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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
The Cell
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
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
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
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
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
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.
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Cell Theory
Cells are composed of three principle areas
(regions)
� Plasma Membrane
� Cytoplasm
� Nucleus
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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
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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
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Fluid Mosaic Model
The Lipids of the Bilayer
� Phospholipids have hydrophobic and hydrophilic
bipoles
� Glycolipids are lipids with bound
carbohydrate
� Cholesterol
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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!!
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Fluid Mosaic Model
Figure 3.3
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Functions of Membrane Proteins
� Transport
� Enzymatic activity
� Receptors for signal
transduction
Figure 3.4.1
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Functions of Membrane Proteins
� Intercellular adhesion
� Cell-cell recognition
� Attachment to
cytoskeleton and
extracellular matrix
Figure 3.4.2
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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
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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
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Membrane Proteins
� Two types: Integral & Peripheral
� Integral: Span the lipid bilayer
They often are transmembrane proteins and
protrude on both sides of the membrane
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Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Peripheral Proteins
� Not embedded in the lipid bilayer
� Attach to integral proteins or membrane lipids
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Glycoproteins
� Proteins supporting sugar groups
� Includes many of the integral proteins that extend
into the extracellular space
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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
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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
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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
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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
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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
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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
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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
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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
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Passive Membrane Transport: 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
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Passive Membrane Transport: Diffusion
� 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
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Passive Membrane Transport: Diffusion
� 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
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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
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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
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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
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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
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Effect of Membrane Permeability on Diffusion and Osmosis
Figure 3.8a
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Effect of Membrane Permeability on Diffusion and Osmosis
Figure 3.8b
�[solute] must be equal on both sides of membrane
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Effect of Membrane Permeability on Diffusion and Osmosis
� 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
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Effect of Membrane Permeability on Diffusion and Osmosis
� Tonicity: the ability of a solution to change the
shape, or tone, of a cell by altering its internal
water volume
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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
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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
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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
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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
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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+
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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
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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
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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.
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Types of Active Transport
Figure 3.11
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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
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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
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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
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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
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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
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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)
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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
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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
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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…
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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
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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
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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
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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
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Generation and Maintenance of Membrane Potential
Figure 3.15
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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
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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!
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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
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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
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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
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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
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Cytoplasm
� Cytoplasm – material between plasma membrane
and the nucleus
� Site where most cellular activities happen
� Consists of three major elements:
� Cytosol
� Organelles
� Inclusions
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Cytoplasm
� Cytosol – viscous fluid that suspends the
organelles and inclusions and gives cell shape.
� Largely water with dissolved protein, salts, sugars,
and other solutes
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Cytoplasm
� Cytoplasmic organelles – metabolic machinery of
the cell
� Inclusions – storage areas for nutrients such as
glycosomes, glycogen granules, and pigment
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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
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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
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Mitochondria
Figure 3.17a, b
Outer membrane is smooth and featureless, while
the inner membrane folds inward forming cristae
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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
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Ribosomes
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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
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Endoplasmic Reticulum (ER)
Figure 3.18a, c
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Rough (ER)
� External surface studded with ribosomes
� Manufactures all secreted proteins
� Responsible for the synthesis of integral membrane
proteins and phospholipids for cell membranes
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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
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Signal Mechanism of Protein Synthesis
� The protein folds into a three-dimensional
conformation
� The protein is enclosed in a transport vesicle and
moves toward the Golgi apparatus
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Signal Mechanism of Protein Synthesis
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
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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
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KU Game Day!!
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