Respira,on 2/28/12
Cellular &
Photosynthesis:
Harves,ng Chemical Energy
Chapter 9 & 10
Life Is Work !
Living cells require energy from outside sources
Some animals, such as the chimpanzee, obtain
energy by ea,ng plants, and some animals feed on
other organisms that eat plants
Energy ows into an ecosystem as sunlight and
leaves as heat
Photosynthesis generates O2 and organic
molecules, which are used in cellular respira,on
Cells use chemical energy stored in organic
molecules to regenerate ATP, which powers work
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Light
energy
ECOSYSTEM
Photosynthesis
in chloroplasts
CO2 + H2O
Cellular respiration
in mitochondria
ATP
Organic
+ O2
molecules
ATP powers
most cellular work
Heat
energy
The transfer of electrons during chemical reactions releases energy stored in organic
molecules
Catabolic pathways yield energy by
oxidizing organic fuels
The breakdown of organic molecules is exergonic
Fermenta(on is a par,al degrada,on of sugars that occurs
without O2
Aerobic respira(on consumes organic molecules and O2
and yields ATP
Cellular respira(on includes both aerobic and anaerobic
respira,on but is oQen used to refer to aerobic respira,on
Although carbohydrates, fats, and proteins are all
consumed as fuel, it is helpful to trace cellular respira,on
with the sugar glucose
C6H12O6 + 6 O2 6 CO2 + 6 H2O + Energy (ATP + heat)
The Principle of Redox
Chemical reac,ons that transfer electrons between
reactants are called redox reac(ons
In oxida(on, a substance loses electrons, or is oxidized
In reduc(on, a substance gains electrons, or is reduced
becomes oxidized
(loses electron)
becomes reduced
(gains electron)
The electron donor is called the reducing agent
The electron receptor is called the oxidizing agent
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Oxida3on of Organic Fuel Molecules
During Cellular Respira3on
Products
Reactants
becomes oxidized
Energy
becomes reduced
Methane
(reducing
agent)
Oxygen
(oxidizing
agent)
Carbon dioxide
Water
Oxida3on of Organic Fuel Molecules
During Cellular Respira3on
becomes oxidized
becomes reduced
Harves,ng of energy from glucose has three stages
Glycolysis (breaks down glucose into two molecules
of pyruvate)
The citric acid cycle (completes the breakdown of
glucose)
Oxida(ve phosphoryla(on (accounts for most of the
ATP synthesis)
Photosynthesis is the Process That
Feeds the Biosphere
Autotrophs sustain themselves without ea,ng anything
derived from other organisms
Autotrophs are the producers of the biosphere, producing
organic molecules from CO2 and other inorganic
molecules whereas Heterotrophs are the consumers
Almost all plants are photoautotrophs, using the energy of
sunlight to make organic molecules
Photosynthesis is the process that converts solar energy
into chemical energy
Directly or indirectly, photosynthesis nourishes almost the
en,re living world
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Photosynthesis occurs in plants, algae,
certain other protists, and some
prokaryotes
(b) Multicellular
alga
(a) Plants
(d) Cyanobacteria
(c) Unicellular
protists
40 m
10 m
(e) Purple sulfur
1 m
bacteria
Photosynthesis converts light energy
to the chemical energy of food
Chloroplasts are structurally similar to and likely
evolved from photosynthe,c bacteria
Leaves are the major loca,ons of photosynthesis
Their green color is from chlorophyll, the green
pigment within chloroplasts
Chloroplasts are found mainly in cells of the
mesophyll, the interior ,ssue of the leaf
Each mesophyll cell contains 3040 chloroplasts
Leaf cross section
Chloroplasts Vein
Mesophyll
Stomata
Chloroplast
Thylakoid
Stroma Granum Thylakoid
space
CO2 O2
Mesophyll
cell
Outer
membrane
Intermembrane
space
Inner
membrane
20 m
CO2 enters and O2 exits
the leaf through
microscopic pores
called stomata
The chlorophyll is in the
membranes of
thylakoids (connected
sacs in the chloroplast);
thylakoids may be
stacked in columns
called grana
Chloroplasts also
contain stroma, a dense
interior uid
1 m
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Photosynthesis is a complex series of reac,ons that
can be summarized as the following equa,on:
6 CO2 + 12 H2O + Light energy C6H12O6 + 6 O2 + 6 H2O
Reactants:
Products:
6 CO2
1 2 H 2O
6 H2O
C6H12O6
6 O2
Photosynthesis as a Redox Process
Photosynthesis reverses the direc,on of electron
ow compared to respira,on
Photosynthesis is a redox process in which H2O is
oxidized and CO2 is reduced
Photosynthesis is an endergonic process; the energy
boost is provided by light
becomes reduced
C6 H12 O6 + 6 O2
Energy + 6 CO2 + 6 H2O
becomes oxidized
Figure 10.6-1
H 2O
Stages of Photosynthesis
Light
NADP+
ADP
+ Pi
Light
Reactions
Chloroplast
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Figure 10.6-2
H 2O
Stages of Photosynthesis
Light
NADP+
ADP
+ Pi
Light
Reactions
ATP
NADPH
Chloroplast
O2
Figure 10.6-3
CO2
H 2O
Light
NADP+
ADP
+ Pi
Light
Reactions
Calvin
Cycle
ATP
NADPH
Chloroplast
O2
CO2
H 2O
Light
NADP+
ADP
+ Pi
Light
Reactions
Calvin
Cycle
ATP
NADPH
Chloroplast
O2
[CH2O]
(sugar)
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Figure 10.7
10-5 nm 10-3 nm
103 nm
1 nm
Gamma
X-rays
rays
UV
1m
(109 nm)
106 nm
Infrared
Microwaves
103 m
Radio
waves
Visible light
380
450
500
550
600
650
700
750 nm
Longer wavelength
Shorter wavelength
Higher energy
Lower energy
The Nature of Sunlight
Light is a form of electromagne,c energy, also called
electromagne,c radia,on
Wavelength is the distance between crests of waves
The electromagne(c spectrum is the en,re range of
electromagne,c energy, or radia,on
Visible light consists of wavelengths (including those
that drive photosynthesis) that produce colors we can
see
Light also behaves as though it consists of discrete
par,cles, called photons
Photosynthe,c Pigments: The Light
Receptors
Light
Reflected
light
Chloroplast
Absorbed
light
Granum
Transmitted
light
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Photosynthe,c Pigments: The Light
Receptors
Pigments are substances that absorb visible light
Dierent pigments absorb dierent wavelengths
Wavelengths that are not absorbed are reected or
transmi`ed
Leaves appear green because chlorophyll reects and
transmits green light
A spectrophotometer measures a pigments ability to
absorb various wavelengths
This machine sends light through pigments and
measures the frac,on of light transmi`ed at each
wavelength
TECHNIQUE
Refracting Chlorophyll Photoelectric
solution
tube
White prism
Galvanometer
light
(b) Action spectrum
Low transmittance
(high absorption):
Chlorophyll absorbs
most blue light.
Absorption of light by
chloroplast pigments
(a) Absorption
spectra
High transmittance
(low absorption):
Chlorophyll absorbs
very little green light.
Rate of photosynthesis
(measured by O2 release)
RESULTS
Green
light
Blue
light
Slit moves to
pass light
of selected
wavelength.
Chlorophyll a
Chlorophyll b
Carotenoids
400
500
600
Wavelength of light (nm)
400
500
600
700
700
Aerobic bacteria
Filament
of alga
(c) Engelmanns
experiment
400
500
600
700
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Photosynthe,c Pigments: The Light
Receptors
Chlorophyll a is the main photosynthe,c pigment
Accessory pigments, such as chlorophyll b, broaden
the spectrum used for photosynthesis
Accessory pigments called carotenoids absorb
excessive light that would damage chlorophyll
When a pigment absorbs light, it goes from a ground
state to an excited state, which is unstable
A Photosystem: A Reac,onCenter
Complex Associated with Light
Harves,ng Complexes
A photosystem consists of a reac(oncenter complex
(a type of protein complex) surrounded by light
harves,ng complexes
The lightharves(ng complexes (pigment molecules
bound to proteins) transfer the energy of photons to
the reac,on center
Figure 10.14-5
Ele
ctro
Primary
acceptor
2 H+
+
O2
1/
2
H 2O
e-
2
Primary
acceptor
4
n tr
ans
Pq
port
cha
in
e-
Cytochrome
complex
E
tr lec
ch ans tron
ai po
n rt
7
Fd
e-
e-
8
NADP+
reductase
3
Pc
ee-
NADP+
+ H+
NADPH
P700
5
P680
Light
1 Light
6
ATP
Pigment
molecules
Photosystem II
(PS II)
Photosystem I
(PS I)
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Figure 10.15
e-
e-
e-
e-
Mill
makes
ATP
NADPH
e-
Photo
n
e-
ePhoto
n
ATP
Photosystem II
Photosystem I
Cyclic Electron Flow
Cyclic electron ow uses only photosystem I and
produces ATP, but not NADPH
No oxygen is released
Cyclic electron ow generates surplus ATP, sa,sfying
the higher demand in the Calvin cycle
Cyclic Electron Flow
Primary
acceptor
Primary
acceptor
Fd
Fd
Pq
NADP+
reductase
Cytochrome
complex
NADP+
+ H+
NADPH
Pc
Photosystem I
Photosystem II
ATP
Cyclic electron ow uses only photosystem I and produces
ATP, but no oxygen is released
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Cyclic Electron Flow
Some organisms such as purple sulfur bacteria have
PS I but not PS II
Cyclic electron ow is thought to have evolved before
linear electron ow
Cyclic electron ow may protect cells from
lightinduced damage
A Comparison of Chemiosmosis in
Chloroplasts and Mitochondria
Chloroplasts and mitochondria generate ATP by
chemiosmosis, but use dierent sources of energy
Mitochondria transfer chemical energy from food to
ATP; chloroplasts transform light energy into the
chemical energy of ATP
In mitochondria, protons are pumped to the
intermembrane space and drive ATP synthesis as they
diuse back into the mitochondrial matrix
In chloroplasts, protons are pumped into the thylakoid
space and drive ATP synthesis as they diuse back into
the stroma
Figure 10.17
Chloroplast
Mitochondrion
CHLOROPLAST
STRUCTURE
MITOCHONDRION
STRUCTURE
H+
Intermembrane
space
Inner
membrane
Matrix
Diffusion
Electron
transport
chain
Thylakoid
membrane
ATP
synthase
Stroma
ADP + P i
Key
Higher [H+ ]
Lower [H+ ]
Thylakoid
space
H+
ATP
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The Calvin cycle uses the chemical
energy of ATP and NADPH to reduce
CO2 to sugar
The Calvin cycle, like the citric acid cycle,
regenerates its star,ng material aQer molecules
enter and leave the cycle
The cycle builds sugar from smaller molecules by
using ATP and the reducing power of electrons
carried by NADPH
The Calvin cycle uses the chemical
energy of ATP and NADPH to reduce
CO2 to sugar
Carbon enters the cycle as CO2 and leaves as a sugar
named glyceraldehyde 3phospate (G3P)
For net synthesis of 1 G3P, the cycle must take place
three ,mes, xing 3 molecules of CO2
The Calvin cycle has three phases
Carbon xa(on (catalyzed by rubisco)
Reduc(on
Regenera(on of the CO2 acceptor (RuBP)
Figure 10.19-3
Input
3
(Entering one
at a time)
CO2
Phase 1: Carbon fixation
Rubisco
3P
Short-lived
intermediate
P
6
P
3-Phosphoglycerate
P
3P
Ribulose bisphosphate
(RuBP)
6
ATP
6 ADP
3 ADP
3
Calvin
Cycle
6P
P
1,3-Bisphosphoglycerate
ATP
Phase 3:
Regeneration of
the CO2 acceptor
(RuBP)
6 NADPH
6 NADP+
6 Pi
P
5
G3P
6
P
Glyceraldehyde 3-phosphate
(G3P)
1
Phase 2:
Reduction
P
G3P
(a sugar)
Output
Glucose and
other organic
compounds
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Photorespira,on
In most plants (C3 plants), ini,al xa,on of CO2, via
rubisco, forms a threecarbon compound (3
phosphoglycerate)
In photorespira,on, rubisco adds O2 instead of CO2 in
the Calvin cycle, producing a twocarbon compound
Photorespira,on consumes O2 and organic fuel and
releases CO2 without producing ATP or sugar
Photorespira,on
C4 plants minimize the cost of photorespira,on by
incorpora,ng CO2 into fourcarbon compounds in
mesophyll cells
This step requires the enzyme PEP carboxylase
PEP carboxylase has a higher anity for CO2 than
rubisco does; it can x CO2 even when CO2
concentra,ons are low
These fourcarbon compounds are exported to
bundlesheath cells, where they release CO2 that is
then used in the Calvin cycle
Figure 10.21
Sugarcane
Pineapple
C4
Mesophyll Organic acid
cell
CAM
CO2
Calvin
Cycle
Night
CO2
CO2
Bundlesheath
cell
CO2
1 CO2 incorporated
(carbon fixation) Organic acid
2 CO2 released
to the Calvin
cycle
Sugar
(a) Spatial separation of steps
Calvin
Cycle
Day
Sugar
(b) Temporal separation of steps
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The Importance of Photosynthesis
The energy entering chloroplasts as sunlight gets
stored as chemical energy in organic compounds
Sugar made in the chloroplasts supplies chemical
energy and carbon skeletons to synthesize the organic
molecules of cells
Plants store excess sugar as starch in structures such
as roots, tubers, seeds, and fruits
In addi,on to food produc,on, photosynthesis
produces the O2 in our atmosphere
Figure 10.22
H 2O
CO2
Light
NADP+
ADP
+ Pi
Light
Reactions:
Photosystem II
Electron transport chain
Photosystem I
Electron transport chain
RuBP
3-Phosphoglycerate
Calvin
Cycle
ATP
G3P
Starch
(storage)
NADPH
Chloroplast
O2
Sucrose (export)
Figure 10.UN02
El
ec
El
Primary
acceptor
H 2O
O2
ec
tr
o
ch n tr
ai an
n sp
or
Pq
t
Primary
acceptor
tr
o
ch n tr
ai an
n sp
or
Fd
t
NADP+
reductase
Cytochrome
complex
NADP+
+ H+
NADPH
Pc
Photosystem II
ATP
Photosystem I
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Figure 10.UN06
Stepwise Energy Harvest via NAD+
and the Electron Transport Chain
In cellular respira,on, glucose and other organic
molecules are broken down in a series of steps
Electrons from organic compounds are usually rst
transferred to NAD+, a coenzyme
As an electron acceptor, NAD+ func,ons as an
oxidizing agent during cellular respira,on
Each NADH (the reduced form of NAD+) represents
stored energy that is tapped to synthesize ATP
Stepwise Energy Harvest via NAD+
and the Electron Transport Chain
NADH passes the electrons to the electron transport
chain
Unlike an uncontrolled reac,on, the electron transport
chain passes electrons in a series of steps instead of
one explosive reac,on
O2 pulls electrons down the chain in an energyyielding
tumble
The energy yielded is used to regenerate ATP
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Figure 9.5
H2 + 1/2 O2
2H
1/
2
Free energy, G
Free energy, G
spor
tran
tron ain
ch
Elec
Explosive
release of
heat and light
energy
t
O2
1/
2
+
(from food via NADH)
Controlled
release of
2 H+ + 2 e energy for
synthesis of
ATP
O2
ATP
ATP
ATP
2
e-
2 H+
H 2O
H2O
(a) Uncontrolled reaction
(b) Cellular respiration
Cellular Signaling
Chapter 11
the fight-or-flight response is triggered by a signaling molecule called epinephrine
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Cellular Messaging: External signals are
converted to responses within the cell
Celltocell communica,on is essen,al for both
mul,cellular and unicellular organisms
Biologists have discovered some universal
mechanisms of cellular regula,on
Pathway similari,es suggest that ancestral
signaling molecules evolved in prokaryotes and
were modied later in eukaryotes
Cells most oQen communicate with each other
via chemical signals
Evolu,on of Cell Signaling Microbes
provide a glimpse of
the role of cell signaling in the 1
evolu,on of life
Cells of dierent ma,ng types
locate each other via secreted
factors specic to each type
A signal transduc(on pathway 2
is a series of steps by which a
signal on a cells surface is
converted into a specic
cellular response
Signal transduc,on pathways 3
convert signals on a cells
surface into cellular responses
Receptor
Exchange
of mating
factors
factor
a
a factor
Yeast cell,
Yeast cell,
mating type a
mating type
Mating
a
New a/ cell
a/
1 Individual
rod-shaped
cells
2 Aggregation
in progress
0.5 mm
3 Spore-forming
structure
(fruiting body)
2.5 mm
Fruiting bodies
The concentration of signaling molecules allows bacteria to sense
local population density
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Local and LongDistance Signaling
Plasma membranes
Cells in a mul,cellular
organism communicate
by chemical messengers
Animal and plant cells
Gap junctions
have cell junc,ons that
between animal cells
directly connect the
(a) Cell junctions
cytoplasm of adjacent
cells
Plasmodesmata
between plant cells
In local signaling, animal
cells may communicate
by direct contact, or (b) Cell-cell recognition
cellcell recogni,on
Local and LongDistance Signaling
Local signaling
Long-distance signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling
Endocrine cell
Neurotransmitter
diffuses across
synapse.
Secretory
vesicle
Target cell
is stimulated.
Blood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(b) Synaptic signaling
(c) Endocrine (hormonal) signaling
Local and LongDistance Signaling
In many other cases, animal cells communicate
using local regulators, messenger molecules
that travel only short distances
In longdistance signaling, plants and animals
use chemicals called hormones
The ability of a cell to respond to a signal
depends on whether or not it has a receptor
specic to that signal
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Local and LongDistance Signaling
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Target cell
Secreting
cell
Neurotransmitter
diffuses across
synapse.
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid.
Target cell
is stimulated.
(b) Synaptic signaling
(a) Paracrine signaling
Long-distance signaling
Endocrine cell
Blood
vessel
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
The Three Stages of Cell Signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Relay molecules in a signal transduction
pathway
Activation
of cellular
response
Signaling
molecule
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The Three Stages of Cell Signaling
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane
1 Reception
Receptor
Signaling
molecule
The Three Stages of Cell Signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Signaling
molecule
The Three Stages of Cell Signaling
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Relay molecules in a signal transduction
pathway
Activation
of cellular
response
Signaling
molecule
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Recep,on: A signaling molecule binds
to a receptor protein, causing it to
change shape
The binding between a signal molecule (ligand)
and receptor is highly specic
A shape change in a receptor is oQen the ini,al
transduc,on of the signal
Most signal receptors are plasma membrane
proteins
Receptors in the Plasma Membrane
Most watersoluble signal molecules bind to specic sites on
receptor proteins that span the plasma membrane
There are three main types of membrane receptors
G proteincoupled receptors
Receptor tyrosine kinases
Ion channel receptors
G proteincoupled receptors (GPCRs) are the largest family of
cellsurface receptors
A GPCR is a plasma membrane receptor that works with the help
of a G protein
The G protein acts as an on/o switch: If GDP is bound to the G
protein, the G protein is inac,ve
Receptors in the Plasma Membrane
G protein-coupled
receptor
CYTOPLASM
1
Plasma
membrane
Activated
receptor
Signaling
molecule
Inactive
enzyme
GTP
GDP
GDP
Enzyme
G protein
(inactive)
2
GDP
GTP
Activated
enzyme
GTP
GDP
Pi
3
Cellular response
4
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Receptors in the Plasma Membrane
Receptor tyrosine kinases (RTKs) are membrane
receptors that a`ach phosphates to tyrosines
A receptor tyrosine kinase can trigger mul,ple
signal transduc,on pathways at once
Abnormal func,oning of RTKs is associated with
many types of cancers
Receptors in the Plasma Membrane
Signaling
molecule (ligand)
helix in the
membrane
Ligand-binding site
Signaling
molecule
Tyr
Tyrosines
Tyr
Tyr
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
1
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
2
Activated relay
proteins
Tyr
P Tyr
Tyr
Tyr
P Tyr
Tyr
P Tyr
P Tyr
Tyr P
Tyr
6
ATP
6 ADP
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
Activated tyrosine
kinase regions
(unphosphorylated
3 dimer)
Cellular
response 1
Tyr P
P Tyr
P Tyr
Tyr P
Tyr P
Tyr
Tyr P
Tyr P
Cellular
response 2
Inactive
relay proteins
4
Receptors in the Plasma Membrane
1
3
2
Signaling
molecule
(ligand)
Gate
closed
Ions
Plasma
Ligand-gated
membrane
ion channel receptor
Gate closed
Gate
open
Cellular
response
A ligand-gated ion channel receptor acts as a gate when the
receptor changes shape
When a signal molecule binds as a ligand to the receptor, the gate
allows specific ions, such as Na+ or Ca2+, through a channel in the
receptor
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Intracellular Receptors
Intracellular receptor proteins are
found in the cytosol or nucleus of
target cells
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
Small or hydrophobic chemical
messengers can readily cross the
membrane and ac,vate receptors
Examples of hydrophobic messengers
are the steroid and thyroid hormones
of animals
An ac,vated hormonereceptor
complex can act as a transcrip,on
factor, turning on specic genes
DNA
mRNA
NUCLEUS
New protein
CYTOPLASM
Figure 11.9-1
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-2
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
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Figure 11.9-3
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
NUCLEUS
CYTOPLASM
Figure 11.9-4
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
Figure 11.9-5
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
mRNA
NUCLEUS
New protein
CYTOPLASM
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Signal Transduc,on Pathways
Signal transduc,on usually involves mul,ple steps. Cascades of
molecular interac,ons relay signals from receptors to target
molecules
Mul,step pathways can amplify a signal: A few molecules can
produce a large cellular response
Mul,step pathways provide more opportuni,es for coordina,on
and regula,on of the cellular response
The molecules that relay a signal from receptor to response are
mostly proteins
Like falling dominoes, the receptor ac,vates another protein, which
ac,vates another, and so on, un,l the protein producing the
response is ac,vated
At each step, the signal is transduced into a dierent form, usually a
shape change in a protein
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
ATP
P
n
Active
protein
kinase
2
tio
e
ad
sc
ca
Pi
ADP
PP
yla
or
ph
os
Inactive
protein kinase
2
Ph
Active
protein
kinase
1
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Protein Phosphoryla,on and
Dephosphoryla,on
In many pathways, the signal is transmi`ed by a
cascade of protein phosphoryla,ons
Protein kinases transfer phosphates from ATP to
protein, a process called phosphoryla,on
Protein phosphatases remove the phosphates
from proteins, a process called dephosphoryla,on
This phosphoryla,on and dephosphoryla,on
system acts as a molecular switch, turning
ac,vi,es on and o or up or down, as required
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Small Molecules and Ions as Second
Messengers
The extracellular signal molecule (ligand) that
binds to the receptor is a pathways rst
messenger
Second messengers are small, nonprotein, water
soluble molecules or ions that spread throughout a
cell by diusion
Second messengers par,cipate in pathways
ini,ated by GPCRs and RTKs
Cyclic AMP and calcium ions are common second
messengers
Small Molecules and Ions as Second
Messengers
Adenylyl cyclase
Phosphodiesterase
H 2O
Pyrophosphate
P Pi
ATP
cAMP
AMP
Cyclic AMP (cAMP) is one of the most widely used
second messengers
Adenylyl cyclase, an enzyme in the plasma membrane,
converts ATP to cAMP in response to an extracellular
signal
Small Molecules and Ions as Second
Messengers
Many signal molecules trigger forma,on of cAMP
Other components of cAMP pathways are G
proteins, G proteincoupled receptors, and protein
kinases
cAMP usually ac,vates protein kinase A, which
phosphorylates various other proteins
Further regula,on of cell metabolism is provided
by Gprotein systems that inhibit adenylyl cyclase
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EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
CYTOSOL
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
Ca2+
(second
messenger)
CYTOSOL
EXTRACELLULAR
FLUID
Signaling molecule
(first messenger)
G protein
DAG
GTP
G protein-coupled
receptor
Phospholipase C
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Ca2+
Ca2+
CYTOSOL
Various
proteins
activated
Cellular
responses
(second
messenger)
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Small Molecules and Ions as Second
Messengers
Calcium ions (Ca2+) act as a second messenger in
many pathways
Calcium is an important second messenger
because cells can regulate its concentra,on
A signal relayed by a signal transduc,on pathway
may trigger an increase in calcium in the cytosol
Pathways leading to the release of calcium involve
inositol triphosphate (IP3) and diacylglycerol
(DAG) as addi,onal second messengers
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Cell signaling leads to regulation of transcription or cytoplasmic activities
FineTuning of the Response
There are four aspects of netuning to consider
Amplica,on of the signal (and thus the response)
Specicity of the response
Overall eciency of response, enhanced by
scaolding proteins
Termina,on of the signal
Enzyme cascades amplify the cells response
At each step, the number of ac,vated products is
much greater than in the preceding step
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The Specicity of Cell Signaling and
Coordina3on of the Response
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Activation
or inhibition
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses.
Response 5
Response 4
Cell C. Cross-talk occurs
between two pathways.
Cell D. Different receptor
leads to a different
response.
The Specicity of Cell Signaling and
Coordina3on of the Response
Dierent kinds of cells have dierent collec,ons
of proteins
These dierent proteins allow cells to detect
and respond to dierent signals
Even the same signal can have dierent eects
in cells with dierent proteins and pathways
Pathway branching and crosstalk further help
the cell coordinate incoming signals
Signaling Eciency: Scaolding
Proteins and Signaling Complexes
Signaling
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Three
different
protein
kinases
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Signaling Eciency: Scaolding
Proteins and Signaling Complexes
Scaolding proteins are large relay proteins to which
other relay proteins are a`ached
Scaolding proteins can increase the signal transduc,on
eciency by grouping together dierent proteins involved
in the same pathway
In some cases, scaolding proteins may also help ac,vate
some of the relay proteins
If ligand concentra,on falls, fewer receptors will be bound
Unbound receptors revert to an inac,ve state causing
termina,on of the signal
Apoptosis of a human white blood cell
2 m
normal
apoptotic
Apoptosis integrates mul,ple
cellsignaling pathways
Apoptosis is programmed or controlled cell death
Components of the cell are packaged into vesicles
that are digested by scavenger cells
Apoptosis prevents enzymes from leaking out of a
dying cell and damaging neighboring cells
The role of apoptosis in embryonic development
was rst studied in Caenorhabdi3s elegans
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Apoptosis and development
Interdigital tissue
Cells undergoing
apoptosis
1 mm
Space between
digits
Eect of apoptosis during paw development in the mouse
Apoptosis is important in shaping an
organism during embryonic development
Apopto,c Pathways and the Signals
That Trigger Them
Ced-9
protein (active)
inhibits Ced-4
activity
Mitochondrion
Ced-9
(inactive)
Deathsignaling
molecule
Active Active
Ced-4 Ced-3
Receptor
for deathsignaling
molecule
Ced-4 Ced-3
Inactive proteins
(a) No death signal
Cell
forms
blebs
Activation
cascade
Other
proteases
Nucleases
(b) Death signal
Apopto,c Pathways and the Signals
That Trigger Them
Caspases are the main proteases (enzymes that cut up proteins)
that carry out apoptosis
Apoptosis can be triggered by
An extracellular deathsignaling ligand
DNA damage in the nucleus
Protein misfolding in the endoplasmic re,culum
Apoptosis evolved early in animal evolu,on and is essen,al for
the development and maintenance of all animals
Apoptosis may be involved in some diseases (for example,
Parkinsons and Alzheimers); interference with apoptosis may
contribute to some cancers
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