Week 6.1 Advanced

www.ck12.org 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 movethrough the phospholipid bilayer. Other times, substances need the assistance of a protein, like a channel protein orsome 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 ofa 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. Thisfeature allows a cell to control the transport of materials, as dictated by the cells function. The permeability of amembrane 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 anorganism 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. Forexample, hydrophobic (water-hating) molecules, such as carbon dioxide (CO2) and oxygen (O2), can easily pass

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FIGURE 3.33A selectively permeable, or semiperme-able, membrane allows certain moleculesthrough, but not others.

through the lipid bilayer, but ions such as calcium (Ca2+) and polar molecules such as water (H2O) cannot. Thehydrophobic interior of the phospholipid bilayer does not allow ions or polar molecules through because they arehydrophilic, or water loving. In addition, large molecules such as sugars and proteins are too big to pass throughthe phospholipid bilayer. Transport proteins within the membrane allow these molecules to cross the membrane intoor out of the cell. This way, polar molecules avoid contact with the nonpolar interior of the membrane, and largemolecules are moved through large pores.

Every cell is contained within a membrane punctuated with transport proteins that act as channels or pumps to let inor force out certain molecules. The purpose of the transport proteins is to protect the cells internal environment andto 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 noenergy 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 oftransport proteins. The third way, called active transport, requires that the cell uses energy to pull in or pump outcertain molecules and ions. Active transport involves proteins known as pumps. The fourth way is through vesicletransport, in which large molecules are moved across the membrane in bubble-like sacks that are made from piecesof 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 con-stant internal environment. Keeping a stable internal environment requires constant adjustments as conditions changeinside and outside the cell. The adjusting of systems within a cell is referred to as homeostatic regulation. Becausethe internal and external environments of a cell are constantly changing, adjustments must be made continuously tostay at or near the normal proportions of all internal substances. This involves continual adjustments in transport ofsubstances across the cell membrane. Homeostasis is a dynamic equilibrium rather than an unchanging state. Thecellular processes discussed in the cell transport (passive and active transport) concepts all play an important role inhomeostatic regulation.

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Vocabulary

concentration gradient: Difference in the concentrations of a molecule across two distinct areas, such as acell membrane.

diffusion: The movement of molecules from an area of high concentration of the molecules to an area with alower 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 energyby the cell.

selectively permeable: The ability to allow only certain molecules to cross the plasma membrane; semiper-meable.

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, isachieved. The process of moving from areas of high amounts of a substance to areas of low amounts of the samesubstance is called diffusion.

Diffusion

Passive transport is a way that small molecules or ions move across the cell membrane without input of energy bythe cell. The three main kinds of passive transport are diffusion (or simple diffusion), osmosis, and facilitated diffu-sion. Simple diffusion and osmosis do not involve transport proteins. Facilitated diffusion requires the assistance ofproteins.

Diffusion is the movement of molecules from an area of high concentration of the molecules to an area with a lowerconcentration. For cell transport, diffusion is the movement of small molecules across the cell membrane. Thedifference in the concentrations of the molecules in the two areas is called the concentration gradient. The kineticenergy of the molecules results in random motion, causing diffusion. In simple diffusion, this process proceedswithout the aid of a transport protein. it is the random motion of the molecules that causes them to move from anarea of high concentration to an area with a lower concentration.

Diffusion will continue until the concentration gradient has been eliminated. Since diffusion moves materials froman 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 bothdirections.

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 includeions and small hydrophilic molecules, such as glucose, and macromolecules, including proteins and RNA. Examplesof molecules that can easily diffuse across the plasma membrane include carbon dioxide and oxygen gas. Thesemolecules 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 suchimportance to the cell that it is given a special name, osmosis.

FIGURE 3.34Molecules move from an area of highconcentration to an area of lower concen-tration until an equilibrium is met. Themolecules continue to cross the mem-brane at equilibrium, but at equal rates inboth directions.

Vocabulary

concentration gradient: Difference in the concentrations of a molecule across two distinct areas, such as acell membrane.

diffusion: The movement of molecules from an area of high concentration of the molecules to an area with alower concentration.

equilibrium: State of equal concentration of a molecule, such as on both sides of the cell membrane.


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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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 ofthem 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 willhappen 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, C12H22O11) 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 thesolvent (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. Justlike the first cup, the sugar is the solute, and the water is the solvent. But now you have two mixtures of differentsolute concentrations. In comparing two solutions of unequal solute concentration, the solution with the highersolute concentration is hypertonic, and the solution with the lower concentration is hypotonic. Solutions of equalsolute concentration are isotonic. The first sugar solution is hypotonic to the second solution. The second sugarsolution is hypertonic to the first.

You now add the two solutions to a beaker that has been divided by a selectively permeable membrane. The poresin the membrane are too small for the sugar molecules to pass through, but are big enough for the water moleculesto 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 ofwater now exists across the membrane. Water molecules will move from the side of higher water concentration tothe 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 havinga larger concentration of a substance on the outside of a cell than is found within the cells themselves. A hypotonicsolution 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 higherconcentration to an area of lower concentration. Water moves into and out of cells by osmosis. If a cell is in ahypertonic solution, the solution has a lower water concentration than the cell cytosol does, and water moves outof the cell until both solutions are isotonic. Cells placed in a hypotonic solution will take in water across theirmembrane 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 ahypotonic 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, acell without a cell wall will lose water to the environment, shrivel, and probably die. In a hypertonic solution, a cellwith a cell wall will lose water too. The plasma membrane pulls away from the cell wall as it shrivels, a processcalled plasmolysis. Animal cells tend to do best in an isotonic environment, plant cells tend to do best in a hypotonicenvironment. 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, thewall helps maintain the cells water balance. Osmotic pressure is the main cause of support in many plants. When aplant cell is in a hypotonic environment, the osmotic entry of water raises the turgor pressure exerted against the cellwall until the pressure prevents more water from coming into the cell. At this point the plant cell is turgid ( Figure3.36). 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 (hyper-tonic). The water from inside the potato moves out of the potato cells to the salt solution, which causes the potatocells to lose turgor pressure. The more concentrated the salt solution, the greater the difference in the size and weightof the potato slice after plasmolysis.

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FIGURE 3.35Unless an animal cell (such as the redblood cell in the top panel) has an adap-tation that allows it to alter the osmoticuptake of water, it will lose too much waterand shrivel up in a hypertonic environ-ment. If placed in a hypotonic solution,water molecules will enter the cell causingit to swell and burst. Plant cells (bottompanel) become plasmolyzed in a hyper-tonic solution, but tend to do best in ahypotonic environment. Water is stored inthe central vacuole of the plant cell.

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

The action of osmosis can be very harmful to organisms, especially ones without cell walls. For example, if asaltwater 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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MEDIAClick image to the left or use the URL below.URL: http://www.ck12.org/flx/render/embeddedobject/253

Controlling Osmosis

Organisms that live in a hypotonic environment such as freshwater, need a way to prevent their cells from takingin too much water by osmosis. A contractile vacuole is a type of vacuole that removes excess water from acell. Freshwater protists, such as the paramecia shown in Figure 3.37, have a contractile vacuole. The vacuole issurrounded 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 cellwhen full and release the water into the environment.

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

Vocabulary

contractile vacuole: An organelle found in freshwater protists involved in osmoregulation; pumps excesswater out of a cell.

hypotonic: In comparing two solutions of unequal solute concentration, the solution with the higher soluteconcentration.

hypertonic: In comparing two solutions of unequal solute concentration, the solution with the lower soluteconcentration.

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 throughosmosis; 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 concentrationgradient. 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, orfacilitating 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 diffusionis a type of passive transport. Even though facilitated diffusion involves transport proteins (and is essentially atransport process), it can still be considered passive transport because the solute is moving down the concentrationgradient, and no input of energy is required. Facilitated diffusion utilizes proteins known as uniporters. A uniportercan 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 tothe 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 themembrane, and allows certain molecules or ions to diffuse across the membrane. Channel proteins, gated channelproteins, 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 smallions through quickly. Water channel proteins allow water to diffuse across the membrane at a very fast rate. Ionchannel 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 themembrane. Gated channels have a binding site that is specific for a given molecule or ion. A stimulus causesthe "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 bya chemical signal which causes them to open and allow sodium ions into the cell. Glucose molecules are too big todiffuse through the plasma membrane easily, so they are moved across the membrane through gated channels. Inthis way glucose diffuses very quickly across a cell membrane, which is important because many cells depend onglucose 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. Carrierproteins are involved in passive and active transport. A model of a channel protein and carrier proteins is shown inFigure 3.38.

FIGURE 3.38Facilitated diffusion through the cell mem-brane. Channel proteins and carrier pro-teins are shown (but not a gated-channelprotein). Water molecules and ions movethrough channel proteins. Other ions ormolecules are also carried across the cellmembrane by carrier proteins. The ion ormolecule binds to the active site of a car-rier protein. The carrier protein changesshape, and releases the ion or moleculeon the other side of the membrane. Thecarrier protein then returns to its originalshape.

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 cellfunctions. Because they are polar, these ions do not diffuse through the membrane. Instead they move throughion channel proteins where they are protected from the hydrophobic interior of the membrane. Ion channels allowthe formation of a concentration gradient between the extracellular fluid and the cytosol. Ion channels are veryspecific 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 stimulisuch as electrical or chemical signals.

Vocabulary

carrier protein: A transport protein that is specific for an ion, molecule, or group of substances; carries theion 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 smallions 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 themembrane.

ion channel: A channel protein that transports ions across the membrane by facilitated diffusion.


transport protein: A protein that completely spans the membrane, and allows certain molecules or ions todiffuse across the membrane; channel proteins, gated channel proteins, and carrier proteins are three types oftransport proteins that are involved in facilitated diffusion.

uniporter: An integral membrane protein that is involved in facilitated diffusion; can be either a channel or acarrier protein.

Summary

Facilitated diffusion is the diffusion of solutes through transport proteins in the plasma membrane. Channelproteins, gated channel proteins, and carrier proteins are three types of transport proteins that are involved infacilitated diffusion.

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Explore More

Membrane Channels at http://phet.colorado.edu/en/simulation/membrane-channels .


Review

1. Compare and contrast simple diffusion and facilitated diffusion. For each type of diffusion, give an exampleof 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. Howwould 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 concentrationgradient, active transport pumps molecules and ions against a concentration gradient. Sometimes an organism needsto transport something against a concentration gradient, such as specific ions, or glucose and amino acids. Theonly way this can be done is through active transport which uses transport proteins and energy that is produced bycellular respiration (ATP) or through an electrochemical gradient. In active transport, the particles move acrossa cell membrane from a lower concentration to a higher concentration. Active transport is the energy-requiringprocess of pumping molecules and ions across membranes "uphill" against a gradient. The active transport ofsmall molecules or ions across a cell membrane is generally carried out by transport proteins that are found in themembrane. These transport proteins have receptor regions that bind to specific molecules and transport them intothe cell. Larger molecules such as starch can also be actively transported across the cell membrane by vesiculartransport processes.

During active transport, specialized integral membrane proteins recognize the substance and allows it access. Es-sentially this process is forcing a ion or molecule to cross the membrane when normally it would not. Moving asubstance against its concentration gradient is known as primary active transport, and the proteins involved in itas "pumps". This process uses the energy of ATP. In secondary active transport, energy from an electrochemicalgradient is used to transport substances. This process involves pore-forming proteins that form channels through thecell membrane.

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Primary Active Transport

Primary active transport involves an integral membrane protein and the energy from ATP to transport moleculesacross a membrane. This type of transport is mainly done by ATPases. ATPases are a class of enzymes that catalyzethe dephosphorylation of adenosine triphosphate into adenosine diphosphate (ADP) and a free phosphate ion. Thisreaction 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. Thispump will be discussed in the Active Transport: The Sodium-Potassium Pump (Advanced) concept. Other sources ofenergy for primary active transport are redox energy and photon energy (light energy). Redox energy is used in themitochondrial electron transport chain during cellular respiration. In this transport, the reduction energy of NADHis used to move protons across the inner mitochondrial membrane against their concentration gradient. An exampleof primary active transport using photon energy occurs during photosynthesis. During photosynthesis, proteins usethe energy of photons to create a proton gradient across the chloroplast thylakoid membrane. That energy is used topump H+ ions into the thylakoid.

Secondary Active Transport

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

Antiport and Symport

The difference between the two types of cotransport depends on the direction of transport of the molecules. A systemin which one substance moves in one direction while cotransporting another substance in the other direction is calledantiport. Symport is transport of two substrates in the same direction across the membrane. The protein involvedin 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 substancesis transported in the direction of their concentration gradient,and the energy derived is used to transport the secondsubstance against its concentration gradient. Thus, energy stored in the electrochemical gradient of an ion isused 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 ownelectrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are movedagainst their concentration gradients, fueled by ATP. In symport, one substance moves down the electrochemicalgradient, allowing the other molecule(s) to move against its concentration gradient. One substance moves byfacilitated 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; re-quires energy.

antiport: The secondary active transport process of transporting two or more different molecules or ionsacross a phospholipid membrane in opposite directions.

antiporter: An integral membrane protein involved in secondary active transport; transports two or moredifferent 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 adenosinediphosphate (ADP) and a free phosphate ion.

cotransport: The simultaneous or sequential transport of more than one molecule or ion across biologicalmembranes; 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 gradi-ent, allowing a different substance to move against its own electrochemical gradient; also known as cotrans-port.

symport: The secondary active transport process of transporting two or more different molecules or ionsacross a phospholipid membrane in the same direction.

symporter: An integral membrane protein involved in secondary active transport; transports two or moredifferent 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 ofhigher 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 transportproteins 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-active-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 nervecells function will be the focus of another concept. However, active transport processes play a significant role in thefunction 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 movesolutes against the concentration gradient (from low concentration to high concentration), with energy input fromATP. As in other types of cellular activities, ATP supplies the energy for most active transport. One way ATP powersactive transport is by transferring a phosphate group directly to a carrier protein. This may cause the carrier proteinto change its conformation, which moves the molecule or ion to the other side of the membrane. An example ofthis 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 theplasma membrane of animal cells. The sodium-potassium pump is found in the plasma membrane of almost everyhuman cell and is common to all cellular life. It helps maintain resting potential, especially in neurons following anerve 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 3.39The sodium-potassium pump systemmoves sodium and potassium ionsagainst large concentration gradients. Itmoves two potassium ions into the cellwhere potassium levels are high, andpumps three sodium ions out of the celland into the extracellular fluid.

2. ATP is hydrolyzed resulting in adenosine diphosphate (ADP) and an inorganic phosphate. The free phosphatephosphorylates the sodium-potassium pump.

3. A conformational change in the pump exposes the Na+ ions to the outside. The phosphorylated form of thepump 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 itsprevious 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 boundK+ 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-ONQFjpQ (13:53) and http://www.youtube.com/watch?v=ye3rTjLCvAU (6:48).



Vocabulary

Na+/K+-ATPase: An active transport carrier protein/a transmembrane ATPase; moves sodium and potassiumions against large concentration gradients; the sodium-potassium pump.

resting potential: The membrane potential of a cell/neuron at rest; the membrane potential of an unstimulatedneuron.

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sodium-potassium pump: An active transport carrier protein/a transmembrane ATPase; moves sodium andpotassium 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. Are there more sodium ions on the outside of cells or the inside?2. Are there more potassium ions on the outside of cells or the inside?3. What is the hydrolysis of ATP?4. In what type of cells can a sodium-potassium pump be found?5. 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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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 itall 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 ionsin the cytosol. This results in a relatively negative charge on the inside of the membrane, and a positive charge onthe outside. This difference in charges causes a voltage to exist across the membrane. Voltage is electrical potentialenergy that is caused by a separation of opposite charges, in this case across the membrane. The voltage acrossa membrane is the membrane potential. Membrane potential is very important for the conduction of electricalimpulses along nerve cells. The membrane potential of a cell at rest is known as its resting potential, and isdiscussed 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 comparedto outside the cell. This resulting membrane potential favors the movement of positively charged ions (cations) intothe cell, and the movement of negative ions (anions) out of the cell. So, there are two forces that drive the diffusionof 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 anelectrochemical gradient.

The electrochemical gradient determines the direction an ion moves by diffusion or active transport across a mem-brane. In mitochondria and chloroplasts, proton gradients are used to generate a chemiosmotic potential that isalso 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 highlevels of potassium ions (K+) within the cell (intracellular). The sodium-potassium pump moves three Na+ ions outof the cell and brings two K+ ions into the cell. This essentially removes one positive charge from the intracellularspace. The resulting membrane potential is known as the resting potential.

FIGURE 3.40This diagram shows how ions main-tain the membrane potential. Thesodium-potassium pump is shown in themembrane, 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. Themembrane may be that of a cell or organelle or other sub cellular compartment. The electrochemical potential arisesfrom 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), and3. 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 biologicalmembranes. Transmembrane ATPases are often involved in maintaining ion gradients. The Na+/K+ ATPase usesATP 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 isestablished through active transport involving proton pumps. The proton gradient is used during photosynthesisand cellular respiration to generate a chemiosmotic potential, or proton motive force. This potential energy is usedfor the synthesis of ATP by oxidative phosphorylation. The proton gradient can also be used to store energy for heatproduction and flagellar rotation.

The energy held within the proton gradient can be used to synthesize ATP. ATP synthase is a transmembrane enzymethat provides energy for the cell to use by producing ATP. The protein has two distinct regions, F0 and F1. The F0domain is embedded within the membrane, while the F1 domain is above the membrane, inside the matrix of themitochondria, or the stroma of the chloroplast. The F0 region is the proton pore, allowing hydrogen ions to diffuseacross the membrane. The F1 region of the protein has ATP synthesis activity, catalyzing the formation of ATP fromADP and inorganic phosphate. Hence, ATP synthase is both an ion channel protein and enzyme. The synthesisreaction is driven by the proton flow, which forces the rotation of a part of the enzyme; the ATP synthase is a rotarymechanical motor. Bacteria may also have a version of this enzyme, where it, of course, is embedded in the cellmembrane.

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 pumpedacross the membrane by active transport. These hydrogen ions flow back across the membrane by facilitateddiffusion 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 protongradient that forms across the membrane during electron transport.

Vocabulary

ATP synthase: Ion channel and enzyme complex; chemically bonds a phosphate group to ADP, producingATP as H+ ions flow through the ion channel.

chemiosmosis: Process in cellular respiration or photosynthesis which produces ATP; uses the energy ofhydrogen ions diffusing through ATP synthase.

chemiosmotic potential: A difference in concentration of hydrogen ions across a membrane within themitochondrion or chloroplast; established using energy from an electron transport chain; also known as achemiosmotic 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 nerveimpulses along the cell membrane of neurons.

oxidative phosphorylation: A metabolic process that uses energy released by the oxidation of nutrients toproduce adenosine triphosphate (ATP).

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proton gradient: Gradient established from a higher concentration of protons on one side of a membranecompared 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 gradientacross a membrane.

resting potential: The membrane potential of a cell/neuron at rest; the membrane potential of an unstimulatedneuron.

voltage: The difference in electrical potential energy of two points/areas; electrical potential energy that iscaused 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 theresting potential.

The electrochemical gradient is composed of a chemical force (the ions concentration gradient) and anelectrical 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 aproton 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_3mI0WYi0


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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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 imagedepicts a cancer cell being attacked by a cell of the immune system. Cells of the immune system consistentlydestroy pathogens by essentially "eating" them. Just as cells can bring substances into the cell, they can also exportsubstances 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 transportprotein. So cells use two other active transport methods to move these macromolecules (large molecules) into orout of the cell. Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasmamembrane. There are two types of vesicle transport, endocytosis and exocytosis. These processes are active transportmechanisms, 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 cellmembrane. The membrane folds over the substance and it becomes completely enclosed by the membrane. At thispoint a membrane-bound sac, or vesicle pinches off and moves the substance into the cytosol. There are two mainkinds of endocytosis:

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Phagocytosis or "cellular eating," occurs when the dissolved materials enter the cell. The plasma membraneengulfs the solid material, forming a phagocytic vesicle.

Pinocytosis or "cellular drinking," occurs when the plasma membrane folds inward to form a channel allowingdissolved substances to enter the cell, as shown in Figure 3.41. When the channel is closed, the liquid isencircled within a pinocytic vesicle.

FIGURE 3.41Transmission electron microscope imageof brain tissue that shows pinocytotic vesi-cles. Pinocytosis is a type of endocyto-sis.

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

FIGURE 3.42Illustration of the two types of vesicletransport, exocytosis and endocytosis.Endocytosis and exocytosis are types ofvesicle transport that carry very largemolecules across the cell membrane.

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

FIGURE 3.43Illustration of an axon releasing dopamineby exocytosis.

Receptor-Mediated Endocytosis

Some substances are internalized after binding to a membrane-bound receptor. This process is known as receptor-mediated endocytosis (RME). RME is a process by which cells internalize molecules by endocytosis. This occursby the inward budding of plasma membrane vesicles containing proteins with receptor sites specific to the moleculesbeing internalized. After the binding of a ligand to the plasma membrane-spanning receptors, a signal is sent throughthe membrane, leading to membrane coating by the protein clathrin, and formation of a membrane invagination. Thereceptor and its ligand are then internalized in clathrin-coated vesicles. RME is also known as clathrin-dependentendocytosis, named after the clathrin protein that accumulates on the internal segment of membrane that will forma vesicle.

Clathrin-mediated endocytosis is further discussed at http://www.youtube.com/watch?v=-ZFnO5RY1cU .


Homeostasis and Cell Function

Homeostasis refers to the balance, or equilibrium within the cell or a body. It is an organisms ability to keep aconstant internal environment. Keeping a stable internal environment requires constant adjustments as conditionschange inside and outside the cell. The adjusting of systems within a cell is called homeostatic regulation. Becausethe internal and external environments of a cell are constantly changing, adjustments must be made continuouslyto 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 vesiclescontaining proteins with receptor sites specific to the molecules being internalized; also known as receptor-mediated 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 membranevesicles containing proteins with receptor sites specific to the molecules being internalized; also known asclathrin-dependent endocytosis.

Summary

Endocytosis and exocytosis are active transport mechanisms in which large molecules enter and leave the cellinside vesicles.

In endocytosis, a substance or particle from outside the cell is engulfed by the cell membrane. The membranefolds over the substance and it becomes completely enclosed by the membrane. There are two main kinds ofendocytosis: 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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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 isproduced 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 changein their environment. "Talking" with neighboring cells is even more important to a cell if it is part of a multicellularorganism. Cell communication, or cell signaling, is the basis of development, tissue repair, and immunity. It isalso necessary for normal tissue homeostasis. The trillions of cells that make up your body need to be able tocommunicate with each other to allow your body to grow, and to keep you alive and healthy. The same is true forany organism. Cell signaling is part of a complex system of communication that governs basic cellular activities andcoordinates cell actions. Cell signaling is a major area of research in biology today. Defects in cell signaling areassociated with diseases such as cancer, autoimmunity, and diabetes.

Recently scientists have discovered that many different cell types, from bacteria to plants, use similar types ofcommunication pathways, or cell-signaling mechanisms. This suggests that cell-signaling mechanisms evolved longbefore 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 knownas contact-dependent signaling, two adjacent cells must make physical contact in order to communicate. Cellcommunication 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 messageneeds to go. Endocrine signals are hormones, produced by endocrine organs. These signals travel through the bloodstream 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 onreceptor proteins. Most receptor proteins are found associated with the plasma membrane, but some are also foundinside the cell. Receptor proteins are very specific for only one particular signal molecule, much like a lock thatrecognizes only one key. Therefore, a cell has lots of receptor proteins to recognize the large number of cell signalmolecules. 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 extracellularenvironment; often are integral membrane proteins.

cell signaling: Part of a complex communication system that governs basic cellular activities and coordinatescell 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 thenext 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


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

1. Describe the role of signaling molecules.2. How do signaling molecules travel throughout the body?3. Describe the results of a stress response.4. 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 signalbinds to its receptor, some sort of outcome is initiated - the signal is transferred to the cell. This may be from an ionchannel 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 signalmolecule 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 ligandbinds 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, spanningfrom the outside to the inside of the cell. These receptor proteins are specific for just one signal molecule. Thesignaling 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 changein 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 areenzymes. Receptor proteins are named after the type of enzyme that they interact with inside the cell. These enzymesinclude 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 getsits 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 insidea cell in response to the binding of a specific signal to a receptor protein. Some second messenger molecules includesmall molecules called cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosinemonophosphate (cGMP). Calcium ions (Ca2+) also act as secondary messengers. Secondary messengers are a partof signal transduction pathways.

Nuclear Receptors

Some receptors bind the ligand internally. In this case, the ligand must be able to enter the cell. These receptorsusually interact with steroid and thyroid hormones. Once the ligand binds to the receptor, the receptor becomesactivated, and the whole complex enters the nucleus, hence these receptors are known as nuclear receptors. In thenucleus, the activated receptor acts as a transcription factor, where it interacts with other proteins to regulate theexpression 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 thecell and the extracellular environment.

cyclic adenosine monophosphate (cAMP, cyclic AMP): A second messenger important in many biologicalprocesses; 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 proteinsinvolved 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 outsidethe cell and activate signal transduction pathways inside the cell; also known as G protein coupled receptorsand seven-transmembrane domain receptors.

kinase: A type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, tospecific substrates, a process known as phosphorylation.

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FIGURE 3.44Two-component signal transduction sys-tem. This process begins with the stim-ulus binding to its receptor. Shown hereis a cell-surface receptor. The signal inthen 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 thyroidhormones; may act as a transcription factor.

second messenger: A molecule that relays a signal from a receptor on the cell surface to target moleculesinside the cell.

signal transduction: The process that occurs when an extracellular signaling molecule activates a cell surfacereceptor, which then alters intracellular molecules creating a response.

transcription factor: A protein involved in regulating gene expression; usually bound to a cis-regulatoryelement 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


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


1. What is a peptide hormone?2. How does the message from a peptide hormone enter the cell?3. Describe the structure of a G-protein.4. Describe the function of an activated G-protein.5. What is the function of an active phospholipase C?6. What are the two second messengers discussed in this process?7. 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 acascade 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 aspecific response inside the cell. This process begins when a ligand binds to its receptor. The receptor may either bea cell-surface receptor in the cell membrane or a nuclear receptor in the cytoplasm of the cell. See DNA respondsto signals from outside the cell at http://www.dnaftb.org/35/animation.html to see James Darnall speak about signaltransduction.

Signal transduction most often involves an ordered sequence of chemical reactions inside the cell which is carried outby enzymes and other molecules. In many signal transduction processes, the number of proteins and other moleculesparticipating 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 twodominoes, which in turn knock over four dominoes, and so on. The advantage of this type of signaling to the cell isthat the message from one little signal molecule can be greatly amplified and have a dramatic effect.

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

G Proteins

G proteins (guanine nucleotide-binding proteins) are a family of GTPases involved in transmitting chemicalsignals 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 intracellularpathways, resulting in an altered intracellular environment. G proteins function as molecular switches. When theybind 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 sensesof sight and smell are dependent on G-protein linked receptors. The ligands that bind to these receptors includelight-sensitive compounds, odors, hormones, and neurotransmitters. The ligands for G-protein linked receptorscome in different sizes, from small molecules to large proteins. When a ligand binds to the receptor, it causes aconformational change in the receptor, which allows it to act as a guanine nucleotide exchange factor. The receptorcan 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 signalingproteins.

Many times the activated G-protein-linked receptor will then activate cyclic AMP (cAMP), which acts as the secondmessenger 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 3.46How a G-protein linked receptor workswith the help of a G-protein. In panelC, the second messenger cAMP can beseen 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 returnsto 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. Defectsin signal transduction pathways can contribute or lead to many diseases, including cancer and heart disease. Thishighlights 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, PIcan be phosphorylated to form phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2) andphosphatidylinositol trisphosphate (PIP3), which are collectively called phosphoinositides. These molecules playimportant 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 onor off of genes. Changes in metabolism, continued growth, movement, or death are some of the cellular responsesto signals that require signal transduction.

Gene activation leads to other effects, since the protein products of many of the responding genes include enzymesand factors that increase gene expression. Gene expression factors produced as a result of a cascade can turn oneven more genes. Therefore one stimulus can trigger the expression of many genes, and this in turn can lead to theactivation of many complex events. In a multicellular organism these events include the increased uptake of glucosefrom the blood stream (stimulated by insulin), and the movement of neutrophils to sites of infection (stimulated bybacterial products). The set of genes and the order in which they are activated in response to stimuli are often calleda genetic program.

FIGURE 3.47Signal transduction pathways. Ras (up-per middle section) activates a number ofpathways but an especially important oneseems to be the mitogen-activated proteinkinases (MAPK). MAPK transmit signalsdownstream to other protein kinases andgene regulatory proteins. Note that manyof these pathways are initiated when asignal binds to its receptor outside thecell. Most pathways end with altered generegulation and cell proliferation. The p53tumor suppressor protein is shown at thelower section of the figure stimulating p21.The complexity of the pathways demon-strate the significant role these play in thecell.

Vocabulary

cyclic adenosine monophosphate (cAMP, cyclic AMP): A second messenger important in many biologicalprocesses; 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 proteinsinvolved 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 receptorsand seven-transmembrane domain receptors.

GTPase: A large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP) toguanosine diphosphate (GDP).

second messenger: A molecule that relays a signal from a receptor on the cell surface to target moleculesinside the cell.

signal-transduction: The process that occurs when an extracellular signaling molecule activates a cell surfacereceptor, 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


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


1. Describe a general signal transduction pathway.2. What is meant by a phosphorylation cascade?3. How is adenyl cyclase activated? What is the role of adenyl cyclase?4. Describe the role of cAMP.5. 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 significantaspects of the cell from its structure to its division. Some organisms contain just one cell, and others contain

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

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Week 6.1 Advanced

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