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Cells: The Living Units
Why?
• What are some major issues in health?
• Most will come down to cellular issues.
Cell Theory
1. The cell is the basic structural
and functional unit of life
2. Organismal activity depends on
individual and collective activity
of cells
3. Biochemical activities of cells are
dictated by subcellular structure
4. Continuity of life has a cellular basis
Cell Theory
1. Cells are the building blocks of
life
•
Cells are the smallest unit of life
2. Each cell has its own job but
cells also work together to do a bigger
job.
3. A cells is the sum of its parts. And it has
a lot of parts.
4. All cells come from other cells.
Cell Theory
1. Cells are the building blocks of
life
•
Cells are the smallest unit of life
2. Each cell has its own job but
cells also work together to do a bigger
job.
3. A cells is the sum of its parts. And it has
a lot of parts.
4. All cells come from other cells.
Cell types
Epithelial Cell
Red Blood Cell
Neuronal Cell
Macrophage
Structure of a Generalized Cell
Cells (and factories) need…
Security/walls……………….
Communication with the
outside……………………
Power supply…………….…
Blue Prints………………….
Spare parts………….………
Plasma membrane
Internal transportation…...…
Assembly line and QC…..…
Ability to export……………..
Microtubules
Membrane receptors
ATP
DNA, RNA
amino acids, lipids, nucleotides,
sugars
ER, Golgi
Exocytosis (vesicles)
Animal Cell Components
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Plasma membrane
Nucleus
Ribosomes
Endoplasmic
reticulum
Golgi body
Vesicles
Mitochondria
Cytoskeleton
Model of the Plasma Membrane
Plasma Membrane
We are going to describe
what plasma membranes
do by breaking things into
5 major functions:
1.
2.
3.
4.
5.
Forms a barrier
Controls exit and entry
Maintains a voltage
Cell to cell communication
Support
PM Forms a barrier
The Barrier is Provided
by a Lipid Bilayer
• Made of phospholipids
• Gives membrane its fluid properties
• Two layers of phospholipids
– Hydrophilic heads face outward
– Hydrophobic tails in center
Barrier
The Lipid Bilayer
Barrier
The PM is very fluid
Barrier
The Plasma Membrane
is the Gatekeeper
• Larger molecules must be let in
by a specific mechanism; a pump or
channel.
• Small molecules may pass through the
plasma membrane by diffusion.
Barrier
Diffusion
•Diffusion is basically
that things do not like to
be next to each other, so
they move apart.
Barrier
Diffusion
• Diffusion is important in biology
because when salts move, they
take water with them. This is
called osmosis.
• CF: In CF, patients cannot move
salt, which prevents them from
being able to move water. Thus
mucous cannot be
diluted and their
lungs fill with mucous.
• Cholera toxin
• Cell swelling and
shrinking
Barrier
Osmosis
• Diffusion of water across a membrane (in
our case the plasma membrane)
– Basically, if things can move apart they will by
diffusion.
– If things cannot move apart because they are
held in by the PM, they will try to draw water
into the cell to help move apart.
• The likelihood of osmosis is dependent on
the tonicity of the solution.
Barrier
Tonicity
Refers to the solution outside
of the cell relative to the
solution inside.
• 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
Barrier
Isotonic
Hypotonic
Hypertonic
Osmosis
in RBCs
Barrier
The Plasma Membrane
Controls Entry into the Cell
• At this point, we have talked about how
the plasma membrane is a barrier to most
things.
• Some things have to be let inside and out
of the cell and this is regulated by
membrane proteins.
Exit and entry
Membrane
Proteins
Just say, wow
there are a lot of
different
membrane
proteins and we
are good for
now….
Exit and entry
Membrane Proteins
We Will Look at More
Closely
• Intercellular joining
• Transport
• Receptors for signal
transduction
Exit and entry
Intercellular Joining
• 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
Exitexit
andand
entry
PM controls
entry with membrane proteins
Membrane Junctions: Tight
Junction
Exitexit
andand
entry
PM controls
entry with membrane proteins
Membrane
Junctions:
Gap
Junction
Exitexit
andand
entry
PM controls
entry with membrane proteins
Membrane Transport
There are 3 main types of transport;
passive, active and bulk flow
1.
2.
3.
Passive transport requires no
energy source and is for moving
small molecules across the PM
Active transport also moves small
molecules but requires ATP
Bulk flow occurs when large
pieces of membrane,
and their contents,
are moved.
Exitexit
andand
entry
PM controls
entry with membrane proteins
Transport
Passive
Simple
Diffusion
Facilitated
Diffusion
Direction
Symport
Exit and entry
Active
No energy
Antiport
Requires energy
ATP use
Primary
Secondary
Passive Membrane Transport:
Diffusion
• Simple diffusion – nonpolar and lipidsoluble substances
–Diffuse directly through the lipid
bilayer
Exit and entry
Passive Membrane Transport:
Diffusion
• Facilitated diffusion
–Transport of glucose, amino acids,
and ions
–Transported
substances bind
carrier proteins
or pass through
protein channels
Exit and entry
Diffusion Through the Plasma
Membrane
Exit and entry
Active Transport
• Uses ATP to move solutes across a
membrane
• Requires carrier proteins
Exit and entry
Types of Active Transport:
Direction of 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
Exit and entry
Antiporters and Symporters
Exit and entry
Types of Active Transport:
Use of ATP
• Primary active transport –
hydrolysis of ATP phosphorylates
the transport protein causing
conformational change
• Secondary active transport – use
of an exchange pump (such as
the Na+-K+ pump) indirectly to
drive the transport of other
solutes
Exit and entry
Types of Bulk Transport
• Transport of large particles and
macromolecules across plasma
membranes
– Exocytosis
Exocytosis
– moves out
– Endocytosis
– moves in
Endocytosis
Exit and entry
Vesicular Transport
– Transcytosis – moving substances into,
across, and then out of a cell
– Vesicular trafficking – moving substances
from one area in the cell to another
– Phagocytosis – pseudopods engulf solids and
bring them into the cell’s interior
Exit and entry
Vesicular Transport
• Fluid-phase endocytosis – the plasma
membrane infolds, bringing extracellular
fluid and solutes into the interior of the cell
• Receptor-mediated endocytosis – clathrincoated pits provide the main route for
endocytosis and transcytosis
• Non-clathrin-coated vesicles – caveolae
that are platforms for a variety of signaling
molecules
Exit and entry
The PM also Maintains a
Membrane Potential
• The PM separates Na+ and K+ such that a
voltage is developed.
• The Na+ and K+ are separated
via the Na+ /K+ ATPase.
• The purpose of this voltage
is to:
– Provide a basis for electrical
signaling
– Provide a gradient for active
transport
voltage
Na/K ATPase
voltage
Na+/K+ Pump & ATP As Its Energy
Source
1. Na+ binding
4. K+ binding
2. ATP split
5. Phosphate
release
6. K+ is pushed in
3. Na+pushed out
3 Na+ ions removed from cell as 2 K+ brought into cell.
voltage
Cell to Cell Communication
• Cells need to talk their environment,
whether it is a neuron telling a muscle to
move or insulin telling cells to take up
glucose.
• This “talking” is done through membrane
receptors.
communication
Membrane Receptors:
Roles
• Contact signaling – important in
normal development and immunity
• Electrical signaling – voltage-regulated
“ion gates” in nerve and muscle tissue
• 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
communication
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
communication
Operation of a G
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
communication
Operation
of a
G Protein
communication
Cytoskeleton
• The “skeleton” of the cell
• Dynamic, elaborate series of rods running
through the cytosol
• Consists of microtubules, microfilaments,
and intermediate filaments
support
Cytoskeleton
support
Microfilaments
• Dynamic strands of the
protein actin
• Attached to the
cytoplasmic side of the
plasma membrane
• Braces and strengthens
the cell surface
• Function in endocytosis
and exocytosis
support
PM allows
support
Intermediate Filaments
• Tough, insoluble
protein fibers with high
tensile strength
• Resist pulling forces on
the cell and help form
desmosomes
support
Microtubules
• Dynamic, hollow tubes
made of the spherical
protein tubulin
• Determine the overall shape of the cell
and distribution of organelles
• Also, forms the basic structure of things
like cilia and flagella.
• The tracks on which things are moved
around in cells.
support
PM allows
support
Centrioles
• Small barrel-shaped
organelles located in the
centrosome near the
nucleus
• Pinwheel array of nine triplets of
microtubules
• Organize mitotic spindle during mitosis
• Form the bases of cilia and flagella
support
PM allows
support
Centrioles and Microtubules
Cilia
• Whiplike, motile cellular extensions on
exposed surfaces of certain cells
• Move substances in one direction across
cell surfaces
support
PM allows
support
Motor
Molecules
• Protein complexes
that function in
motility
• Powered by ATP
• Attach to receptors
on organelles
support
movie
That’s it for PM (for now)
Animal Cell Components
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Plasma membrane
Nucleus
Ribosomes
Endoplasmic
reticulum
Golgi body
Vesicles
Mitochondria
Cytoskeleton
Nucleus
• Gene-containing control
center of the cell
• Contains nuclear envelope,
nucleoli, and chromatin
• Contains the genetic library with blueprints
for nearly all cellular proteins
• Dictates the kinds and amounts of proteins
to be synthesized
Nucleus
Nucleoli
• Dark-staining spherical bodies within the
nucleus
• Site of ribosome production
Chromatin
• Threadlike strands
of DNA and histones
• Arranged units
called nucleosomes
• Form condensed,
barlike bodies of
chromosomes when
the nucleus starts to
divide
Nucleus and Chromatin
Nuclear Membrane
Nucleus
Nucleolus
Chromatin
Animal Cell Components
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Plasma membrane
Nucleus
Ribosomes
Endoplasmic
reticulum
Golgi body
Vesicles
Mitochondria
Cytoskeleton
Endomembrane System and
Organelles
• The rest of the inside of the cell can
be divided into two major systems.
– endomembrane system
– organelles
Endomembrane System
•
One of the main
functions of the
endomembrane
system is to make
proteins
–
•
It also does things
like digest fats,
toxins, etc.
Everything in us is
made basically of
protein.
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–
–
–
–
–
Structural proteins
Contractile proteins
Transport proteins
Enzymes
Buffering proteins
Antibodies
Endomembrane System
• System of organelles that function to:
– Produce, store, and export biological
molecules
• Make stuff
– Degrade potentially harmful substances
• Get rid of stuff
Endomembrane System
•
System includes:
1. Nuclear envelope
2. Smooth and rough
ER
3. Lysosomes
4. Vacuoles
5. Transport vesicles
6. Golgi apparatus
7. The plasma
membrane
1
2
3
2
4
5
7
6
Nuclear Envelope
• Selectively permeable double
membrane barrier containing
pores
• Encloses jellylike nucleoplasm, which contains
essential solutes
• Outer membrane is continuous with the rough
ER and is studded with ribosomes
• Pore complex regulates transport of large
molecules into and out of the nucleus
Endoplasmic Reticulum (ER)
• Interconnected tubes and parallel
membranes enclosing cisternae
• Continuous with the nuclear membrane
• Two varieties – smooth ER and rough ER
Smooth vs. Rough ER
Rough (ER)
• External surface studded
with ribosomes
• Manufactures all secreted
proteins
• Responsible for the
synthesis of integral
membrane proteins
Ribosomes
•
•
•
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Granules containing protein
and rRNA
Site of protein synthesis
Free ribosomes synthesize
soluble proteins in the
cytoplasm
Membrane-bound ribosomes
synthesize proteins
1. to be incorporated into membranes
2. or exocytosed.
5 steps of
protein sythesis:
they occur on
the surface of
the RER
5 Steps of RER Protein Synthesis
1.
2.
3.
4.
5.
mRNA – ribosome
complex is directed to
rough ER by a signalrecognition 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
5 Steps of RER
Protein Synthesis
1. mRNA – ribosome
complex is directed to
rough ER by a signalrecognition particle (SRP)
2. SRP is released and
polypeptide grows into
cisternae
3. The protein is released into
the cisternae and sugar
groups are added
5 Steps of RER
Protein
Synthesis
4. The protein folds into
a three-dimensional
conformation
5. The protein is
enclosed in a
transport vesicle and
moves toward the
Golgi apparatus
Close-up
of 5 steps
Smooth ER
• In all cells, SER is involved in lipid
metabolism.
• Also, SER does different things in
different places (cells)
– 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
Smooth ER
• Know:
–Smooth ER is mainly responsible
for fat and lipid metabolism.
–In muscle, SER is specialized to
release Ca2+ which leads to muscle
contraction.
–Detoxification of drugs in liver and
kidneys.
Golgi Apparatus
• Stacked and flattened
membranous sacs
• The “traffic director”
for cellular proteins
• Functions in modification,
concentration, and
packaging of proteins
made in the ER
Golgi Apparatus
Role of the Golgi Apparatus
Role of the Golgi Apparatus
1. Makes polysaccharides
2. Adds sugars to proteins which further
specializes a protein for function called
glycosylation
–
May serve signaling
– Cell fate
determination.
– Adds charge to
• 3. Quality Control
functions
proteins
Review
RER
Synthesis of
export
proteins
Synthesis of
membrane
boundproteins
SER
Fats
Golgi
Protein
modification
Detox
Concentration
Muscle
Contraction
Quality control
Sugars
Cytoplasmic Organelles
• Specialized cellular compartments
• Membranous: surrounded by a membrane
– Mitochondria, peroxisomes, lysosomes,
endoplasmic reticulum, and Golgi apparatus
• Nonmembranous
– Cytoskeleton,
centrioles, and
ribosomes
Lysosomes
Lysosomes
• Spherical membranous
bags containing digestive
enzymes
• Digest ingested bacteria, viruses, and
toxins
• pH of 5 due to acid hydrolases
• Degrade nonfunctional organelles
• Breakdown glycogen and release
thyroid hormone
Peroxisomes
• Not well understood
but interestingly use
about as much
oxygen as
mitochondria
• Detoxify harmful or toxic substances
• Neutralize dangerous free radicals
– Free radicals – highly reactive chemicals with
unpaired electrons (i.e., O2–)
Mitochondria
• Double membrane
structure with shelflike
cristae
• Provide most of the
cell’s ATP via aerobic
cellular respiration
• Contain their own DNA
and RNA
Cellular Respiration
Mitochondria
are basically
why you
breathe.
Mitochondria
use oxygen to
convert
glucose into
ATP.
Cytoplasm
• Cytoplasm – material
between plasma
membrane and the
nucleus
– Term for everything, fluid,
organelles, structures, etc.
• Cytosol – largely water
with dissolved protein,
salts, sugars, and other
solutes
– Fluid bath in the cell
Cell Cycle
Two Types of Cell Division
• Mitosis (somatic cell
division)
– one parent cell gives rise to
2 identical daughter cells
– occurs in billions of cells
each day
– needed for tissue repair and
growth
• Meiosis (reproductive cell
division)
– egg and sperm cell
production
– in testes and ovary only
Somatic Cell
Division
• Essential for body growth
and tissue repair
• Mitosis – nuclear division
• Cytokinesis – division of the
cytoplasm
Cell Cycle
• Interphase
– Growth
(G1),
synthesis
(S), growth
(G2)
• Mitotic
phase
– Mitosis and
cytokinesis
Interphase
• G1 (gap 1) – metabolic activity and
vigorous growth
• G0 – cells that permanently cease dividing
• S (synthetic) – DNA replication
• G2 (gap 2) – preparation for division
Mitosis
• The phases of mitosis are:
– Prophase
– Metaphase
– Anaphase
– Telophase
• I Passed My Anatomy Test
• IPMAT
To differentiate the stages:
Watch the centromeres
• Random: Prophase
• Lined up:
Metaphase
• In between the
“equator” and the
“poles” and the
chromosomes look
like little A’s:
Anaphase
• At the poles:
Telophase
Early Prophase
• Asters are seen as
chromatin
condenses into
chromosomes
• Nucleoli disappear
• Centriole pairs
separate and the
mitotic spindle is
formed
Early mitotic
spindle
Pair of
centrioles
Centromere
Aster
Chromosome, consisting
of two sister chromatids
Early prophase
Late
Prophase
• Centriole pairs
separate and the
mitotic spindle is
formed
Metaphase
• Chromosomes cluster at
the middle of the cell with
their centromeres aligned at
the exact center, or
equator, of the cell
• This arrangement of
chromosomes along a
plane midway between the
poles is called the
metaphase plate
– If you remember the term
metaphase plate, you will
remember what metaphase
is.
Metaphase plate
Spindle
Metaphase
Anaphase
• Centromeres of the chromosomes split
• Motor proteins in kinetochores pull
chromosomes toward poles
Anaphase
• Centromeres of the
chromosomes split
• Motor proteins in
kinetochores pull
chromosomes toward
poles
Daughter
chromosomes
Anaphase
Telophase
and
Cytokinesis
• New sets of chromosomes
extend into chromatin
• New nuclear membrane is
formed from the rough ER
• Nucleoli reappear
• A cleavage furrow formed
in late anaphase by
contractile ring
• Cytoplasm is pinched into
two parts after mitosis
ends
Review of IPMAT
•
•
•
•
Prophase
Metaphase
Anaphase
Telophase
Control of Cell Division: Cyclins
• Improper Cyclin Function = Cancer
• Cyclins stop division in certain situations
– Contact inhibition
– Damaged DNA p53
– Are the cells mature enough to be dividing.
• Cyclins work on the process of “stop, don’t
go” instead of “go, don’t stop.”
– An elegant example of biological sensitivity
http://nobelprize.org/medicine/educational/index.html
Control of Cell Division
Control of Cell Division
Control of Cell Division
Rb gene stops cell division
And is missing in many
forms of common cancer
(lung, breast, bladder)
Missing or less-potent p53
is associate with uv-induced
cancer.
DNA Replication
• Remember that the
two main functions of
DNA is to replicate
itself and to serve as
a blueprint for making
proteins.
• We will now go over
DNA replication.
• DNA replication is a
prelude to cell division
The first step
in DNA
replication:
Unwind
(done by
the enzyme
helicase)
DNA Replication
• DNA polymerase
works in only one
direction (5’ to 3’):
– A continuous leading
strand is synthesized
– A discontinuous lagging
strand is synthesized
– DNA ligase splices
together the short
segments of the
discontinuous strand
DNA Replication
• DNA polymerase
works in only one
direction (5’ to 3’): :
– One strand proceeds
easily 5 to 3
– The other strand must
go a small ways, and
then start again. This
creates what are called
Okazaki fragments.
5’ to 3’
Okazaki Fragments
• DNA
polymerase
• Okazaki
• 5 to 3
• Ligase
• Movie
Movie
• ..\..\..\My
Pictures\Movies\DNAreptrantrans\DNAReplicati
on.mov
Protein Synthesis
• DNA also serves as master blueprint for
protein synthesis
• Genes are segments of DNA carrying
instructions for a polypeptide chain
• Triplets of nucleotide bases form the
genetic library
• Each triplet specifies coding for an amino
acid
Protein Synthesis Overview
• Instructions for making specific
proteins is found in the DNA
(your genes)
– Transcribe that information onto a
messenger RNA molecule
• each sequence of 3 nucleotides in DNA
is called base triplet
• each base triplet is transcribed as 3 RNA
nucleotides (codon)
– Translate the “message” into a
sequence of amino acids in order
to build a protein molecule
• each codon must be matched by an anticodon found on the
tRNA carrying a specific amino acid
From DNA to Protein
Transcription
Transcription
• Transfer of information from
the sense strand of DNA to
RNA
• RNA polymerase:
– Unwinds the DNA template
– Adds complementary
ribonucleoside triphosphates
on the DNA template
– Joins these RNA nucleotides
together
– Encodes a termination signal
to stop transcription
Movie
• ..\..\..\My
Pictures\Movies\DNAreptrantrans\transcrip
tionlem6s5c.ram
Translation
Roles of the
Three Types of
RNA
• Messenger RNA (mRNA)
carries the genetic
information from DNA
in the nucleus to the
ribosomes in the cytoplasm
• Transfer RNAs (tRNAs) bound to amino acids
base pair with the codons of mRNA at the
ribosome to begin the process of protein
synthesis
• Ribosomal RNA (rRNA) is a structural
component of ribosomes
Initiation of Translation
• A leader sequence on mRNA attaches to
the small subunit of the ribosome
• Methionine-charged initiator tRNA binds to
the small subunit
– Methionine is always the first amino acid.
• The large ribosomal unit now binds to this
complex forming a functional ribosome
Translation
Translation
Info Transfer from DNA to RNA
Figure 3.39
Genetic Code
• RNA codons
code for amino
acids according
to a genetic code
• Universal
• Degenerate
• Know start and
stops.
Movie
• E:\movies\DNAreptrantrans\translationlem
6s6d.ram
Mutations
• Mutations are, in general, of two types:
– Environmental
– Mistakes in replication, transcription and
translation.
Environmental
Mutations
• Environmental
mutations are, in
general, of two types:
– Modified bases
– Breaks in the
phosphate
backbone
Mistake Mutations
• There are several varieties. In general,
they result in…
– Point mutations
– Frameshift mutations
– Deletions
– Insertion
– Inversion
Point Mutations
• Original: The fat cat ate the wee rat.
• Point Mutation: The fat hat ate the wee rat.
Frameshift Mutations
• Original: The fat cat ate the wee rat.
• Frame Shift: The fat caa tet hew eer at.
Actually, a deletion
is when you lose a
lot of nucleotides
(but I could not find
a picture)
Deletion
• Original: The fat cat ate the wee rat.
• Deletion: The fat ate the wee rat.
Germ-line Vs. Somatic Mutations
• Germ cells include sperm and egg cells.
– Mutations in these cells cause inheritable
mutations.
• Somatic Mutations:
– Mutations in the cells of the body. These
mutations may cause damage or cancer, but
they are not inheritable.
To sum us thus far…
All DNA is grouped into 46 chromosomes
(23 pairs)
A chromosome is a collection of genes
A gene is a collection of triplets
A triplet is a DNA code for a
particular amino acid
Continued….
A triplet codes for a particular
amino acid
A chain of amino acids forms
a polypeptide
Polypeptides are combined
to form proteins
PCR
• Polymerase Chain Reaction
– movie
• The ability to replicate DNA in a test tube.
– DNA evidence
• ..\..\..\My
Pictures\Movies\DNAreptrantrans\pcrgem6s1g.
ram