Ch05 Lecture-Cell Membranes and Signaling-1

7/31/2019 Ch05 Lecture-Cell Membranes and Signaling-1

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Cell Membranes and

Signaling

5


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Concept 5.1 Biological Membranes Have a Common Structure

and Are Fluid

A membranes structure and functionsare determined by its constituents: lipids,

proteins, and carbohydrates.

The general structure of membranes isknown as the fluid mosaic model.

Phospholipids form a bilayer which is like

a lake in which a variety of proteinsfloat.


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Figure 5.1 Membrane Molecular Structure


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and Are Fluid

Lipids form the hydrophobic core of themembrane.

Most lipid molecules are phospholipidswith tworegions:

Hydrophilic regionselectrically chargedheads that associate with water molecules

Hydrophobic regions

nonpolar fatty acid

tails that do not dissolve in water


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and Are Fluid

A bilayeris formed when the fatty acidtails associate with each other and the

polarheads face the aqueous

environment.

Bilayer organization helps membranes fuse

during vesicle formation and phagocytosis.


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and Are Fluid

Membranes may differ in lipid compositionasthere are many types of phospholipids.

Phospholipids may differ in:

Fatty acid chain length

Degree of saturation Kinds of polar groups present


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and Are Fluid

Two important factors in membrane fluidity:

Lipid compositiontypes of fatty acids can

increase or decrease fluidity

Temperaturemembrane fluidity decreases

in colder conditions


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and Are Fluid

Biological membranes contain proteins, withvarying ratios of phospholipids.

Peripheral membrane proteins lackhydrophobic groups and are not embedded

in the bilayer.

Integral membrane proteins are partlyembedded in the phospholipid bilayer.

C C S


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and Are Fluid

Anchored membrane proteinshave lipidcomponents that anchor them in the bilayer.

Proteins are asymmetrically distributed on theinner and outer membrane surfaces.

A transmembrane protein extends through

the bilayer on both sides, and may havedifferent functions in its external andtransmembrane domains.

C t 5 1 Bi l i l M b H C St t


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and Are Fluid

Some membrane proteins can move withinthe phosopholipid bilayer, while others are

restricted.

Proteins inside the cell can restrict movement

of membrane proteins, as can attachments

to the cytoskeleton.



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and Are Fluid

Plasma membrane carbohydrates arelocated on the outer membrane and can

serve as recognition sites.

Glycolipida carbohydrate bonded to alipid

Glycoprotein

a carbohydrate bondedto a protein



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and Are Fluid

Membranes are constantly changing byforming, transforming into other types,

fusing, and breaking down.

Though membranes appear similar, there

are major chemical differences among the

membranes of even a single cell.

C t 5 2 S S b t C C th M b b


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Concept 5.2 Some Substances Can Cross the Membrane by

Diffusion

Biological membranes allow somesubstances, and not others, to pass.

This is known as selectivepermeability.

Two processes of transport:

Passive transport does not requiremetabolic energy.

Active transport requires input of

metabolic energy.



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Diffusion

Passive transport of a substance canoccur through two types of diffusion:

Simple diffusionthrough the

phospholipid bilayer

Facilitated diffusionthrough channel

proteins or aided by carrier proteins



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Diffusion

Diffusion is the process of randommovement toward equilibrium.

Speed of diffusion depends on three

factors:

Diameterof the moleculessmaller

molecules diffuse faster

Temperatureof the solutionhighertemperatures lead to faster diffusion

Concept 5 2 Some S bstances Can Cross the Membrane b


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Diffusion

The concentration gradientin thesystemthe greater the concentration

gradient in a system, the faster a

substance will diffuse

A higher concentration inside the cell

causes the solute to diffuse out, and a

higher concentration outside causes thesolute to diffuse in, for many molecules.

Concept 5 2 Some Substances Can Cross the Membrane by


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Diffusion

Simple diffusion takes place through thephospholipid bilayer.

A molecule that is hydrophobic and

soluble in lipids can pass through themembrane.

Polar molecules do not pass through

they are not soluble in the hydrophilicinterior and form bonds instead in theaqueous environment near themembrane.



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Diffusion

Osmosis is the diffusion of water acrossmembranes.

It depends on the concentration of solute

molecules on either side of themembrane.

Water passes through special membranechannels.


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Diffusion of water from

HIGH concentrationof water to

LOW concentrationof water

across a

semi-permeable

membrane

Figure 5 3A Osmosis Can Modify the Shapes of Cells


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Figure 5.3A Osmosis Can Modify the Shapes of Cells

Figure 5 3B Osmosis Can Modify the Shapes of Cells


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Figure 5.3B Osmosis Can Modify the Shapes of Cells

Figure 5 3C Osmosis Can Modify the Shapes of Cells


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Figure 5.3C Osmosis Can Modify the Shapes of Cells


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SIMPLE DIFFUSION IS NOT ENOUGH



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Diffusion

FACILITATED DIFFUSION

Channel proteins are integral membraneproteins that form channels across the

membrane.

Substances can also bind to carrier

proteins to speed up diffusion.


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Porin monomer

-pleated sheets

Bacterialoutermembrane

aquaporin =water channel in bacteria

function through

conformational change =

protein changes shape

Examples

H2O

H2O

CHANNEL PROTEIN



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Diffusion

Ion channelsare a type ofchannel

proteinmost

are gated, andcan be opened

or closed to ion

passage.



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Diffusion

Carrier proteins in the

membrane facilitatediffusion by binding

substances.

Glucose transporters are

carrier proteins in

mammalian cells.

Glucose molecules bind to

the carrier protein and

cause the protein to

change shapeit

releases glucose on the

other side of the

membrane.


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Biological Systems Still Need a Way of

Maintaining Differences Across a Membrane

AGAINST the Concentration Gradient

THIS IS ACTIVE TRANSPORT

Concept 5 3 Some Substances Require Energy to Cross the


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Concept 5.3 Some Substances Require Energy to Cross the

Membrane

Active transport requires the input ofenergy to move substances against theirconcentration gradients.

Active transport is used to overcomeconcentration imbalances that are

maintained by proteins in the

membrane.

Concept 5 3 Some Substances Require Energy to Cross the


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Membrane

The energy source for active transport isoften ATP.

Active transport is directionaland moves

a substance against its concentrationgradient.

A substance moves in the direction of the

cells needs, usually by means of aspecific carrier protein.



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Membrane

Two types of active transport:

Primary active transport involveshydrolysis of ATP for energy.

Secondary active transport uses theenergy from an ion concentration

gradient, or an electrical gradient.


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Membrane

The sodium

potassium (Na+

K+

) pumpis an integral membrane protein thatpumps Na+ out of a cell and K+ in.

One molecule of ATP moves two K+ andthree Na+ ions.

Figure 5.7 Primary Active Transport: The SodiumPotassium Pump


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g y p p



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Concept 5.3 Some Substances Require Energy to Cross theMembrane

Secondary active transport uses energythat is regained, by letting ions move

across the membrane withtheirconcentration gradients.

Secondary active transport may begin

with passive diffusion of a few ions, or

may involve a carrier protein thattransports both a substance and ions.


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Secondary Active Transport


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Concept 5.4 Large Molecules Cross the Membrane via Vesicles

Macromolecules are too large or toocharged to pass through biological

membranes and instead pass through

vesicles.

To take up or to secrete macromolecules,

cells must use endocytosisor

exocytosis.

Figure 7.22


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Solutes

Pseudopodium

Food orother particle

Foodvacuole

CYTOPLASM

Plasmamembrane

Vesicle

Receptor

Ligand

Coat proteins

Coated

pit

Coatedvesicle

EXTRACELLULARFLUID

Phagocytosis Pinocytosis Receptor-Mediated Endocytosis


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Concept 5.4 Large Molecules Cross the Membrane via Vesicles

Receptor

mediated endocytosisdepends on receptors to bind tospecific molecules (theirligands).

The receptors are integral membraneproteins located in regions called coatedpits.

The cytoplasmic surface is coated byanother protein (often clathrin).

Concept 5.5 The Membrane Plays a Key Role in a Cells


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p y yResponse to Environmental Signals

Cells can respond to many signals if theyhave a specific receptor for that signal.

A signal transduction pathway is a

sequence of molecular events andchemical reactions that lead to a cellular

response, following the receptors

activation by a signal.


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SWITCH TO OTHER POWER POINT



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p y yResponse to Environmental Signals

Cells are exposed to many signals andmay have different responses:

Autocrine signals affect the same cells

that release them.

Paracrine signals diffuse to and affectnearby cells.

Hormones travel to distant cells.

Figure 5.10 Chemical Signaling Concepts


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Response to Environmental Signals

Only cells with the necessary receptorscan respond to a signalthe target cell

must be able to senseit and respondtoit.

A signal transduction pathway involves a

signal, a receptor, and a response.

Figure 5.11 Signal Transduction Concepts


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A common mechanism of signaltransduction is allosteric regulation.

This involves an alteration in a proteins

shape as a result of a molecule bindingto it.

A signal transduction pathway mayproduce short or long term responses.



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A signal molecule, orligand, fits into athree-dimensional site on the receptorprotein.

Binding of the ligand causes the receptorto change its three-dimensional shape.

The change in shape initiates a cellularresponse.

Figure 5.12 A Signal Binds to Its Receptor


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Concept 5.5 The Membrane Plays a Key Role in a CellsS


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Ligands are generally not metabolizedfurther, but their binding may expose an

active site on the receptor.

Binding is reversible and the ligand canbe released, to end stimulation.

An inhibitor, orantagonist, can bind inplace of the normal ligand.

Concept 5.5 The Membrane Plays a Key Role in a CellsR t E i t l Si l


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Receptors can be classified by theirlocation in the cell.

This is determined by whether or not their

ligand can diffuse through themembrane.



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Cytoplasmic receptorshave ligands, suchas estrogen, that are small or nonpolarand can diffuse across the membrane.

Membrane receptorshave large or polarligands, such as insulin, that cannot

diffuse and must bind to a

transmembrane receptor at anextracellular site.



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Receptors are also classified by theiractivity:

Ion channel receptors

Protein kinase receptors

G proteinlinked receptors



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Ion channel receptors, orgated ionchannels, change their three-dimensional shape when a ligand binds.

The acetylcholine receptor, a ligand-gated sodium channel, binds

acetylcholine to open the channel and

allow Na+

to diffuse into the cell.



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Protein kinase receptors change theirshape when a ligand binds.

The new shape exposes or activates a

cytoplasmic domain that has catalytic(protein kinase) activity.

Figure 5.13 A Protein Kinase Receptor


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Concept 5.5 The Membrane Plays a Key Role in a CellsResponse to En ironmental Signals


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Protein kinases catalyze the followingreaction:

ATP + protein ADP + phosphorylated

protein

Each protein kinase has a specific target

protein, whose activity is changed whenit is phosphorylated.

Concept 5.5 The Membrane Plays a Key Role in a CellsResponse to Environmental Signals


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Ligands binding to G protein

linkedreceptors expose a site that can bind toa membrane protein, a G protein.

The G protein is partially inserted in thelipid bilayer, and partially exposed on

the cytoplasmic surface.



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Many G proteins have three subunits andcan bind three molecules:

The receptor

GDP and GTP, used for energy transfer

An effector protein to cause an effect in

the cell



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The activated G protein

linked receptorexchanges a GDP nucleotide bound to

the G protein for a higher energy GTP.

The activated G protein activates theeffector protein, leading to signal

amplification.

Figure 5.14 A G ProteinLinked Receptor


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Concept 5.6 Signal Transduction Allows the Cell to Respond to ItsEnvironment


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Environment

Signal activation of a specific receptorleads to a cellular response, which is

mediated by a signal transduction

pathway.

Signaling can initiate a cascadeof proteininteractionsthe signal can then be

amplifiedand distributedto causedifferent responses.



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Environment

A second messenger is an intermediarybetween the receptor and the cascadeof responses.

In the fight-or-flight response, epinephrine(adrenaline) activates the liver enzymeglycogen phosphorylase.

The enzyme catalyzes the breakdown ofglycogen to provide quick energy.



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Environment

Researchers found that the cytoplasmicenzyme could be activated by the

membrane-bound epinephrine in broken

cells, as long as all parts were present.

They discovered that another molecule

delivered the message from the first

messenger,

epinephrine, to theenzyme.

Figure 5.15 The Discovery of a Second Messenger (Part 1)


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Figure 5.15 The Discovery of a Second Messenger (Part 2)


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Environment

The second messenger was laterdiscovered to be cyclic AMP (cAMP).

Second messengers allow the cell to

respond to a single membrane eventwith many events inside the celltheydistributethe signal.

They amplifythe signal by activatingmore than one enzyme target.

Figure 5.16 The Formation of Cyclic AMP


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Environment

Signal transduction pathways involvemultiple stepsenzymes may be either

activated or inhibited by other enzymes.

In liver cells, a signal cascade beginswhen epinephrine stimulates a G

proteinmediated protein kinase

pathway.



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Environment

Epinephrine binds to its receptor andactivates a G protein.

cAMP is produced and activates protein

kinase A

it phosphorylates two otherenzymes, with opposite effects:

Inhibition

Activation

Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)


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Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)


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Environment

Inhibitionprotein kinase A inactivatesglycogen synthase through

phosphorylation, and prevents glucosestorage.

ActivationPhosphorylase kinase isactivated when phosphorylated and is

part of a cascade that results in theliberation of glucose molecules.



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Environment

Signal transduction ends after the cell

respondsenzymes convert each

transducer back to its inactive precursor.

The balance between the regulatingenzymes and the signal enzymes

determines the cells response.

Figure 5.18 Signal Transduction Regulatory Mechanisms


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Cells can alter the balance of enzymes in

two ways:

Synthesis or breakdown of the enzyme

Activation or inhibition of the enzymes

by other molecules



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Cell functions change in response to

environmental signals:

Opening of ion channels

Alterations in gene expression

Alteration of enzyme activities

Answer to Opening Question


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p g

Caffeine is a large, polar molecule that

binds to receptors on nerve cells in the

brain.

Its structure is similar to adenosine, whichbinds to receptors after activity or stress

and results in drowsiness.

Caffeine binds to the same receptor, but

does not activate itthe result is that

the person remains alert.

Figure 5.19 Caffeine and the Cell Membrane (Part 1)


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Figure 5.19 Caffeine and the Cell Membrane (Part 2)


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Ch05 Lecture-Cell Membranes and Signaling-1