chapter 3 part i - edl€¦ · copyright © 2006 pearson education, inc., ... inc., publishing as...

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

The Cell


Cell Theory

� The cell is the basic structural and functional unit

of life

� Organismal activity depends on individual and

collective activity of cells

� Biochemical activities of cells are dictated by their

subcellular structures

� Continuity of life has a cellular basis

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Figure 3.2

Secretion being releasedfrom cell by exocytosis

Peroxisome

Ribosomes

Roughendoplasmicreticulum

Nucleus

Nuclear envelopeChromatin

Golgi apparatus

Nucleolus

Smooth endoplasmicreticulum

Cytosol

Lysosome

Mitochondrion

Centrioles

Centrosomematrix

Microtubule

Microvilli

Microfilament

Intermediatefilaments

Plasmamembrane


Cell Theory

Let’s see a video that the folks up at Harvard have made for

us

Which structures can you identify?

http://aimediaserver.com/studiodaily/harvard/harvard.swf


Cell Theory

� The Cell is the smallest “living” unit

� Disease is the loss of cellular homeostasis

� Over 200 cell types exist in the human body with

sizes ranging from 2 um to 1 meter (nerve cell)!

� Shape (structure) reflects function.

� E.g. flat epithelial cells act as barriers for

protection.


Cell Theory

Cells are composed of three principle areas

(regions)

� Plasma Membrane

� Cytoplasm

� Nucleus


Plasma Membrane (Cell Membrane)

� Defines the extent of the cell

� Separates intracellular fluids from extracellular

fluids

� Encloses all of the cell organelles

� Plays a dynamic role in cellular activity


Fluid Mosaic Model

� Plasma membrane is a double layer (bilayer) of

lipids with imbedded, dispersed proteins

� A bilayer consists of phospholipids, cholesterol,

and glycolipids

� Proteins are trapped in the bilayer:

Extra/intracellular regions are hydrophilic

Transdomain regions are hydrophobic


Fluid Mosaic Model

The Lipids of the Bilayer

� Phospholipids have hydrophobic and hydrophilic

bipoles

� Glycolipids are lipids with bound

carbohydrate

� Cholesterol


Fluid Mosaic Model

The bilayer is self-orienting (forms by itself)

-self assembly into spheres

-seals quickly if “opened” (to a degree)

The majority of the membrane lipids are unsaturated (phosphatidyl choline) which “kinks” the tails

This Increases

Membrane Fluidity!!


Fluid Mosaic Model

Figure 3.3


Functions of Membrane Proteins

� Transport

� Enzymatic activity

� Receptors for signal

transduction

Figure 3.4.1


Functions of Membrane Proteins

� Intercellular adhesion

� Cell-cell recognition

� Attachment to

cytoskeleton and

extracellular matrix

Figure 3.4.2


Plasma Membrane Surfaces

� Differ in the kind and amount of lipids they contain

� Glycolipids are found only in the outer membrane surface

-5% of total membrane lipid

-Polarization via the sugar group

� 20% of all membrane lipid is cholesterol

-Wedges it rings between the phospholipid

(nonpolar) tails

-Increases fluidity of the membrane


Lipid Rafts

� Make up 20% of the outer membrane surface

� Composed of sphingolipids and cholesterol

� Create stable, less fluid, areas

� Are concentrating platforms for cell-signaling

molecules


Membrane Proteins

� Two types: Integral & Peripheral

� Integral: Span the lipid bilayer

They often are transmembrane proteins and

protrude on both sides of the membrane


Peripheral Proteins

� Not embedded in the lipid bilayer

� Attach to integral proteins or membrane lipids


Glycoproteins

� Proteins supporting sugar groups

� Includes many of the integral proteins that extend

into the extracellular space


Glycocalyx

� Carbohydrate rich area at the cell surface

� Formed from glycolipids and glycoproteins

� Useful in identifying cell types on the basis of the

sugar types surrounding the cell


Specializations of the Plasma Membrane:Microvilli

� Minute extensions & recessions of the plasma

membrane that increase surface area

� Found on the surface of absorptive cells, e.g.

intestine, kidneys, etc…

� Have a core made of actin

to support “villi” structure


Membrane Junctions

� Bind cells together

� Factors include:

� Glycoproteins (e.g. adhesion proteins),

� Tight junction – impermeable junction that encircles the cell

� Desmosome – anchoring junction scattered along the sides of cells

� Gap junction – a nexus that allows chemical substances to pass between cells


Membrane Junctions: Tight Junction

Figure 3.5a

-Integral membrane proteins in the plasma membrane of adjacent

cells that fuse together

-Help prevent molecules from passing through the extracellular

space between adjacent cells


Membrane Junctions: Desmosome

Figure 3.5b

-Plaque on the cytoplasmic face of the plasma membrane

-Adjacent cells are held together by cadherins (thin filaments) that

extend from the plaques and interdigitate in the

intercellular space like a zipper

-Intermediate filaments form part of the cytoskeleton and extend

from the plaques on the opposite sides of a cell (e.g. guy wires)

-Abundant in tissues subjected to great mechanical stress


Membrane Junctions: Gap Junction

Figure 3.5c

-E.g. connexons: transmembrane proteins that form a hollow

cylinder that connects adjacent cells

-Varying connexons result in varying selectivity

-Things like ions, sugars, and small molecules can pass


Function of the Plasma Membrane

� Plasma membrane is a selective (or differentially)

permeable barrier.

� E.g. allows some substances to pass and blocks

others

� Plasma membrane moves things across by:

� Active processes: require ATP to cross P.M.

� Passive processes: require no energy from cell


Passive Membrane Transport: Diffusion

� Diffusion is the tendency of molecules and ions to

scatter evenly throughout the environment

� Molecules move from areas of high concentration

to areas of low concentration

� Kinetic energy is the driving force.

� Thus, size and temperature influence rate of

diffusion



� The plasma membrane is a physical barrier to free

diffusion due to its hydrophobic core.

� Molecules will diffuse through the plasma

membrane if the molecule is:

� lipid soluble

� can pass through membrane channels

� assisted by a carrier molecule



� Simple diffusion – nonpolar and lipid-soluble

substances

� Diffuse directly through the lipid bilayer

� E.g. O2 & CO2 (opposite gradients), fat-soluble

vitamins

� Diffuse through channel proteins



� Facilitated diffusion

� Transported substance binds to protein carriers in

the plasma membrane and is ferried across or

moves through water filled protein channels

� E.g. sugars, amino acids, ions


Carrier Proteins

� Are integral transmembrane proteins

� Show specificity for certain polar molecules,

including sugars and amino acids, too large for

simple diffusion and facilitated diffusion

� Molecules move down a concentration gradient

� Molecules are shielded from the hydrophobic

plasma membrane by integral membrane proteins


Channels

� Transmembrane proteins that transport ions &

water through aqueous channels across the plasma

membrane

� Pore size and net charge of the amino acids lining

the channel determines selectivity

� Leaky channels: always open

� Gated channels: open & close by chemical or

electrical signals


Diffusion Through the Plasma Membrane

Figure 3.7

Extracellular fluid

Cytoplasm

Lipid-

solublesolutes

Lipidbilayer

Lipid-insolublesolutes

Watermolecules

Small lipid-insoluble

solutes

(a) Simple diffusiondirectly through the

phospholipid bilayer

(c) Channel-mediatedfacilitated diffusion

through a channelprotein; mostly ionsselected on basis of

size and charge

(b) Carrier-mediated facilitateddiffusion via protein carrier

specific for one chemical; bindingof substrate causes shape changein transport protein

(d) Osmosis, diffusionthrough a specific

channel protein(aquaporin) or through the lipid

bilayer


Passive Membrane Transport: Osmosis

� Occurs when the concentration of a solvent is

different on opposite sides of a membrane

� Diffusion of water across a semipermeable

membrane

� Osmolarity – total concentration of solute particles

in a solution

� Tonicity – how a solution affects cell volume


Effect of Membrane Permeability on Diffusion and Osmosis

Figure 3.8a



Figure 3.8b

�[solute] must be equal on both sides of membrane



� In a cell, however, as water diffuses into the cell,

an equilibrium is reached where the hydrostatic

pressure (back pressure exerted by the water

against the membrane) within the cell is equal to

its osmotic pressure



� Tonicity: the ability of a solution to change the

shape, or tone, of a cell by altering its internal

water volume


Effects of Solutions of Varying Tonicity

� Isotonic – solutions with the same solute concentration as that of the cytosol

� Hypertonic – solutions having greater solute concentration than that of the cytosol

� Hypotonic – solutions having lesser solute concentration than that of the cytosol

RBC in Isotonic Solution RBC in Hypertonic Solution

RBC in Hypotonic Solution


Effects of Solutions of Varying Tonicity

� Thus, water moves towards greater solute

concentration

� Osmosis continues until osmotic and hydrostatic

pressures acting at the plasma membrane are equal


Active Transport (e.g. solute pumps)

� Uses ATP to move solutes (e.g. Na+, K+, Ca++)

“uphill” against concentration gradients and across

a membrane

� Requires carrier proteins


Active Transport

� Two types of Active Transport distinguished by

the source of energy used

� Primary Active Transport: Uses ATP

� Secondary Active Transport: Substance pumped

against its gradient can do “work” as it leaks

back in.

� E.g. Coupled transport: more than one

type of substrate at a time.

� E.g. Na/K ATPase pump


Cytoplasm

Extracellular fluidK+ is released andNa+ sites are ready tobind Na+ again; the

cycle repeats.

CellADP

Phosphorylation

causes theprotein tochange its shape.

Concentration gradientsof K+ and Na+

The shape change

expels Na+ to the outside, and extracellular K+ binds.

Loss of phosphate

restores the originalconformation of thepump protein.

K+ binding triggers

release of thephosphate group.

Binding of cytoplasmicNa+ to the pump protein

stimulates phosphorylationby ATP.Na+

Na+

Na+

Na+Na+

K+K+

K+

K+

Na+

Na+

Na+

ATP

P

P

Na+

Na+Na+

K+

K+

P

Pi

K+

K+


Primary Active Transport

� Na+/K+ ATPase pump

� The concentration gradients are 10-fold greater for

each element

� Required for muscle & nerve cells to functions and

for cells to maintain their fluid volume

� Na+& K+ leak across the membrane so the Na+/K+

pump is continuously working


Types of Active Transport

� Symport system – two substances are moved

across a membrane in the same direction

� Antiport system – two substances are moved

across a membrane in opposite directions


Seconday Active Transport

� Secondary active transport – use of an exchange

pump (such as the Na+-K+ ATPase pump)

indirectly to drive the transport of other solutes

…Or in other words

� A substance pumped against its gradient can do

“work” as it leaks back in.


Types of Active Transport

Figure 3.11


Vesicular Transport

� Transport of large particles and macromolecules

across plasma membranes

� Exocytosis – moves substance from the cell

interior to the extracellular space

� Endocytosis – enables large particles and

macromolecules to enter the cell

� Trafficking – moving within the cell

� All energized by ATP or GTP


Vesicular Transport

� Transcytosis – moving substances into, across, and

then out of a cell (across the cytosol).

� Which cells might frequently do this?

� Vesicular trafficking – moving substances from

one area in the cell to another

� Phagocytosis – pseudopods engulf solids and bring

them into the cell’s interior


Vesicular Transport

� Fluid-phase endocytosis – the plasma membrane

infolds, bringing extracellular fluid and solutes into

the interior of the cell

� Receptor-mediated endocytosis – clathrin-coated

pits provide the main route for endocytosis and

transcytosis

� Non-clathrin-coated vesicles – caveolae that are

platforms for a variety of signaling molecules


Exocytosis

Figure 3.12a

-Stimulated by a cell surface signal: e.g. binding of a hormone to

a membrane receptor

-Substance to be released is encased in a vesicle made of

phospholipid

-Docking via intertwining V-snare and Snare proteins


Clathrin-Mediated Endocytosis

Figure 3.13a

Recycling ofmembrane andreceptors (if present)

to plasma membrane

CytoplasmExtracellularfluid

Extracellularfluid

Plasmamembrane

Detachmentof clathrin-coatedvesicle

Clathrin-coatedvesicle

Uncoating

Uncoatedvesicle

Uncoatedvesiclefusing withendosome

To lysosomefor digestionand releaseof contents

Transcytosis

Endosome

Exocytosisof vesiclecontents

Clathrin-coated

pit

Plasma

membrane

Ingestedsubstance

Clathrinprotein

(a) Clathrin-mediated endocytosis

2

1

3


Clathrin-Mediated Endocytosis

� Main route for endocytosis & transcytosis of bulk solids, macromolecules, fluids

� Infolding of coated pits (clathrin protein) encloses the substance to be taken in.

� Once inside, clathrin is lost and vesicle fuses w/ the endosome for sorting:

� Recycled to plasma membrane

� Combined w/ lysosome and digested

� Exocytosis (via transcytosis)


Phagocytosis

Figure 3.13b

-Large material is engulfed by the cell

-Particles bind to receptors on the cell surface

-Cytoplasmic extensions (pseudopods) form and flow around

the particle

-The endocytotic vesicle is called a “phagosome”

-The phagosome fuses with the lysosome for digestion


Pinocytosis

� Fluid phase endocytosis

� Infolding of the plasma membrane pinches off a

small volume of extracellular fluid

� Used by intestinal cells to sample the environment


Receptor Mediated Endocytosis

Figure 3.13c

-Very selective

-Receptors are plasma membrane proteins

-Receptors and bound substrate are internalized

-Used to internalize enzymes, insulin, hormones, etc…


Passive Membrane Transport – Review

Formation of kidney filtrateHydrostatic pressureFiltration

Movement of H2O in & out of cellsKinetic energyOsmosis

Movement of glucose into cellsKinetic energyFacilitated diffusion

Movement of O2 through membraneKinetic energySimple diffusion

ExampleEnergy SourceProcess


Active Membrane Transport – Review

Intracellular trafficking of

moleculesATP

Endocytosis via coatomer

vesicles

Cholesterol regulationATPEndocytosis via caveoli

Hormone and cholesterol uptakeATPReceptor-mediated endocytosis

Absorption by intestinal cellsATPFluid-phase endocytosis

White blood cell phagocytosisATPEndocytosis

Neurotransmitter secretionATPExocytosis

Movement of ions across

membranesATPActive transport of solutes

ExampleEnergy SourceProcess


Membrane Potential

� Voltage across a membrane

� Voltage is “Electrical” potential energy resulting

from the separation of oppositely charged particles

� In cells, ions (K+ and Na+) are the charged particles

and the plasma membrane keeps them separated


Membrane Potential

� Resting membrane potential – the point where K+

potential is balanced by the membrane potential

� Ranges from –20 to –200 mV

� Results from Na+ and K+ concentration gradients across the membrane

� Differential permeability of the plasma membrane to Na+ and K+

� Steady state – potential maintained by active transport of ions


Generation and Maintenance of Membrane Potential

Figure 3.15


Membrane Potential

� Na+ also influences the resting membrane potential

� Na+ is strongly attracted to the negatively charged

cell interior and by the sodium ion’s concentration

gradient bringing the resting membrane potential

to -70mV


Membrane Potential

� However, the membrane is much more

permeable to K+ than it is to Na+

� If passive forces only were at work, the [K+] and

[Na+] would eventually become equal inside and

outside

� Active transport maintains the ionic imbalance and

thus the membrane potential as well as the osmotic

balance!


Cell Environment Interactions:Cell Adhesion Molecules (CAMs)

� Involved in embryonic development, wound repair, immunity

� E.g. cadherins, integrins

� Anchor cells to each other & the extracellular matrix

� Assist in movement of cells past one another

� Rally protective white blood cells to injured or infected areas

� Mechano-receptor- stimulating synthesis or degradation of adhesive membrane junctions

� Involved in intracellular signaling that directs migration, proliferation, specialization during development


Roles of Membrane Receptors

� Contact signaling – touching of cells

� Electrical signaling – voltage-regulated “ion gates”in nerve and muscle tissue respond to changes in membrane potential

� Chemical signaling – neurotransmitters bind to chemically gated channel-linked receptors in nerve and muscle tissue

� G protein-linked receptors – ligands bind to a receptor which activates a G protein, causing the release of a second messenger, such as cyclic AMP


Operation of a G Protein

� An extracellular ligand (first messenger), binds to a specific plasma membrane protein

� The receptor activates a G protein that relays the message to an effector protein

� The effector is an enzyme that produces a second messenger inside the cell

� The second messenger activates a kinase

� The activated kinase can trigger a variety of cellular responses


Operation of a G Protein

Figure 3.16

Extracellular fluid

Cytoplasm

Inactivesecondmessenger

Cascade of cellular responses(metabolic and structural changes)

Effector(e.g., enzyme)

Activated(phosphorylated)kinases

First messenger(ligand)

Activesecondmessenger(e.g., cyclicAMP)

Membranereceptor

G protein

1

2

3 4

5

6


Cytoplasm

� Cytoplasm – material between plasma membrane

and the nucleus

� Site where most cellular activities happen

� Consists of three major elements:

� Cytosol

� Organelles

� Inclusions


Cytoplasm

� Cytosol – viscous fluid that suspends the

organelles and inclusions and gives cell shape.

� Largely water with dissolved protein, salts, sugars,

and other solutes


Cytoplasm

� Cytoplasmic organelles – metabolic machinery of

the cell

� Inclusions – storage areas for nutrients such as

glycosomes, glycogen granules, and pigment


Cytoplasmic Organelles

� Specialized cellular compartments each performing a job

like the organs of the body

� Organelles are membranous and can maintain an isolated

environment often different than the cytoplasm and other

organelles

� Membranous

� E.g. Mitochondria, peroxisomes, lysosomes, endoplasmic

reticulum, and Golgi apparatus

� Nonmembranous

� E.g. Cytoskeleton, centrioles, and ribosomes


Mitochondria

� Double membrane structure with shelf-like cristae

� Provide most of the cell’s ATP via aerobic cellular respiration

� Located in sites where energy is needed

� Contain their own DNA and RNA and can reproduce

� Function: Intermediate products of food fuels (e.g. glucose) are broken down into water, CO2 while a phosphate is attached to ADP ATP


Mitochondria

Figure 3.17a, b

Outer membrane is smooth and featureless, while

the inner membrane folds inward forming cristae


Ribosomes

� Granules containing protein and rRNA

� Site of protein synthesis

� Free ribosomes synthesize soluble proteins that function in the cytosol

� Membrane-bound ribosomes synthesize proteins to be incorporated into membranes or export from the cell

-Free and Membrane bound ribosomes

can attach and detach according to need


Ribosomes


Endoplasmic Reticulum (ER)

� Membranous network surrounding the nucleus

� Continuous with the nuclear membrane

� Accounts for ½ of the cells membranes!

� Two varieties – rough ER and smooth ER


Endoplasmic Reticulum (ER)

Figure 3.18a, c


Rough (ER)

� External surface studded with ribosomes

� Manufactures all secreted proteins

� Responsible for the synthesis of integral membrane

proteins and phospholipids for cell membranes


Signal Mechanism of Protein Synthesis

� mRNA – ribosome complex is directed to rough

ER by a signal-recognition particle (SRP)

� SRP is released and polypeptide grows into

cisternae

� The protein is released into the cisternae and sugar

groups are added



� The protein folds into a three-dimensional

conformation

� The protein is enclosed in a transport vesicle and

moves toward the Golgi apparatus



Figure 3.19

Cytosol

Ribosomes

mRNA

Coatomer-coatedtransportvesicle

Transportvesiclebudding off

Releasedglycoprotein

ERcisterna

ERmembrane

Signal-recognitionparticle(SRP)

Signalsequence

Receptorsite

Sugargroup

SignalsequenceremovedGrowing

polypeptide

1

2

34

5


Smooth ER

� Plays no role in protein synthesis

� Catalyzes the following reactions in various organs of the

body

� In the liver – lipid and cholesterol metabolism, breakdown

of glycogen and, along with the kidneys, detoxification of

drugs

� In the testes – synthesis of steroid-based hormones

� In the intestinal cells – absorption, synthesis, and transport

of fats

� In skeletal and cardiac muscle – storage and release of

calcium


KU Game Day!!

chapter 3 part i - edl€¦ · copyright © 2006 pearson education, inc., ... inc., publishing as...

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