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5
Cell Signaling and
Communication
7.1 What Are Signals, and How Do Cells Respond to Them?
All cells process information from the
environment.
The information can be a chemical, or a
physical stimulus such as light.
Signals can come from outside the
organism, or from neighboring cells.
Not all cells can respond to all signals ! A
cell must have a specific receptor that
can detect a specific signal
7.1 What Are Signals, and How Do Cells Respond to Them?
In a large multicellular organism, signals
reach target cells by diffusion or by
circulation in the blood.
Autocrine signals affect the cells that
made them.
Paracrine signals affect nearby cells.
Hormones travel to distant cells, usually
via the circulatory system.
Figure 7.1 Chemical Signaling Systems
autocrine
paracrine
Hormone
7.1 What Are Signals, and How Do Cells Respond to Them?
To respond to a signal, a cell must have
a specific receptor that can detect it.
A signal transduction pathway is the
sequence of molecular events and
chemical reactions that lead to a cell’s
response to a signal.
=> Involves a signal, a receptor and a
response
Figure 7.2 A Signal signal
Transduction Pathway
receptor
response
Figure 7.5 Two Locations for Receptors
Figure 7.3 A Model Signal Transduction Pathway (Part 2)
The solute
concentration
around
Escherichia coli in
a mammalian
intestine changes
often.
The bacterium
must respond
quickly to this
environmental
signal.
Figure 7.3 A Model Signal Transduction Pathway (Part 2)
The solute
concentration
around E. coli in a
mammalian
intestine changes
often.
The bacterium
must respond
quickly to this
environmental
signal.
Figure 7.3 A Model Signal Transduction Pathway (Part 2)
The solute
concentration
around E. coli in a
mammalian
intestine changes
often.
The bacterium
must respond
quickly to this
environmental
signal.
7.1 What Are Signals, and How Do Cells Respond to Them?
Conformation of OmpR (the responder)
changes.
Signal from outside has now been
transduced to a protein inside the cell.
The effect: Phosphorylated OmpR binds
to DNA to increase the expression of
the protein OmpC.
Figure 7.3 A Model Signal Transduction Pathway (Part 2)
The solute
concentration
around E. coli in a
mammalian
intestine changes
often.
The bacterium
must respond
quickly to this
environmental
signal.
7.1 What Are Signals, and How Do Cells Respond to Them?
The signal has been amplified: One EnvZ
molecule can change the conformation
of many OmpR molecules.
The OmpC protein is inserted in the outer
membrane where it blocks pores and
prevents solutes from entering.
7.1 What Are Signals, and How Do Cells Respond to Them?
Summary of this signal transduction pathway:
•  The signal causes a receptor protein to change
conformation
•  Conformation change gives it protein kinase activity
•  Phosphorylation alters function of a responder protein
•  The signal is amplified
•  A protein that binds to DNA is activated
•  Expression of one or more genes is turned on or off
•  Cell activity is altered
Figure 7.9 A Cytoplasmic Receptor
Cytoplasmic receptors
bind ligands that can
cross the plasma
membrane.
Binding to ligand causes
receptor to change shape
—allows it to enter
nucleus, where it affects
gene expression.
Receptor may be bound to
a chaperonin; binding to
ligand releases the
chaperonin.
7.5 How Do Cells Communicate Directly?
Multicellular organisms have cell junctions that allow
communication:
•  Gap junctions in animals
Gap junctions: Channels
between adjacent cells
traversed by proteins
forming a channel.
Too small for proteins, but
wide enough for signaling
molecules.
5
Energy, Enzymes, and
Metabolism
8.1 What Physical Principles Underlie Biological Energy
Transformations?
The transformation of energy is a
hallmark of life.
Energy is the capacity to do work, or the
capacity for change.
Energy transformations are linked to
chemical transformations in cells.
8.1 What Physical Principles Underlie Biological Energy
Transformations?
Metabolism: Sum total of all chemical
reactions in an organism.
Anabolic reactions: Complex molecules
are made from simple molecules; energy
input is required.
Catabolic reactions: Complex molecules
are broken down to simpler ones and
energy is released.
Figure 8.5 ATP (Part 1)
ATP is a nucleotide.
8.2 What Is the Role of ATP in Biochemical Energetics?
ATP is a nucleotide.
Hydrolysis of ATP yields free energy.
ATP + H 2O → ADP + Pi + free energy
Réaction exoénergétique
Figure 8.5 ATP (Part 2)
8.2 What Is the Role of ATP in Biochemical Energetics?
Bioluminescence is an endergonic
reaction driven by ATP hydrolysis:
luciferase
luciferin + O2 + ATP ⎯⎯⎯
⎯→
oxyluciferin + AMP + PPi + light
8.2 What Is the Role of ATP in Biochemical Energetics?
The formation of ATP is endergonic:
ADP + Pi + free energy → ATP + H 2O
Formation and hydrolysis of ATP couples
exergonic and endergonic reactions.
Figure 8.6 Coupling of Reactions
Exergonic and endergonic reactions are coupled.
Figure 8.6 Coupling of Reactions
Exergonic and endergonic reactions are coupled.
8.3 What Are Enzymes?
Catalysts speed up the rate of a reaction.
The catalyst is not altered by the
reactions.
Most biological catalysts are enzymes
(proteins) that act as a framework in
which reactions can take place.
8.3 What Are Enzymes?
Biological catalysts (enzymes and ribozymes) are
highly specific.
Reactants are called substrates.Substrate
molecules bind to the active site of the enzyme.
The three-dimensional shape of the enzyme
determines the specificity.
5
Pathways that Harvest
Chemical Energy
9.1 How Does Glucose Oxidation Release Chemical Energy?
Fuels: Molecules whose stored energy
can be released for use.
The most common fuel in organisms is
glucose. Other molecules are first
converted into glucose or other
intermediate compounds.
9.1 How Does Glucose Oxidation Release Chemical Energy?
•  Three metabolic pathways are involved in
harvesting the energy of glucose:
•  Glycolysis—glucose is converted to
pyruvate
•  Cellular respiration—aerobic and
converts pyruvate into H2O, CO2, and ATP
•  Fermentation—anaerobic and converts
pyruvate into lactic acid or ethanol, CO2,
and ATP
Figure 9.1 Energy for Life
9.1 How Does Glucose Oxidation Release Chemical Energy?
If O2 is present (aerobic) glycolysis is followed
by three pathways of cellular respiration:
•  Pyruvate oxidation
•  Citric acid cycle (= Krebs cycle)
•  Electron transport chain
If O2 is not present, pyruvate from glycolysis is
metabolized by fermentation.
Figure 9.4 Energy-Producing Metabolic Pathways
Table 9.1
The five metabolic pathways occur in different
parts of the cell.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Glycolysis takes place in the cytosol:
• Converts glucose into pyruvate
• Produces a small amount of energy
• Generates no CO2
Results in: 2 molecules of pyruvate
2 molecules of ATP
10 steps (reactions) with 10 enzymes
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 1)
Glycolysis
http://theses.ulaval.ca/archimede/fichiers/23727/23727_4.png
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Pyruvate Oxidation:
•  Links glycolysis and the citric acid cycle; occurs in the
mitochondrie
•  Pyruvate is oxidized to acetate and CO2 is released
•  Some energy is stored by combining acetate and
Coenzyme A (CoA) to form acetyl CoA
Figure 9.7 Pyruvate Oxidation and the Citric Acid Cycle (Part 1)
Figure 9.7 Pyruvate Oxidation and the Citric Acid Cycle (Part 2)
Figure 9.6 Changes in Free Energy During Glycolysis and the
Citric Acid Cycle
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
The electron carriers that are reduced
during the citric acid cycle must be
reoxidized to take part in the cycle again.
Fermentation—if no O2 is present
Oxidative phosphorylation—O2 is present
Figure 9.9 The Respiratory Chain and ATP Synthase Produce
ATP by a Chemiosmotic Mechanism (Part 1)
Figure 9.9 The Respiratory Chain and ATP Synthase Produce
ATP by a Chemiosmotic Mechanism (Part 2)
9.3 How Does Oxidative Phosphorylation Form ATP?
Oxidative phosphorylation: ATP is
synthesized by reoxidation of electron
carriers in the presence of O2.
Two stages:
• Electron transport
• Transport protons across membrane
Figure 9.13 Cellular Respiration Yields More Energy Than
Fermentation
Cellular respiration yields
more energy than
fermentation per
glucose molecule.
•  Glycolysis plus
fermentation = 2 ATP
•  Glycolysis plus cellular
respiration = 32 ATP
Figure 9.14 Relationships among the Major Metabolic Pathways
of the Cell
9.1 How Does Glucose Oxidation Release Chemical Energy?
Principles governing metabolic pathways:
• Complex chemical transformations occur in
a series of reactions
• Each reaction is catalyzed by a specific
enzyme
• Metabolic pathways are similar in all
organisms
• In eukaryotes, metabolic pathways are
compartmentalized in organelles
• Each pathway is regulated by key enzymes
8.5 How Are Enzyme Activities Regulated?
Metabolic
pathways can
be modeled
using
mathematical
algorithms.
This field is
called
systems
biology.
Figure 9.15 Regulation by Negative and Positive Feedback
5
The Cell Cycle and Cell
Division
11.1 How Do Prokaryotic and Eukaryotic Cells Divide?
The life cycle of an organism is linked to cell division.
Unicellular organisms use cell division primarily for
reproduction.
In multicellular organisms, cell division is also
important in growth and repair of tissues.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide?
Four events must occur for cell division:
• Reproductive signal: To initiate cell
division
• Replication: Of DNA
• Segregation: Distribution of the DNA
into the two new cells
• Cytokinesis: Separation of the two
new cells
11.1 How Do Prokaryotic and Eukaryotic Cells Divide?
In prokaryotes, binary fission results in
two new cells.
External factors such as nutrient
concentration and environmental
conditions are the reproductive signals
that initiate cell division.
For many bacteria, abundant food
supplies speed up the division cycle.
Figure 11.2 Prokaryotic Cell Division (Part 1)
11.1 How Do Prokaryotic and Eukaryotic Cells Divide?
In eukaryotes, signals for cell division are
related to the needs of the entire organism.
• Growth factors: External chemical signals
that stimulate these cells to divide
• Platelet-derived growth factor: From
platelets that initiate blood clotting,
stimulates skin cells to divide and heal
wounds.
11.1 How Do Prokaryotic and Eukaryotic Cells Divide?
DNA replication usually occurs between cell divisions.
Sister chromatids—newly replicated chromosomes are
closely associated. (many chromosomes !)
Mitosis separates them into two new nuclei, identical to
the parent cell.
Meiosis is nuclear division in cells involved in sexual
reproduction.
The cells resulting from meiosis are not identical to the
parent cells.
11.2 How Is Eukaryotic Cell Division Controlled?
The cell cycle: The
period between cell
divisions, divided
into mitosis/
cytokinesis and
interphase.
Interphase: The cell
nucleus is visible
and cell functions
including replication
occur.
Interphase begins
after cytokinesis and
ends when mitosis
starts.
11.2 How Is Eukaryotic Cell Division Controlled?
Interphase has three subphases: G1, S, and G2
•  G1: Gap 1—between end of cytokinesis and
onset of S phase; chromosomes are single,
unreplicated structures
•  S phase: DNA replicates; one chromosome
becomes two sister chromatids
•  G2: Gap 2—end of S phase, cell prepares for
mitosis
Figure 11.8 Chromosomes, Chromatids, and Chromatin
11.3 What Happens during Mitosis?
After DNA replicates, its segregation occurs during
mitosis.
http://commons.wikimedia.org/wiki/File:%C3%89v%C3%A9nements_importants_en_mitose.svg
11.3 What Happens during Mitosis?
Mitosis can be divided into phases:
•  Prophase
•  Prometaphase
•  Metaphase
•  Anaphase
•  Telophase
11.3 What Happens during Mitosis?
Cytokinesis: Division of the cytoplasm
differs in plant and animals.
Mitosis ensures precise distribution of
chromosomes
The organelles are not necessarily
equally distributed
11.4 What Role Does Cell Division Play in a Sexual Life Cycle?
Somatic cells—body cells not
specialized for reproduction.
Each somatic cell contains
homologous pairs of chromosomes
with corresponding genes. Each parent
contributes one homolog.
11.4 What Role Does Cell Division Play in a Sexual Life Cycle?
Sexual reproduction: The offspring are
not identical to the parents.
It requires gametes created by meiosis;
two parents each contribute one
gamete to an offspring.
Gametes—and offspring—differ
genetically from each other and from
the parents.
11.4 What Role Does Cell Division Play in a Sexual Life Cycle?
Gametes contain only one set of chromosomes.
•  Haploid: Number of chromosomes = n
•  Fertilization: Two haploid gametes (female egg and
male sperm) fuse to form a diploid zygote;
chromosome number = 2n
Sexual reproduction generates diversity among
individual organisms.
Figure 11.15 Fertilization and Meiosis Alternate in Sexual
Reproduction (Part 3)
11.5 What Happens during Meiosis?
Meiosis consists of two nuclear divisions but DNA is
replicated only once. The function of meiosis is to:
•  Reduce the chromosome number from diploid to
haploid
•  Ensure that each haploid has a complete set of
chromosomes
•  Generate diversity among the products
11.5 What Happens during Meiosis?
11.5 What Happens during Meiosis?
Differences between meiosis II and mitosis:
• DNA does not replicate before meiosis II
• In meiosis II the sister chromatids may not
be identical because of crossing over
Figure 11.21 Nondisjunction Leads to Aneuploidy
11.5 What Happens during Meiosis?
In humans, if both chromosome 21 homologs go to the
same pole and the resulting egg is fertilized, it will be
trisomic for chromosome 21.
This results in the condition known as Down syndrome.
A fertilized egg that did not receive a copy of chromosome
21 will be monosomic, which is lethal.
11.6 In a Living Organism, How Do Cells Die?
Cell death occurs in two ways:
• Necrosis—cell is damaged or starved
for oxygen or nutrients. The cell swells
and bursts
Cell contents are released to the
extracellular environment and can cause
inflammation
11.6 In a Living Organism, How Do Cells Die?
•  Apoptosis is genetically programmed cell
death. Two possible reasons:
Cell is no longer needed, e.g., the connective
tissue between the fingers of a fetus
Old cells may be prone to genetic damage
that can lead to cancer; blood cells and
epithelial cells die after days or weeks
11.7 How Does Unregulated Cell Division Lead to Cancer?
Cancer cells differ from original cells in
two ways:
• Cancer cells lose control over cell
division
• They can migrate to other parts of the
body
11.7 How Does Unregulated Cell Division Lead to Cancer?
Normal cells divide in response to extracellular
signals, like growth factors.
Cancer cells don’t respond to these signals, instead
growing almost continuously.
A tumor is a large mass of cells.
Benign tumors resemble the tissue they grow from,
grow slowly, and remain localized.
Malignant tumors do not resemble the tissue they
grow from and may have irregular structures.
11.7 How Does Unregulated Cell Division Lead to Cancer?
Oncogene proteins are positive regulators of cancer
cells.
Derived from normal regulators that are overactive or
in excess, such as growth factors or their receptors.
Example: An increased number of receptors for HER2
in breast tissue may result in rapid cell proliferation.
11.7 How Does Unregulated Cell Division Lead to Cancer?
Tumor suppressors are negative regulators in both
cancer and normal cells, but in cancer cells they are
inactive.
Proteins such as p21, p53, and RB that normally
block the cell cycle are tumor suppressors but may
be blocked by a virus, such as HPV.
http://missinglink.ucsf.edu/lm/cell_cycle/oncogenes.html