasma membrane-spanning receptors, a signal is sent through
the membrane, leading to membrane coating by the protein clathrin, and formation of a membrane invagination. The
receptor and its ligand are then internalized in clathrin-coated vesicles. RME is also known as clathrin-dependent
endocytosis, named after the clathrin protein that accumulates on the internal segment of membrane that will form
a vesicle.
Clathrin-mediated endocytosis is further discussed at http://www.youtube.com/watch?v=-ZFnO5RY1cU .

MEDIA
Click image to the left or use the URL below.
URL: http://www.ck12.org/flx/render/embeddedobject/139338

Homeostasis and Cell Function

Homeostasis refers to the balance, or equilibrium within the cell or a body. It is an organisms ability to keep a
constant internal environment. Keeping a stable internal environment requires constant adjustments as conditions
change inside and outside the cell. The adjusting of systems within a cell is called homeostatic regulation. Because
the internal and external environments of a cell are constantly changing, adjustments must be made continuously
to stay at or near the set point (the normal level or range). Homeostasis is a dynamic equilibrium rather than an
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unchanging state. The cellular processes discussed in this lesson all play an important role in homeostatic regulation.
More concerning homeostasis will be presented in additional concepts.
Vocabulary

clathrin: A protein that plays a major role in the formation of coated vesicles.
clathrin-dependent endocytosis: Endocytosis in which the inward budding of plasma membrane vesicles
containing proteins with receptor sites specific to the molecules being internalized; also known as receptormediated endocytosis.
endocytosis: The cellular process of capturing a material/substance from outside the cell by vesicle formation.
exocytosis: The cellular process of secreting materials by vesicle fusion.
homeostasis: The process of maintaining a stable environment inside a cell or an entire organism.
phagocytosis: The process of engulfing and breaking down pathogens and other unwanted substances.
pinocytosis: Type of vesicle transport that occurs when the plasma membrane folds inward to form a channel,
allowing dissolved substances to enter the cell.
receptor-mediated endocytosis (RME): Endocytosis in which the inward budding of plasma membrane
vesicles containing proteins with receptor sites specific to the molecules being internalized; also known as
clathrin-dependent endocytosis.
Summary

Endocytosis and exocytosis are active transport mechanisms in which large molecules enter and leave the cell
inside vesicles.
In endocytosis, a substance or particle from outside the cell is engulfed by the cell membrane. The membrane
folds over the substance and it becomes completely enclosed by the membrane. There are two main kinds of
endocytosis: pinocytosis and phagocytosis.
Review

1. What is the difference between endocytosis and exocytosis?

2. Why is pinocytosis a form of endocytosis?
3. Are vesicles involved in passive transport?

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Chapter 3. Cell Biology - Advanced

3.33 Cell Communication - Advanced

Describe what is meant by cell communication.

What does adrenaline do?

Adrenaline, or epinephrine, is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels,
dilates air passages, and participates in the fight-or-flight response of the sympathetic nervous system. Adrenaline is
produced in the adrenal medulla of the adrenal gland. So how does it effect processes all over the body?

The Language of Cells

To survive and grow, cells need to be able to communicate with their neighboring cells and be able to detect change
in their environment. "Talking" with neighboring cells is even more important to a cell if it is part of a multicellular
organism. Cell communication, or cell signaling, is the basis of development, tissue repair, and immunity. It is
also necessary for normal tissue homeostasis. The trillions of cells that make up your body need to be able to
communicate with each other to allow your body to grow, and to keep you alive and healthy. The same is true for
any organism. Cell signaling is part of a complex system of communication that governs basic cellular activities and
coordinates cell actions. Cell signaling is a major area of research in biology today. Defects in cell signaling are
associated with diseases such as cancer, autoimmunity, and diabetes.
Recently scientists have discovered that many different cell types, from bacteria to plants, use similar types of
communication pathways, or cell-signaling mechanisms. This suggests that cell-signaling mechanisms evolved long
before the first multicellular organism did.
For cells to be able to signal to each other, a few things are needed:
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a signal,
a cell receptor, which is a protein usually on the plasma membrane, but can be found inside the cell,
a response to the signal.
Cells that are communicating may be right next to each other or far apart. In juxtacrine signaling, also known
as contact-dependent signaling, two adjacent cells must make physical contact in order to communicate. Cell
communication may also occur over short distances, which is known as paracrine signaling, or over large distances,
which is known as endocrine signaling.
The type of chemical signal a cell will send differs depending on the distance the message needs to go. For example,
hormones, ions, and neurotransmitters are all types of signals that are sent depending on the distance the message
needs to go. Endocrine signals are hormones, produced by endocrine organs. These signals travel through the blood
stream to reach all parts of the body.
The target cell then needs to be able to recognize the signal. Chemical signals are received by the target cell on
receptor proteins. Most receptor proteins are found associated with the plasma membrane, but some are also found
inside the cell. Receptor proteins are very specific for only one particular signal molecule, much like a lock that
recognizes only one key. Therefore, a cell has lots of receptor proteins to recognize the large number of cell signal
molecules. There are three stages to sending and receiving a cell "message:" reception, transduction, and response.
1. Reception occurs when a ligand binds to its receptor.
2. Through transduction, the signal is then internalized. The ligand does not have to be internalized for this
process to occur.
3. The response may initiate a cascade of reactions including the activation/deactivation of enzymes and/or an
alternation in gene transcription.
Vocabulary

cell receptor: Specialized proteins that take part in communication between the cell and the extracellular
environment; often are integral membrane proteins.
cell signaling: Part of a complex communication system that governs basic cellular activities and coordinates
cell actions.
endocrine signaling: Cell communication over long distances.
hormone: A chemical messenger molecule.
juxtacrine signaling: Cell communication via direct contact.
neurotransmitter: Chemical messages which are released at the synapse; relay the message/signal onto the
next neuron or other type of cell.
paracrine signaling: Cell communication over short distances.
Summary

Cell communication or cell signaling describes how cells share information.

Cell communication usually begins when a molecule (a ligand) binds to its receptor.
Cell communication can be over short or long distances.
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Explore More

Use this resource to answer the questions that follow.

The Fight or Flight Response at http://learn.genetics.utah.edu/content/begin/cells/cellcom/ .
1.
2.
3.
4.

Describe the role of signaling molecules.

How do signaling molecules travel throughout the body?
Describe the results of a stress response.
Based on this video, what is your definition of cell communication?

Review

1. Define cell communication.

2. Compare juxtacrine, paracrine and endocrine signaling.
3. Describe the process of cell signaling.

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3.34 Signal Receptors - Advanced

Describe the types of signal receptors used in cell communication.

What pulls a signal in from vast distances?

Some sort of signal receptor. This receptor is usually a protein embedded in the cell membrane. Once the signal
binds to its receptor, some sort of outcome is initiated - the signal is transferred to the cell. This may be from an ion
channel opening or some other process.
Signal Receptors

A signal molecule must bind to its receptor to initiate a response. Receptors are proteins that bind to their signal
molecule either externally (cell-surface receptors) or internally (nuclear receptors) within the cytoplasm or nucleus.
This process is known as signal transduction, and the internal activator is the second messenger. Once a ligand
binds to its receptor, a series of reactions are initiated.
Cell-Surface Receptors

Cell-surface receptors are integral membrane proteinsthey reach right through the phospholipid bilayer, spanning
from the outside to the inside of the cell. These receptor proteins are specific for just one signal molecule. The
signaling molecule acts as a ligand when it binds to a receptor protein. A ligand is a small molecule that binds to a
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larger molecule. Signal molecule binding causes the receptor protein to undergo a conformational change (a change
in shape). At this point the receptor protein can interact with another molecule. The ligand (the signal molecule)
itself does not pass through the plasma membrane.
In eukaryotic cells, most of the intracellular proteins that are activated by a ligand binding to a receptor protein are
enzymes. Receptor proteins are named after the type of enzyme that they interact with inside the cell. These enzymes
include G proteins and protein kinases, likewise there are G-protein-linked receptors and tyrosine kinase receptors.
A kinase is a protein involved in phosphorylation. Tyrosine kinase receptors bind many polypeptide growth factors,
cytokines, and hormones. Once the ligand is bound, these receptors specifically phosphorylate tyrosine amino acids,
activating the signal transduction process inside the cell.
A G-protein linked receptor is a receptor that works with the help of a protein called a G-protein. A G-protein gets
its name from the molecule to which it is attached, guanosine triphosphate (GTP), or guanosine diphosphate (GDP).
The GTP molecule is similar to ATP.
Second Messengers

Once G proteins or protein kinase enzymes are activated by a receptor protein - after the ligand binds to its receptor they create molecules called second messengers. A second messenger is a small molecule that starts a change inside
a cell in response to the binding of a specific signal to a receptor protein. Some second messenger molecules include
small molecules called cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine
monophosphate (cGMP). Calcium ions (Ca2+ ) also act as secondary messengers. Secondary messengers are a part
of signal transduction pathways.
Nuclear Receptors

Some receptors bind the ligand internally. In this case, the ligand must be able to enter the cell. These receptors
usually interact with steroid and thyroid hormones. Once the ligand binds to the receptor, the receptor becomes
activated, and the whole complex enters the nucleus, hence these receptors are known as nuclear receptors. In the
nucleus, the activated receptor acts as a transcription factor, where it interacts with other proteins to regulate the
expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism.
Vocabulary

cell-surface receptor: Specialized integral membrane protein that take part in communication between the
cell and the extracellular environment.
cyclic adenosine monophosphate (cAMP, cyclic AMP): A second messenger important in many biological
processes; used for intracellular signal transduction, such as transferring into cells the effects of hormones.
G protein (guanine nucleotide-binding protein): Guanine nucleotide-binding proteins; a family of proteins
involved in transmitting chemical signals outside the cell, causing changes inside the cell.
G-protein linked receptor: A large protein family of transmembrane receptors that bind molecules outside
the cell and activate signal transduction pathways inside the cell; also known as G protein coupled receptors
and seven-transmembrane domain receptors.
kinase: A type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to
specific substrates, a process known as phosphorylation.
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FIGURE 3.44
Two-component signal transduction system. This process begins with the stimulus binding to its receptor. Shown here
is a cell-surface receptor. The signal in
then transduced to the inside of the cell.

ligand: A small molecule that binds to a larger molecule.

nuclear receptor: A class of proteins found within cells that are responsible for binding steroid and thyroid
hormones; may act as a transcription factor.
second messenger: A molecule that relays a signal from a receptor on the cell surface to target molecules
inside the cell.
signal transduction: The process that occurs when an extracellular signaling molecule activates a cell surface
receptor, which then alters intracellular molecules creating a response.
transcription factor: A protein involved in regulating gene expression; usually bound to a cis-regulatory
element on the DNA; also known as a regulatory protein or a trans-acting factor.
tyrosine kinase receptor: Family of cell surface receptors for many polypeptide growth factors, cytokines,
and hormones; specifically phosphorylate tyrosine amino acids; also known as receptor tyrosine kinases.
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Summary

Signal transduction begins with a ligand binding to its receptor.

Cell-surface receptors bind a ligand outside of the cell and internalize the signal, acting through a second
messenger.
Nuclear receptors bind a ligand inside the cell and change transcription of genes by acting as a transcription
factor.
Explore More

Use this resource to answer the questions that follow.

G-Protein Coupled Hormone Signal Transduction at http://www.youtube.com/watch?v=A3AUhMCE9n0

MEDIA
Click image to the left or use the URL below.
URL: http://www.ck12.org/flx/render/embeddedobject/139340

1.
2.
3.
4.
5.
6.
7.

What is a peptide hormone?

How does the message from a peptide hormone enter the cell?
Describe the structure of a G-protein.
Describe the function of an activated G-protein.
What is the function of an active phospholipase C?
What are the two second messengers discussed in this process?
What is the role of an active protein kinase C?

Review

1. Compare and contrast cell-surface and nuclear receptors.

2. What is a second messenger?
3. What are nuclear receptors functions?

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3.35 Signal Transduction - Advanced

Outline the process of signal transduction.

How is information transduced from the outside of the cell?

It starts with the ligand binding its receptor. Once the signal is internalized, the second messenger then begins a
cascade of reactions that can greatly change the behavior of the cell.

Signal Transduction

A signal-transduction pathway is the signaling mechanism by which a cell changes a signal on its surface into a
specific response inside the cell. This process begins when a ligand binds to its receptor. The receptor may either be
a cell-surface receptor in the cell membrane or a nuclear receptor in the cytoplasm of the cell. See DNA responds
to signals from outside the cell at http://www.dnaftb.org/35/animation.html to see James Darnall speak about signal
transduction.
Signal transduction most often involves an ordered sequence of chemical reactions inside the cell which is carried out
by enzymes and other molecules. In many signal transduction processes, the number of proteins and other molecules
participating in these events increases as the process progresses from the binding of the signal. A "signal cascade"
begins. Think of a signal cascade as a chemical domino-effect inside the cell, in which one domino knocks over two
dominoes, which in turn knock over four dominoes, and so on. The advantage of this type of signaling to the cell is
that the message from one little signal molecule can be greatly amplified and have a dramatic effect.
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Chapter 3. Cell Biology - Advanced

FIGURE 3.45
How a G-protein linked receptor works
with the help of a G-protein.

G Proteins

G proteins (guanine nucleotide-binding proteins) are a family of GTPases involved in transmitting chemical
signals outside the cell, and causing changes inside the cell. When a ligand binds to a G protein coupled receptor,
an intracellular domain of the receptor activates a G protein. The G protein then activates additional intracellular
pathways, resulting in an altered intracellular environment. G proteins function as molecular switches. When they
bind guanosine triphosphate (GTP), they are on, and, when they bind guanosine diphosphate (GDP), they are off.

G Protein Coupled Receptors and Cyclic AMP

G protein linked receptors are only found in higher eukaryotes, including yeast, plants, and animals. Your senses
of sight and smell are dependent on G-protein linked receptors. The ligands that bind to these receptors include
light-sensitive compounds, odors, hormones, and neurotransmitters. The ligands for G-protein linked receptors
come in different sizes, from small molecules to large proteins. When a ligand binds to the receptor, it causes a
conformational change in the receptor, which allows it to act as a guanine nucleotide exchange factor. The receptor
can then activate an associated G-protein by exchanging its bound GDP for a GTP. The G-proteins subunit,
together with the bound GTP, can then dissociate from the and subunits to further affect intracellular signaling
proteins.
Many times the activated G-protein-linked receptor will then activate cyclic AMP (cAMP), which acts as the second
messenger in initiating a cascade of reactions.
The process of how a G-protein linked receptor works is outlined in Figure 3.46.

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FIGURE 3.46
How a G-protein linked receptor works
with the help of a G-protein.

In panel

C, the second messenger cAMP can be

seen moving away from the enzyme.

G-Protein Linked Receptors

A. A ligand such as a hormone (small, purple molecule) binds to the G protein-linked receptor (red molecule).
Before ligand binding, the inactive G-protein (yellow molecule) has GDP bound to it.
B. The receptor changes shape and activates the G-protein and a molecule of GTP replaces the GDP.
C. The G-protein moves across the membrane then binds to and activates the enzyme (green molecule). This then
triggers the next step in the pathway to the cells response. After activating the enzyme, the G-protein returns
to its original position. The second messenger of this signal transduction is cAMP, as shown in C.

The sensing of the external and internal environments at the cellular level relies on signal transduction. Defects
in signal transduction pathways can contribute or lead to many diseases, including cancer and heart disease. This
highlights the importance of signal transductions to biology and medicine.
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G-protein linked receptors are also involved in the phosphatidylinositol (PI) signal pathway. In this pathway, PI
can be phosphorylated to form phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2 ) and
phosphatidylinositol trisphosphate (PIP3 ), which are collectively called phosphoinositides. These molecules play
important roles in lipid signaling, cell signaling and membrane trafficking.
Signal Response

In response to a signal, a cell may change activities in the cytoplasm or in the nucleus that include the switching on
or off of genes. Changes in metabolism, continued growth, movement, or death are some of the cellular responses
to signals that require signal transduction.
Gene activation leads to other effects, since the protein products of many of the responding genes include enzymes
and factors that increase gene expression. Gene expression factors produced as a result of a cascade can turn on
even more genes. Therefore one stimulus can trigger the expression of many genes, and this in turn can lead to the
activation of many complex events. In a multicellular organism these events include the increased uptake of glucose
from the blood stream (stimulated by insulin), and the movement of neutrophils to sites of infection (stimulated by
bacterial products). The set of genes and the order in which they are activated in response to stimuli are often called
a genetic program.
FIGURE 3.47
Signal transduction pathways. Ras (upper middle section) activates a number of
pathways but an especially important one
seems to be the mitogen-activated protein
kinases (MAPK). MAPK transmit signals
downstream to other protein kinases and
gene regulatory proteins. Note that many
of these pathways are initiated when a
signal binds to its receptor outside the
cell. Most pathways end with altered gene
regulation and cell proliferation. The p53
tumor suppressor protein is shown at the
lower section of the figure stimulating p21.
The complexity of the pathways demonstrate the significant role these play in the
cell.

Vocabulary

cyclic adenosine monophosphate (cAMP, cyclic AMP): A second messenger important in many biological
processes; used for intracellular signal transduction, such as transferring into cells the effects of hormones.
G protein (guanine nucleotide-binding protein): Guanine nucleotide-binding proteins; a family of proteins
involved in transmitting chemical signals outside the cell, causing changes inside the cell.
G protein-linked receptor: A large protein family of transmembrane receptors that bind molecules outside
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the cell and activate signal transduction pathways inside the cell; also known as G protein coupled receptors
and seven-transmembrane domain receptors.
GTPase: A large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP) to
guanosine diphosphate (GDP).
second messenger: A molecule that relays a signal from a receptor on the cell surface to target molecules
inside the cell.
signal-transduction: The process that occurs when an extracellular signaling molecule activates a cell surface
receptor, which then alters intracellular molecules creating a response.
Summary

Signal transduction occurs when a ligand binds its receptor and alters intracellular conditions.
Often the signal is transducer from the outside of the cell to the inside.
This process usually involves G-protein linked receptors and cyclic AMP.
Explore More

Use this resource to answer the questions that follow.

Signal Transduction Pathways at http://www.youtube.com/watch?v=qOVkedxDqQo

MEDIA
Click image to the left or use the URL below.
URL: http://www.ck12.org/flx/render/embeddedobject/139339

1.
2.
3.
4.
5.

Describe a general signal transduction pathway.

What is meant by a phosphorylation cascade?
How is adenyl cyclase activated? What is the role of adenyl cyclase?
Describe the role of cAMP.
How is protein kinase activated? What is the role of protein kinase?

Review

1. Define G-protein.
2. Describe the process of signal transduction, focusing on the roles of G-protein linked receptors and cyclic
AMP.

Summary
The cell is the smallest unit of structure and function of all living organisms. Cell Biology focuses on significant
aspects of the cell from its structure to its division. Some organisms contain just one cell, and others contain
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Chapter 3. Cell Biology - Advanced

trillions. Some have a nucleus with DNA, others do not. Some have many organelles, others do not. But all cells
are surrounded by a cell membrane. And it is this semipermeable membrane that determines what can enter and
leave the cell. All cells need energy, and for many organisms, this energy comes from photosynthesis and cellular
respiration. All cells come from preexisting cells through the process of cell division, which can produce a new
prokaryotic organism. The cell cycle, which includes mitosis, defines the life of an eukaryotic cell.

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