INTRODUCTION TO THE BIOLOGICAL

PROCESSES IN CELL
 OBJECTIVES
• TO KNOW THE COMMON FORMS OF ENERGY IN CELL
• TO KNOW THREE MAJOR PROCESSES IN CELLULAR
RESPIRATION
• TO KNOW HOW CELL PRODUCES ATP IN THE CONDITION
WITHOUT OXYGEN
• TO KNOW THE PATHWAYS OF PHOTOSYNTHESIS
• TO KNOW HOW THE CELLS COMMUNICATE WITH EACH
OTHER
• TO UNDERSTAND THE WAY FROM SIGNAL COMING TO THE
CELLULAR RESPONSE TO THE SIGNALS
 CONTENT
• CELLULAR RESPIRATION
– THE ENERGY FLOW AND CHEMICAL RECYCLING IN ECOSYSTEMS
– THE STRUCTURE OF ATP, NAD+
– THE GLYCOLYSIS, KREB CYCLE, AND ELECTRON TRANSPORT CHAIN
– THE PRODUCTION OF ATP WITHOUT OXYGEN

• PHOTOSYNTHESIS
- PHOTOSYNTHESIS IN THE NATURE
- THE PATHWAYS IN PHOTOSYNTHESIS

• CELL COMMUNICATION
– OVERVIEW OF CELL SIGNALING
– SIGNAL RECEPTION AND THE INITIATION OF TRANSDUCTION
– SIGNAL TRANDUCTION PATHWAYS
– CELLULAR REPONSES TO SIGNALS
 –THE ENERGY FLOW AND CHEMICAL RECYCLING IN ECOSYSTEMS

Fig 2.1. Energy flow and chemical recycling in ecosystems.

The mitochondria of eukaryotes (including plants and algae) use the organic products of photosynthesis
as fuel for cellular respiration, which also consumes the oxygen produced by photosynthesis.
Respiration harvests the energy stored in organic molecules to generate ATP, which powers most
cellular work. The waste products of respiration, carbon dioxide and water, are the very substances that
chloroplasts use as raw materials for photosynthesis. Thus, the chemical elements essential to life are
recycled. But energy is not: It flows into an ecosystem as sunlight and leaves as heat
THE STRUCTURE OF ATP, NAD+

- The molecule known as ATP, short for adenosine triphosphate, is the central character in
bioenergetics

- The triphosphate tail of ATP is the chemical equivalent of a loaded spring; the close packing of the
three negatively charged phosphate groups is an unstable, energy-storing arrangement. The chemical
"spring" tends to "relax" by losing the terminal phosphate

- The cell taps this energy source by using enzymes to transfer phosphate groups from ATP to other
compounds, which are then said to be phosphorylated. Phosphorylation primes a molecule to undergo
some kind of change that performs work, and the molecule loses its phosphate group in the process
ATP = ADP + Pi

- For example, a working muscle cell, for example, recycles its ATP at a rate of about 10 million
molecules per second. To understand how cellular respiration regenerates ATP, we need to examine
the fundamental chemical processes known as oxidation and reduction.
Fig 2.2. The
structure and
hydrolysis of ATP.
The hydrolysis of ATP
yields inorganic
phosphate and ADP.
In the cell, most
hydroxyl groups of
phosphates are
ionized (--O-).
 Fig 2.3. NAD+ as an electron shuttle.
The full name for NAD+, nicotinamide adenine dinucleotide, describes its structure; the
molecule consists of two nucleotides joined together. (Nicotinamide is a nitrogenous base,
although not one that is present in DNA or RNA.) The enzymatic transfer of two electrons
and one proton from some organic substrate to NAD+ reduces the NAD+ to NADH. Most of
the electrons removed from food are transferred initially to NAD+.
- Electrons lose very little of their potential energy when they are transferred from food to NAD+.
- Each NADH molecule formed during respiration represents stored energy that can be tapped to
make ATP when the electrons complete their "fall" from NADH to oxygen

- How do electrons extracted from food and stored by NADH finally reach O2?
(1) The reaction between H2 and O2 to form H2O + gases = explosion + release of energy
(2) Cellular respiration also brings H2 and O2 together to form H2O, but there are two important
differences. First, in cellular respiration, the H2 that reacts with O2 is derived from organic
molecules. Second, respiration uses an electron transport chain to break the fall of electrons to
O2 into several energy-releasing steps instead of one explosive reaction

- The transport chain consists of a number of molecules, mostly proteins, built into the inner
membrane of a mitochondrion.
- Electrons removed from food are shuttled by NADH to the "top" end of the chain. At the "bottom"
end, O2 captures these electrons along with H2, forming water.

- Thus, electrons removed from food by NAD+ fall down the electron transport chain to a far more
stable location in the electronegative O2 atom.

Food  NADH  electron transport chain 8n oxygen

 Fig 2.4. An introduction to electron transport chains.
(a) The uncontrolled exergonic reaction of H2 with O2 to form H2O releases a large amount
of energy in the form of heat and light: an explosion.
(b) In cellular respiration, the same reaction occurs in stages: An electron transport chain
breaks the "fall" of electrons in this reaction into a series of smaller steps and stores some
of the released energy in a form that can be used to make ATP.
(The rest of the energy is released as heat.)
THE PROCESS OF CELLULAR RESPIRATION

* Respiration involves glycolysis, the Krebs cycle, and electron transport:

an overview
* Glycolysis harvests chemical energy by oxidizing glucose to pyruvate:
a closer look
* The Krebs cycle completes the energy-yielding oxidation of organic molecules:
a closer look
* The inner mitochondrial membrane couples electron transport to ATP synthesis:
a closer look
* Cellular respiration generates many ATP molecules for each sugar molecule it oxidizes:
a review
 Respiration involves glycolysis, the Krebs cycle,
and electron transport: an overview

Fig 9-6. An overview of cellular respiration.

- In a eukaryotic cell, glycolysis occurs outside the mitochondria in the cytosol.

The Krebs cycle and the electron transport chains are located inside the mitochondria.
- During glycolysis, each glucose molecule is broken down into two molecules of the
compound pyruvate.
- The pyruvate crosses the double membrane of the mitochondrion to enter the matrix,
where the Krebs cycle decomposes it to carbon dioxide.
- NADH or FADH2 transfers electrons from molecules undergoing glycolysis and the
Krebs cycle to electron transport chains, which are built into the inner mitochondrial
membrane.
- The electron transport chain converts the chemical energy to a form that can be used to
drive oxidative phosphorylation, which accounts for most of the ATP generated by
cellular respiration.
- A smaller amount of ATP is formed directly during glycolysis and the Krebs cycle by
substrate-level phosphorylation.

(1) Glycolysis (color-coded teal throughout the chapter)

(2) The Krebs cycle (color-coded salmon)
(3) The electron transport chain and oxidative phosphorylation (color-coded violet )
Respiration is a cumulative function of 3 metabolic stages
(1) Glycolysis (color-coded teal throughout the chapter) - cytosol
Glycolysis, begins the degradation by breaking: glucose = two molecules pyruvate

(2) The Krebs cycle (color-coded salmon) - mitochondrial matrix

Decomposing a derivative of pyruvate to CO2

(3) The electron transport chain and oxidative phosphorylation (color-coded violet)
the electron transport chain accepts electrons from the breakdown products of the first two stages
(usually via NADH) and passes these electrons from one molecule to another

- The energy released at each step of the chain is stored in a form the mitochondrion can use to
make ATP.
- This mode of ATP synthesis is called oxidative phosphorylation because it is powered by the
redox reactions that transfer electrons from food to O2.

- Oxidative phosphorylation accounts for almost 90% of the ATP generated by respiration
- A smaller amount of ATP is formed by substrate-level phosphorylation when an enzyme transfers
a phosphate group from a substrate molecule to ADP. "Substrate molecule" here refers to an
organic molecule generated during the catabolism of glucose.

cell respiration
glucose = CO2 + H2O + 38 molecules of ATP
 Fig 2.6. Substrate-level phosphorylation.
Some ATP is made by direct enzymatic transfer of a phosphate group from a substrate to
ADP. The phosphate donor in this case is phosphoenolpyruvate (PEP), which is formed
from the breakdown of sugar during glycolysis
GLYCOLYSIS

Glycolysis harvests chemical energy by oxidizing glucose to pyruvate:

a closer look

- Glucose, a six-carbon sugar, is split into two three-carbon sugars. These

smaller sugars are then oxidized and their remaining atoms rearranged to form
two molecules of pyruvate. (Pyruvate is the ionized form of a three-carbon
acid, pyruvic acid.)

- The pathway of glycolysis consists of ten steps, each catalyzed by a

specific enzyme. We can divide these ten steps into two phases: The energy
investment phase includes the first five steps, and the energy payoff phase
includes the next five steps.
- During the energy investment phase, the cell actually spends ATP to
phosphorylate the fuel molecules and NAD+ is reduced to NADH by
oxidation of the food

glycolysis
glucose = 2 ATP + 2 NADH
Fig 2.7. The energy input and output of glycolysis
 Fig 2.8. A closer look at glycolysis.
The orientation diagram at the right relates glycolysis to the whole process of respiration.
Do not let the chemical detail in the main diagram block your view of glycolysis as a
source of ATP and NADH.
 Fig 2.9. A closer look at glycolysis.
The orientation diagram at the right relates glycolysis to the whole process of respiration.
Do not let the chemical detail in the main diagram block your view of glycolysis as a
source of ATP and NADH.
THE KREBS CYCLE

The Krebs cycle completes the energy-yielding oxidation of organic

molecules: a closer look

(1) Pyruvate’s carboxyl group, which is already fully oxidized and thus has
little chemical energy, is removed and given off as a molecule of CO2. (This
is the first step in respiration where CO2 is released.)   

(2) The remaining two-carbon fragment is oxidized to form a compound

named acetate (the ionized form of acetic acid). An enzyme transfers the
extracted electrons to NAD+, storing energy in the form of NADH.   

(3) Finally, coenzyme A, a sulfur-containing compound derived from a B

vitamin, is attached to the acetate makes the acetyl group (the attached
acetate) very reactive. Acetyl CoA, is now ready to feed its acetate into the
Krebs cycle for further oxidation.
 Fig 2.10. Conversion of pyruvate to acetyl CoA, the junction between glycolysis and
the Krebs cycle.
A complex of several enzymes catalyzes the three numbered steps, which are described in
the text. The acetyl CoA will enter the Krebs cycle. The CO2 molecule will diffuse out of the
cell.
The Kreb cycle has 8 steps, each catalyzed by a specific enzyme .
- 2 C enter in the relatively reduced form of acetate (step 1), and
- 2 C leave in the completely oxidized form of CO2 (steps 3 and 4).
- Subsequent steps decompose the citrate back to oxaloacetate, giving off CO2 as "exhaust." It is
this regeneration of oxaloacetate that accounts for the "cycle" in the Krebs cycle .

Most of the energy harvested by the oxidative steps of the cycle is conserved in NADH
- For each acetate that enters the cycle, 3 NAD+ are reduced to NADH (steps 3, 4, and 8).
- In one oxidative reaction (step 6) electrons are transferred to FAD (flavin adenine dinucleotide,
derived from riboflavin, a B vitamin). The reduced form, FADH2, donates its electrons to the
electron transport chain, as does NADH.
- Step 5, that forms 1 ATP directly by substrate-level phosphorylation,
- But most of the ATP output of respiration results from oxidative phosphorylation, when the
NADH and FADH2 produced by the Krebs cycle relay the electrons extracted from food to the
electron transport chain
 (1)

(2)
(8)

(3)
(7)

(4)
(6)

(5)
Fig 2.11. A closer look at the Krebs cycle.
In the chemical structures, red type traces the fate of the two carbon atoms that enter the
cycle via acetyl CoA (step 1), and blue type indicates the two carbons that exit the cycle as
CO2 in steps 3 and 4. Notice that carboxylic acids are represented in their ionized forms, as
--COO-. For example, citrate is the ionized form of citric acid.
 Fig 2.12. 
A summary of the Krebs cycle.
The cycle functions as a metabolic
furnace that oxidizes organic fuel
derived from pyruvate, the product of
glycolysis. This diagram summarizes the
inputs and outputs as pyruvate is broken
down to three molecules of CO2, and it
includes the molecule of CO2 released
during pre-Krebs cycle conversion of
pyruvate to acetyl CoA. The cycle
generates 1 ATP per turn by substrate
phosphorylation, but most of the
chemical energy is transferred during the
redox reactions to NAD+ and FAD. The
reduced coenzymes, NADH and FADH2,
shuttle their cargo of high-energy
electrons to the electron transport chain,
which uses the energy to synthesize
ATP by oxidative phosphorylation. (To
calculate the inputs and outputs on a
"per-glucose" basis, multiply by 2,
because each glucose molecule is split
during glycolysis into two pyruvate
molecules.)
ELECTRON TRANSPORT CHAIN
The inner mitochondrial membrane couples electron transport to ATP synthesis: a closer
look

How cells harvest the energy of food to make ATP ?

- But metabolic components of respiration we have dissected so far, glycolysis and the Krebs cycle,
produce only 4 ATP per glucose molecule, all by substrate-level phosphorylation: 2 ATP (glycolysis)
and 2 ATP (Krebs cycle).
- At this point, molecules of NADH (and FADH2) account for most of the energy extracted from the
food
- These electron escorts link glycolysis and the Krebs cycle to the machinery for oxidative
phosphorylation, which uses energy released by the electron transport chain to power ATP
synthesis.

2.4.1. The pathway of electron transport

- Fig 2.13 shows the sequence of electron carriers in the electron transport chain and the drop in free
energy as electrons travel down the chain
- Electrons removed from food (during glycolysis and the Krebs cycle) are transferred by NADH to
flavoprotein, the first molecule of the electron transport chain. This molecule is a prosthetic group
called flavin mononucleotide
- In the next redox reaction, the flavoprotein returns to its oxidized form as it passes electrons to an
iron-sulfur protein (FeS ), one of a family of proteins with both iron-sulfur tightly bound.
- The iron-sulfur protein then passes the electrons to ubiquinone (Q ). This electron carrier is a
lipid, the only member of the electron transport chain that is not a protein.
- Most of the remaining electron carriers between Q and O2 are proteins called cytochromes (cyt).
- Another source of electrons for the transport chain is FADH2 (the other reduced product of the
Krebs cycle) adds its electrons to the electron transport chain at a lower energy level than NADH
 Fig 2.13. 
Free-energy change during electron transport.
Each member of the chain oscillates between a
reduced state and an oxidized state. A component
of the chain becomes reduced when it accepts
electrons from its "uphill" neighbor, which has a
lower affinity for electrons (is less electronegative).
It then returns to its oxidized form as it passes
electrons to its "downhill," more electronegative,
neighbor. At the bottom of the chain is oxygen,
which is very electronegative. The overall energy
drop for electrons traveling from NADH to oxygen
is 53 kcal/mol, but this fall is broken up into a
series of smaller steps by the electron transport
chain. The various molecules of the electron
transport chain, shown as light purple ovals here,
are described in the text. Most of these electron
carriers are grouped into multiprotein complexes,
shown here and in darker purple.
How does the mitochondrion couple this electron transport and energy release to ATP
synthesis?
- The answer is a mechanism called chemiosmosis.
- The electron transport chain makes no ATP
directly.

2.4.2. Chemiosmosis: The energy-coupling mechanism

-Populating the inner membrane of the mitochondrion are many copies of a protein complex called
ATP synthase, the enzyme that actually makes ATP from ADP and inorganic phosphate
: ADP + Pi = ATP

- ATP synthase works like an ion pump running in reverse.

- In the reverse of that process, ATP synthase uses the energy of an existing ion gradient to power
ATP synthesis.

- The power source for the ATP synthase is a difference in the concentration of H+ on opposite
sides of the inner mitochondrial membrane
 Fig 2.14. 
ATP synthase, a
molecular mill.
The ATP synthase
protein complex
functions as a mill,
powered by the flow of
hydrogen ions. This
complex resides in
mitochondrial and
chloroplast
membranes of
eukaryotes and in the
plasma membranes of
prokaryotes. ATP
synthase has three
main parts: a rotor, a
rod, and a knob. Each
part consists of a
number of protein
subunits
How does the mitochondrial membrane generate and maintain an H+ gradient ?

- That is the function of the electron transport chain, which is shown in its mitochondrial location in
fig 2.15
- The chain is an energy converter that uses the exergonic flow of electrons to pump H+ across
the membrane, from the matrix into the intermembrane space

- The ATP synthases are the only patches of the membrane that are freely permeable to H+.

- The ions pass through a channel in ATP synthase, and this protein complex uses the exergonic
flow of H+ to drive the oxidative phosphorylation of ADP.

- Thus, an H+ gradient across a membrane couples the redox reactions of the electron transport
chain to ATP synthesis.

- This coupling mechanism is called chemiosmosis (from the Greek osmos, push), a term that
highlights the connection between the chemical reaction that makes ATP and transport across a
membrane.
 Fig 2.15. Chemiosmosis couples the electron transport chain to ATP synthesis.
NADH shuttles high-energy electrons extracted from food during glycolysis and the Krebs cycle to an electron transport chain built into the inner
mitochondrial membrane. The gold arrow traces the transport of electrons, which finally pass to oxygen at the "downhill" end of the chain to form
water. As fig9.13 showed, most of the electron carriers of the chain are grouped into three complexes, each represented here by a purple blob
embedded in the membrane. Two mobile carriers, ubiquinone (Q) and cytochrome c, move rapidly along the membrane, ferrying electrons
between the three large complexes. As each complex of the chain accepts and then donates electrons, it pumps hydrogen ions (protons) from the
mitochondrial matrix into the intermembrane space. Thus, chemical energy originally harvested from food is transformed into a proton-motive
force, a gradient of H+ across the membrane. The hydrogen ions flow back, down their gradient, through a channel in an ATP synthase, another
protein complex built into the membrane. The ATP synthase harnesses the proton-motive force to phosphorylate ADP, forming ATP. (This
phosphorylation is called oxidative because it is driven by the loss of electrons from food molecules.) The use of an H+ gradient (proton-motive
force) to transfer energy from redox reactions to cellular work (ATP synthesis, in this case) is called chemiosmosis.
How does the electron transport chain pump hydrogen ions ?

- In answer to the first question, researchers have found that certain members of the electron
transport chain accept and release protons (H+) along with electrons.
- At certain steps along the chain, electron transfers cause H+ to be taken up and released back
into the surrounding solution.
- The electron carriers are spatially arranged in the membrane in such a way that H+ is accepted
from the mitochondrial matrix and deposited in the intermembrane space (see fig9.15 again).

And How does the ATP synthase use H+ backflow to make ATP ?

- The ATP synthase complex consists of three main parts: (1) a cylindrical rotor within the inner
mitochondrial membrane, (2) a knob protruding into the mitochondrial matrix, and (3) an internal rod
connecting the two.
- When hydrogen ions flow through the cylinder down their gradient, they cause the cylinder and the
attached rod to rotate, much as a rushing stream turns a waterwheel.
- The spinning rod brings about a conformational change in the knob, activating catalytic sites where
ADP and inorganic phosphate combine to make ATP
Chemiosmosis also occurs elsewhere and in other variations:
- In general terms, chemiosmosis is an energy-coupling mechanism that uses energy stored in
the form of an H+ gradient across a membrane to drive cellular work.
- In mitochondria, the energy for gradient formation comes from exergonic redox reactions, and
ATP synthesis performed.
- Chloroplasts use chemiosmosis to generate ATP during photosynthesis; in these organelles, light
(rather than chemical energy) drives both electron flow down (an electron transport chain) and H+
gradient formation.
- Prokaryotes, which lack both mitochondria and chloroplasts, generate H+ gradients across their
plasma membranes
 Cellular respiration generates many ATP molecules
for each sugar molecule it oxidizes: a review

- Now that we have looked more closely at the key processes of cellular respiration, let’s return to its
overall function: harvesting the energy of food for ATP synthesis

- During respiration, most energy flows in this sequence:

Glucose NADH  electron transport chain  protonmotive force  ATP

- Fig2.16:
(1) ATP (1 glucose molecule oxidized) = few ATP produced directly by substrate-level
phosphorylation (during glycolysis and the Krebs cycle) + many more ATP generated by oxidative
phosphorylation
(2) 1 NADH that transfers a pair of electrons from food to the electron transport chain to generate a
maximum of about 3 ATP.
(3) The Krebs cycle also supplies electrons to the electron transport chain via FADH2 (1 FADH2 # 2
ATP)
(4) NADH produced by glycolysis in the cytosol. The 2 electrons of NADH (captured in glycolysis) must
be conveyed into the mitochondrion by one of several electron shuttle systems. Depending on which
shuttle is operating. If the electrons are passed to FAD, only about 2 ATP can result from each cytosolic
NADH2. If passed to mitochondrial NAD+, the yield is closer to 3 ATP.

1 glucose = energy-efficient type of shuttle is active = 34ATP (produced by oxidative

phosphorylation) + 4ATP (from substrate-level phosphorylation) = 38ATP

Complete oxidation 1 glucose = releases 686 kcal of energy (DG = -686 kcal/mol). Phosphorylation of
ADP to form ATP stores 7.3 kcal/1ATP. The efficiency of respiration is 7.3 X 38 (maximum ATP yield per
glucose) / 686 = 40% . The rest of the stored energy (60%) is lost as heat. We use some of this heat to
maintain our relatively high body temperature (37°C)
 Fig 2.16. Review:
how each molecule of glucose yields many ATP molecules during cellular respiration. The
text explains why the yield of 38 ATP per glucose is only an estimate of the maximum output
 * Fermentation enables some cells to produce ATP without the help of oxygen

Because most of the ATP generated by cellular respiration is the work of oxidative phosphorylation,
our estimate of ATP yield from respiration is contingent upon an adequate supply of oxygen to the
cell. Without the electronegative oxygen to pull electrons down the transport chain, oxidative
phosphorylation ceases. However, fermentation provides a mechanism by which some cells can
oxidize organic fuel and generate ATP without the help of oxygen
 Fermentation enables some cells to produce ATP
without the help of oxygen

How can food be oxidized without oxygen ?

- Oxidation refers to the loss of electrons to any electron acceptor, not just to O2.
- Glycolysis oxidizes glucose to 2 pyruvate. The oxidizing agent of glycolysis is NAD+, not O2.
- Overall, glycolysis is exergonic, and some of the energy made available is used to produce 2 ATP
(net) by substrate-level phosphorylation.
- If O2 is present, then additional ATP is made by oxidative phosphorylation when NADH passes
electrons removed from glucose to the electron transport chain.
- But glycolysis generates 2 ATP whether O2 is present or not--that is, whether conditions are aerobic
or anaerobic (from the Greek aer, air, and bios, life; the prefix an - means "without").

- Anaerobic catabolism of organic nutrients can occur by fermentation.

- Fermentation is an extension of glycolysis that can generate ATP solely by substrate-level
phosphorylation--as long as there is a sufficient supply of NAD+ to accept electrons during the
oxidation step of glycolysis.
- Without some mechanism to recycle NAD+ from NADH, glycolysis would soon deplete the cell’s
pool of NAD+ and shut itself down for lack of an oxidizing agent.

- Under aerobic conditions, NAD+ is recycled productively from NADH by the transfer of electrons to
the electron transport chain. The anaerobic alternative is to transfer electrons from NADH to
pyruvate, the end product of glycolysis.
- Fermentation consists of glycolysis plus reactions that regenerate NAD+ by transferring electrons
from NADH to pyruvate or derivatives of pyruvate.
- The NAD+ can then be reused to oxidize sugar by glycolysis, which nets 2 ATP by substrate-level
phosphorylation
- There are many types of fermentation, differing in the waste products formed from pyruvate. Two
common types are alcohol fermentation and lactic acid fermentation.

- In alcohol fermentation (fig2.17a), Pyruvate is converted to ethanol (ethyl alcohol) in two steps. (1)
The first step releases CO2 from the pyruvate, which is converted to the two-carbon compound
acetaldehyde. (2) In the second step, acetaldehyde is reduced by NADH to ethanol. This
regenerates the supply of NAD+ needed for glycolysis

- During lactic acid fermentation (fig2.17b), pyruvate is reduced directly by NADH to form lactate as
a waste product, with no release of CO2

- Human muscle cells make ATP by lactic acid fermentation when O2 is scarce
 Fig 2.17. Fermentation. In the absence of oxygen,
many cells use fermentation to produce ATP by substrate-level phosphorylation.
Pyruvate, the end product of glycolysis, serves as an electron acceptor for oxidizing NADH back to
NAD+, which can then be reused in glycolysis. Two of the common waste products formed from
fermen-tation are (a) ethanol and (b) lactate, the ionized form of lactic acid.
 Fig 2.17. Fermentation. In the absence of oxygen,
many cells use fermentation to produce ATP by substrate-level phosphorylation. Pyruvate, the
end product of glycolysis, serves as an electron acceptor for oxidizing NADH back to NAD+, which can
then be reused in glycolysis. Two of the common waste products formed from fermen-tation are (a)
ethanol and (b) lactate, the ionized form of lactic acid.
Fermentation and respiration compared

- Fermentation and cellular respiration are anaerobic and aerobic alternatives, respectively, for
producing ATP by harvesting the chemical energy of food.
Both pathways use glycolysis to oxidize glucose and other organic fuels to pyruvate, with a net
production of 2 ATP by substrate-level phosphorylation.
And in both fermentation and respiration, NAD+ is the oxidizing agent that accepts electrons from food
during glycolysis

- A key difference is the contrasting mechanisms for oxidizing NADH back to NAD+, which is required
to sustain glycolysis.
- In fermentation, the final electron acceptor is an organic molecule such as pyruvate (lactic acid
fermentation) or acetaldehyde (alcohol fermentation).
In respiration, by contrast, the final acceptor for electrons from NADH is O2.

- Thus, cellular respiration harvests much more energy from each sugar molecule than fermentation
can
Respiration: 38 ATP
Fermentation: 2 ATP (from 1 glucose)

- In a facultative anaerobe, pyruvate is a fork in the metabolic road that leads to two alternative
catabolic routes. Under aerobic conditions, pyruvate can be converted to acetyl CoA, and oxidation
continues in the Krebs cycle. Under anaerobic conditions, pyruvate is diverted from the Krebs cycle,
serving instead as an electron acceptor to recycle NAD+.

3.1.2. The evolutionary significance of glycosis

- The role of glycolysis in both fermentation and respiration has an evolutionary basis. Ancient
prokaryotes probably used glycolysis to make ATP long before oxygen was present in Earth’s
atmosphere
 Fig 2.18. Pyruvate as a key juncture in catabolism.
Glycolysis is common to fermentation and respiration. The end product of glycolysis, pyruvate,
represents a fork in the catabolic pathways of glucose oxidation. In a cell capable of both respiration and
fermentation, pyruvate is committed to one of those two pathways, usually depending on whether or not
oxygen is present.
 PHOTOSYNTHESIS
  

PHOTOSYNTHESIS IN NATURE
- Plants and other autotrophs are the producers of the biosphere
- Chloroplasts are the sites of photosynthesis in plants

THE PATHWAYS OF PHOTOSYNTHESIS

- Evidence that chloroplasts split water molecules enabled researchers to track atoms through
photosynthesis
- The light reactions and the Calvin cycle cooperate in converting light energy to the chemical energy
of food: an overview
- The light reactions convert solar energy to the chemical energy of ATP and NADPH: a closer look
- The Calvin cycle uses ATP and NADPH to convert CO 2 to sugar: a closer look
 PHOTOSYNTHESIS IN NATURE

* Plants and other autotrophs are the producers of the biosphere

* Chloroplasts are the sites of photosynthesis in plants
 Plants and other autotrophs are the producers of the biosphere

- Photosynthesis nourishes almost all of the living world directly or indirectly.

- An organism acquires the organic compounds it uses for energy and carbon skeletons by one of
2 major modes: autotrophic or heterotrophic nutrition

- The term autotrophic (from the Greek autos, self, and trophos, feed) may seem to contradict the
principle that organisms are open systems, taking in resources from their environment

- For this reason, biologists refer to autotrophs as the producers of the biosphere (the global
ecosystem).

- Plants are autotrophs; the only nutrients they require are CO2 from the air, and H2O and minerals
from the soil.

- Specifically, plants are photo autotrophs, organisms that use light as a source of energy to
synthesize organic substances. Photosynthesis also occurs in algae, including certain protists, and
in some prokaryotes.

- Heterotrophs obtain their organic material by the second major mode of nutrition.

- Unable to make their own food, they live on compounds produced by other organisms;
heterotrophs are the biosphere’s consumers.

- The most obvious form of this "other-feeding" (hetero means "other, different") occurs when an
animal eats plants or other animals
 (Fern) algae
(a) (b)

(c) (e)

Protist cyanobacteria (d) Sulfur bacteria

Fig 2.19. Photoautotrophs.
These organisms use light energy to drive the synthesis of organic molecules from carbon dioxide and (in
most cases) water. They feed not only themselves, but the entire living world. (a) On land, plants are the
predominant producers of food. Three major groups of land plants--mosses, ferns, and flowering plants--
are represented in this scene. In oceans, ponds, lakes, and other aquatic environments, photosynthetic
organisms include (b) multicellular algae, such as this kelp; (c) some unicellular protists, such as
Euglena; (d) the prokaryotes called cyanobacteria; and (e) other photosynthetic prokaryotes, such as
these purple sulfur bacteria (c, d, e: LMs).
 Chloroplasts are the sites of photosynthesis in plants

- The leaves are the major sites of photosynthesis in most plants (fig10-2).

- The color of the leaf is from chlorophyll, the green pigment located within the chloroplasts.

- Chlorophyll resides in the thylakoid membranes

- Chlorophyll absorbs the light energy and drives the synthesis of food molecules in the
chloroplast.

- Chloroplasts are found mainly in the cells of the mesophyll, the tissue in the interior of the leaf.

- CO2 enters and O2 exits the leaf, by way of microscopic pores called stomata (singular, stoma;
from the Greek, meaning "mouth").

- H2O absorbed by the roots is delivered to the leaves in veins.

- Leaves also use veins to export sugar to roots and other nonphotosynthetic parts of the plant.
 Fig 2.20. 
Focusing in on the location of
photosynthesis in a plant.
Leaves are the major organs of
photosynthesis in plants. These
pictures take you into a leaf, then
into a cell, and finally into a
chloroplast, the organelle where
photosynthesis occurs. Gas
exchange between the leaf’s
mesophyll tissue and the
atmosphere occurs through
microscopic pores called stomata.
Chloroplasts, found mainly in the
mesophyll, are bounded by two
membranes that enclose the
stroma, a dense fluid. Membranes
of the thylakoid system separate
the stroma from the thylakoid
space. Thylakoids are
concentrated in stacks called
grana. (Middle right, LM; bottom
right, TEM.)
 THE PATHWAYS OF PHOTOSYNTHESIS

* Evidence that chloroplasts split water molecules enabled researchers to track atoms
through photosynthesis
* The light reactions and the Calvin cycle cooperate in converting light energy to the
chemical energy of food: an overview
* The light reactions convert solar energy to the chemical energy of ATP and NADPH: a
closer look
* The Calvin cycle uses ATP and NADPH to convert CO 2 to sugar: a closer look
* Alternative mechanisms of carbon fixation have evolved in hot, arid climates
* Photosynthesis is the biosphere’s metabolic foundation: a review
 Evidence that chloroplasts split water molecules
enabled researchers to track atoms through photosynthesis

2.1.1. The splitting of water

Exp 1: CO2 + 2H2O  CH2O + H2O + O2

Exp 2: CO2 + 2H2O  CH2O + H2O + O2

The most important result of the shuffling of atoms during photosynthesis is the extraction of H2
from H2O and its incorporation into sugar.

The waste product of photosynthesis, O2, restores the atmospheric O2 consumed during cellular
respiration. Fig10-3 shows the fates of all atoms in photosynthesis.

2.1.2. Photosynthesis as a redox process

- Photosynthesis, also a redox process, reverses the direction of electron flow.

- H2O is split, and electrons are transferred along with H+ from the H2O to CO2, reducing it to
sugar.
- The electrons increase in potential energy as they move from H2O to sugar.
- The required energy boost is provided by light

sugar
 Light energy

Fig 2.21. Tracking atoms through photosynthesis

 The light reactions and the Calvin cycle
cooperate in converting light energy to the chemical energy of food:
an overview

- These two stages of photosynthesis are known as the light reactions (the photo part of
photosynthesis) and the Calvin cycle (the synthesis part) (fig10-4).

2.2.1. Light reaction

- The light reactions are processed in chlorophyll

- The light reactions are the steps of photosynthesis that convert solar energy to chemical
energy

- Light absorbed by chlorophyll drives a transfer of electrons and H2 from H2O to an acceptor
called NADP+ (nicotinamide adenine dinucleotide phosphate), which temporarily stores the
energized electrons

- The light reactions also generate ATP by powering the addition of a phosphate group to ADP,
a process called photophosphorylation

- Thus, light energy is initially converted to chemical energy in the form of 2 compounds: NADPH
and ATP
 stroma

chlorophyll

Fig 2.22. An overview of photosynthesis:

cooperation of the light reactions and the Calvin cycle. In the chloroplast, the thylakoid
membranes are the sites of the light reactions, whereas the Calvin cycle occurs in the
stroma. The light reactions use solar energy to make ATP and NADPH, which function as
chemical energy and reducing power, respectively, in the Calvin cycle. The Calvin cycle
incorporates CO2 into organic molecules, which are converted to sugar. (Recall from
Chapter 5 that most simple sugars have formulas that are some multiple of CH2O.)
Calvin cycle

- The Calvin cycle is processed in stroma

- The cycle begins by incorporating CO2 from the air into organic molecules already present in the
chloroplast known as carbon fixation.

- The Calvin cycle reduces the fixed carbon to carbohydrate by the addition of electrons

- The reducing power is provided by NADPH, which acquired energized electrons in the light
reactions

- To convert CO2 to carbohydrate, the Calvin cycle also requires chemical energy in the form of
ATP, which is also generated by the light reactions.

- Thus, it is the Calvin cycle that makes sugar, with the help of the NADPH and ATP produced by the
light reactions

- The metabolic steps of the Calvin cycle are sometimes referred to as the dark reactions because
none of the steps requires light directly.

- The Calvin cycle in most plants occurs during daylight, for only then can the light reactions
regenerate the NADPH and ATP spent in the reduction of CO2 to sugar.

- Fig10-4 indicates, the thylakoids of the chloroplast are the sites of the light reactions, while the
Calvin cycle occurs in the stroma. As molecules of NADP+ and ADP bump into the thylakoid
membrane, they pick up electrons and phosphate, respectively, and then transfer their high-
energy cargo to the Calvin cycle.
 stroma

chlorophyll

Fig 2.23. An overview of photosynthesis:

cooperation of the light reactions and the Calvin cycle. In the chloroplast, the thylakoid
membranes are the sites of the light reactions, whereas the Calvin cycle occurs in the
stroma. The light reactions use solar energy to make ATP and NADPH, which function as
chemical energy and reducing power, respectively, in the Calvin cycle. The Calvin cycle
incorporates CO2 into organic molecules, which are converted to sugar. (Recall from
Chapter 5 that most simple sugars have formulas that are some multiple of CH2O.)
 The light reactions convert solar energy
to the chemical energy of ATP and NADPH: a closer look

- Chloroplasts are chemical factories powered by the sun. Their thylakoids transform light energy
into the chemical energy of ATP and NADPH

2.3.1. The nature of sunlight

- Light is a form of energy known as electromagnetic energy

- Electromagnetic waves are disturbances of electrical and magnetic fields

- The distance between the crests of electromagnetic waves is called the wavelength. Wavelengths
range from less than a nanometer (for gamma rays) to more than a kilometer (for radio waves).

- This entire range of radiation is known as the electromagnetic spectrum (fig2.24). The segment most
important to life is the narrow band that ranges from about 380 - 750 nm in wavelength.

- This radiation is known as visible light, because it is detected as various colors by the human eye.

- The model of light as waves explains many of light’s properties. It consists of photons. Photons
has a fixed quantity of energy.

- The amount of energy is inversely related to the wavelength of the light; the shorter the
wavelength, the greater the energy of each photon of that light. Thus, a photon of violet light packs
nearly twice as much energy as a photon of red light
 Fig 2.24. The electromagnetic spectrum.
Visible light and other forms of electromagnetic energy radiate through space as waves of
various lengths. We perceive different wavelengths of visible light, which range from about
380 to 750 nm, as different colors. White light is a mixture of all wavelengths of visible
light. A prism can sort white light into its component colors by bending light of different
wavelengths at different angles. Visible light drives photosynthesis
Photosynthetic pigments: The light receptors

- As light meets matter, it may be reflected, transmitted, or absorbed.

- Substances that absorb visible light are called pigments.

- Different pigments absorb light of different wavelengths, and the wavelengths that are
absorbed disappear.

- If a pigment is illuminated with white light, the color we see is the color most reflected or
transmitted by the pigment. (If a pigment absorbs all wavelengths, it appears black.)

- We see green when we look at a leaf because chlorophyll absorbs (red + blue light) while
transmitting and reflecting green light (fig2.26).

- The ability of a pigment to absorb various wavelengths of light can be measured with an
instrument called a spectrophotometer.

- This machine directs beams of light of different wavelengths through a solution of the pigment
and measures the fraction of the light transmitted at each wavelength. A graph plotting a
pigment’s light absorption (the fraction not transmitted or reflected) versus wavelength is called an
absorption spectrum
 chlorophyll

stroma

Fig 2.25. Why leaves are green: interaction of light with chloroplasts.

The pigment molecules of chloroplasts absorb blue and red light and reflect or transmit
green light. This is why leaves appear green. It turns out that blue and red are the colors
of light most effective in photosynthesis
 Fig 2.26. Determining an absorption spectrum.
A spectrophotometer measures the relative amounts of light of different wavelengths absorbed and
transmitted by a pigment solution. Inside the spectrophotometer, white light is separated into colors
(wavelengths) by a prism. Then, one by one, the different colors of light are passed through the sample.
The transmitted light strikes a photoelectric tube, which converts the light energy to electricity, and the
electrical current is measured by a galvanometer. Each time the wavelength of light is changed, the meter
indicates the fraction of light transmitted through the sample (or, conversely, the fraction of light
absorbed). This figure shows the transmittance reading on the meter when (a) green light and then
(b) blue light are passed through a chlorophyll solution
- The absorption spectra of chloroplast pigments provide clues to the relative effectiveness of
different wavelengths for driving photosynthesis, since light can perform work in chloroplasts only
if it is absorbed

Chlorophyll a

- Fig12.27a shows the absorption spectra of chlorophyll a and some other pigments in the
chloroplast.

- If we look first at the absorption spectrum of chlorophyll a, it suggests that blue and red light work
best for photosynthesis, while green is the least effective color.

- This is confirmed by an action spectrum for photosynthesis, which profiles the relative performance
of the different wavelengths

- The action spectrum for photosynthesis was first demonstrated in 1883 in an elegant experiment
performed by the German botanist Thomas Engelmann, who used bacteria to measure rates of
photosynthesis in filamentous algae.

- Notice by comparing fig2.27a and 2.27b that the action spectrum for photosynthesis does not
exactly match the absorption spectrum of chlorophyll a.

Chlorophyll b

- Only chlorophyll a can participate directly in the light reactions, which convert solar energy to
chemical energy

- But other pigments, chlorophyll b, in the thylakoid membrane can absorb light and transfer the
energy to chlorophyll a, which then initiates the light reactions.
 Fig 2.27. 
Evidence that
chloroplast
pigments
participate in
photosynthesis:
absorption and
action spectra for
photosynthesis in
an alga.
 Fig 2.28. Location and structure of chlorophyll molecules in plants.
A plant’s chlorophyll molecules, along with accessory pigment molecules, are immersed in the
thylakoid membranes of chloroplasts, in association with protein (purple). Chlorophyll a, the pigment
that participates directly in the light reactions of photosynthesis, has a "head," called a porphyrin ring,
with a magnesium atom at its center. Attached to the porphyrin is a hydrocarbon tail, which interacts
with hydrophobic regions of proteins inside the thylakoid membrane. Chlorophyll b differs from
chlorophyll a only in one of the functional groups bonded to the porphyrin.
2.3.3. Excitation of chlorophyll by light

What exactly happens when chlorophyll and other pigments absorb photons?

- Light supplies the photons

- Photons are absorbed by clusters of pigment molecules embedded in the thylakoid membrane.

- The energy of an absorbed photon is converted to the potential energy of an electron raised
from the ground state to an excited state (UP-HILL).

- When pigments absorb light, their excited electrons drop back down to the ground-state orbital
in a billionth of a second, releasing their excess energy as heat (DOWN-HILL)

- The electron jumps to a state of greater energy, and as it falls back to ground state, a photon is
given off. This afterglow is called fluorescence.

- If a solution of chlorophyll isolated from chloroplasts is illuminated, it will fluoresce in the red
part of the spectrum and also give off heat .
 Fig 2.29. Location and structure of chlorophyll molecules in plants.
A plant’s chlorophyll molecules, along with accessory pigment molecules, are immersed in the
thylakoid membranes of chloroplasts, in association with protein (purple). Chlorophyll a, the pigment
that participates directly in the light reactions of photosynthesis, has a "head," called a porphyrin ring,
with a magnesium atom at its center. Attached to the porphyrin is a hydrocarbon tail, which interacts
with hydrophobic regions of proteins inside the thylakoid membrane. Chlorophyll b differs from
chlorophyll a only in one of the functional groups bonded to the porphyrin.
 Fig 2.30. Excitation of isolated chlorophyll by light.
(a) Absorption of a photon causes a transition of the chlorophyll molecule from its ground state to its
excited state. The photon boosts an electron to an orbital where it has more potential energy. If the
illuminated molecule exists in isolation, its excited electron immediately drops back down to the ground-
state orbital, and its excess energy is given off as heat and fluorescence (light).
(b) A chlorophyll solution excited with ultraviolet light will fluoresce with a red-orange glow.
Photosynthesis: Light-harvesting complex of the thylakoid membrane

- A photosystem has a light-gathering "antenna complex" consisting of a cluster of a few hundred

chlorophyll a, chlorophyll b, and carotenoid molecules (fig2.31).

- Only chlorophyll a is located in the region of the photosystem called the reaction center, where
the first light-driven chemical reaction of photosynthesis occurs.

- The reaction center with the chlorophyll a is the primary electron acceptor

- The thylakoid membrane is populated by 2 types of photosystems that cooperate in the light
reactions of photosynthesis. They are called photosystem I and photosystem II.

- The reaction-center chlorophyll of photosystem I is known as P700 and the chlorophyll at the
reaction center of photosystem II is called P680

- These two pigments, P700 and P680, are actually identical chlorophyll a molecules.
 Chlorophyll a

chlorophyll a
Chlorophyll b
carotenoid

Fig 2.31. How a photosystem harvests light.

Photosystems are the light-harvesting units of the thylakoid membrane. Each photosystem is a complex
of proteins and other kinds of molecules and includes an antenna consisting of a few hundred pigment
molecules. When a photon strikes a pigment molecule, the energy is passed from molecule to molecule
until it reaches the reaction center. At the reaction center, an excited electron from the reaction-center
chlorophyll is captured by a specialized molecule called the primary electron acceptor
Noncyclic electron flow

How the two photosystems work together in using light energy to generate ATP and NADPH, the two
main products of the light reactions ?

- Light drives the synthesis of NADPH and ATP by energizing the 2 photosystems embedded in
the thylakoid membranes of chloroplasts.

- The key to this energy transformation is a flow of electrons through the photosystems and other
molecular components built into the thylakoid membrane.

- During the light reactions of photosynthesis, there are 2 possible routes for electron flow: cyclic
and noncyclic.

- Noncyclic electron flow, the predominant route

- The numbers in the text description correspond to the numbered steps in the figure.

- The energy changes of electrons as they flow through the light reactions are analogous to the
cartoon in fig10-13

- The light reactions use solar power to generate ATP and NADPH, which provide chemical
energy and reducing power, respectively, to the sugar-making reactions of the Calvin cycle.
 noncyclic electron flow

2e-
2e-

Fig 2.32. 
How noncyclic electron flow during the light reactions generates ATP and NADPH.
The gold arrows trace the current of light-driven electrons from water to NADPH. Each
photon of light excites a single electron, but the diagram tracks two electrons at a time,
the number of electrons required to reduce NADP+. The numbered steps are described in
the text.
 Fig 2.33. 
A mechanical
analogy for the
light reactions.
Cyclic electron flow

- Under certain conditions, photoexcited electrons take an alternative path called cyclic electron
flow, which uses photosystem I but not photosystem II.

- You can see in fig2.34 that cyclic flow is a short circuit: The electrons cycle back from ferredoxin
(Fd) to the cytochrome complex and from 3 continue on to the P700 chlorophyll. There is no
production of NADPH and no release of oxygen.

- Cyclic flow does generate ATP. This is called cyclic photophosphorylation, to distinguish it from
noncyclic photophosphorylation.

What is the function of cyclic electron flow?

- Noncyclic electron flow produces ATP and NADPH in roughly equal quantities, but the Calvin
cycle consumes more ATP than NADPH.

- Cyclic electron flow makes up the difference. The concentration of NADPH in the chloroplast
may help regulate which pathway, cyclic versus noncyclic, electrons take through the light
reactions.

- If the chloroplast runs low on ATP for the Calvin cycle, NADPH will begin to accumulate as the
Calvin cycle slows down.

- The rise in NADPH may stimulate a temporary shift from noncyclic to cyclic electron flow until
ATP supply catches up with demand
 Cyclic electron flow

ferredoxin
2e-

plastocyanin

Fig 2.34. Cyclic electron flow.

Photoexcited electrons from photosystem I are occasionally shunted back from ferredoxin
(Fd) to chlorophyll via the cytochrome complex and plastocyanin (Pc). This electron shunt
supplements the supply of ATP but produces no NADPH. The "shadow" of noncyclic electron
flow is included in the diagram for comparison with the cyclic route. The two ferredoxin
molecules shown in this diagram are actually one and the same--the final electron carrier in
the electron transport chain of photosystem I .
2.3.7. A comparision of chemiosmosis in chloroplst and mitochondria

The similar of 2 organelles

- Chloroplasts and mitochondria generate ATP by the same basic mechanism: chemiosmosis

- An electron transport chain assembled in a membrane pumps protons across the membrane as
electrons are passed through a series of carriers that are progressively more electronegative.

- Potential energy stored in the form of an H+ gradient across a membrane.

- Built into the same membrane is an ATP synthase complex that couples the diffusion of H+ down
their gradient to the phosphorylation of ADP.

- Some of the electron carriers are cytochromes (similar in chloroplasts and mitochondria).

- The ATP synthase complexes of the two organelles are also very much alike

- Chloroplasts do not need food to make ATP; their photosystems capture light energy and use it to
drive electrons to the top of the transport chain

- Mitochondria transfer chemical energy from food molecules to ATP, whereas chloroplasts
transform light energy into chemical energy
The difference between 2 organelles

- The spatial organization of chemiosmosis also differs in chloroplasts and mitochondria (fig2.35).

- The inner membrane of the mitochondrion pumps protons from the mitochondrial matrix out to the
intermembrane space, which then serves as a reservoir of H+ that powers the ATP synthase

- The thylakoid membrane of the chloroplast pumps protons from the stroma into the thylakoid
space, which functions as the H+ reservoir. The thylakoid membrane makes ATP as the H+ diffuse
from the thylakoid space back to the stroma through ATP synthase complexes, whose catalytic knobs
are on the stroma side of the membrane. Thus, ATP forms in the stroma, where it is used to help drive
sugar synthesis during the Calvin cycle.

- Fig2.36 shows a current model for the organization of the light-reaction "machinery" within the
thylakoid membrane. Each of the molecules and molecular complexes in the figure is present in
numerous copies in each thylakoid.

Notice that NADPH, like ATP, is produced on the side of the membrane facing the stroma, where the
Calvin cycle reactions take place.
 light

food

Fig 2.35. Comparison of chemiosmosis in mitochondria and chloroplasts.

In both kinds of organelles, electron transport chains pump protons (H+) across a membrane from a
region of low H+ concentration (light brown in this diagram) to one of high H+ concentration (darker
brown). The protons then diffuse back across the membrane through ATP synthase, driving the
synthesis of ATP. The diagram identifies the regions of high and low H+ concentration in the two
 Fig 2.36. The light reactions and chemiosmosis:
the organization of the thylakoid membrane. This diagram shows a current model for the
organization of the thylakoid membrane. The gold arrows track the noncyclic electron flow
outlined in fig10-12. As electrons pass from carrier to carrier in redox reactions, hydrogen
ions removed from the stroma are deposited in the thylakoid space, storing energy as a
proton-motive force (H+ gradient). At least three steps in the light reactions contribute to
the proton gradient: (1)   Water is split by photosystem II on the side of the membrane
facing the thylakoid space; (2) as plastoquinone (Pq), a mobile carrier, transfers electrons
to the cytochrome complex, protons are translocated across the membrane; and (3) a
hydrogen ion is removed from the stroma when it is taken up by NADP+. The diffusion of
H+ from the thylakoid space to the stroma (along the H+ concentration gradient) powers
the ATP synthase. These light-driven reactions store chemical energy in NADPH and ATP,
which shuttle the energy to the sugar-producing Calvin cycle
 The Calvin cycle uses ATP and NADPH
to convert CO2 to sugar: a closer look

- Carbon enters the Calvin cycle in the form of CO2 and leaves in the form of sugar. The cycle
spends ATP as an energy source and consumes NADPH as reducing power for adding high-
energy electrons to make the sugar

Fig10-17 divides the Calvin cycle into three phases :

Phase 1: Carbon fixation

RuBP carboxylase
3 CO2 + 1 RuBP -------------------- 6 (3-phosphate glycerate )

Phase 2: Reduction
6 (3-phospho glycerate) + 6ATP  6 (1,3-biphosphate glycerate) + 6 NADPH  6 G3P
(glycealdehyde-3-phosphate) + 6NAD+ + 6Pi  1 G3P is out put

Phase 3: Regeneration of CO2 acceptor (RuBP)

5 G3P + 3ATP  3 RuBP (ribulose biphosphate) + 3ADP

Net
3 CO2 + 1 RuBP + 9 ATP + 6 NADH  1 G3P
The light reactions regenerate the ATP and NADPH
 carboxylation reduction

(3) (6)

(6)
regeneration

(5) export
(6)

(1)

Fig 2.37. The Calvin cycle.

This diagram tracks carbon atoms (gray balls) through the cycle. The three phases of the cycle
correspond to the phases discussed in the text. For every three molecules of CO2 that enter the cycle,
the net output is one molecule of glyceraldehyde-3-phosphate (G3P), a three-carbon sugar. For each
G3P synthesized, the cycle spends nine molecules of ATP and six molecules of NADPH. The light
reactions sustain the Calvin cycle by regenerating ATP and NADPH
 Photosynthesis is the biosphere’s metabolic foundation: a review

Fig 2.38. A review of photosynthesis.

This diagram outlines the main reactants and products of the light reactions and the Calvin cycle as they
occur in the chloroplasts of plant cells. The entire ordered operation depends on the structural integrity
of the chloroplast and its membranes. Enzymes in the chloroplast and cytosol convert glyceraldehyde-3-
phosphate (G3P), the direct product of the Calvin cycle, into many other organic compounds
 CELL COMMUNICATION
  
  
  
AN OVERVIEW OF CELL SIGNALING
- Cell signaling evolved early in the history of life
- Communicating cells may be close together or far apart
- The three stages of cell signaling are reception, transduction, and response

SIGNAL RECEPTION AND THE INITIATION OF TRANSDUCTION

- A signal molecule binds to a receptor protein, causing the protein to change shape
- Most signal receptors are plasma membrane proteins

SIGNAL-TRANSDUCTION PATHWAYS
- Pathways relay signals from receptors to cellular responses
- Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of signal
transduction
- Certain small molecules and ions are key components of signaling pathways (second
messengers)

CELLULAR RESPONSES TO SIGNALS

- In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the
nucleus
- Elaborate pathways amplify and specify the cell’s response to signals
 AN OVERVIEW OF CELL SIGNALING

* Cell signaling evolved early in the history of life

* Communicating cells may be close together or far apart
* The three stages of cell signaling are reception, transduction, and response

What do cells talk about?

What kinds of things does a "talking" cell say to a "listening" cell, and how does the latter cell respond
to the message?
Let’s approach these questions by first looking at communication among microorganisms, for modern
microbes are a window to the role of cell signaling in the evolution of life on Earth
 Cell signaling evolved early in the history of life

- Researchers have learned that cells of this yeast identify their mates by chemical signaling
(fig11-1).

- There are 2 sexes, or mating types, called a and a.

- Cells of mating type a secrete a chemical signal called a factor, which can bind to specific
receptor proteins on nearby a cells.

- At the same time, a cells secrete a factor, which binds to receptors on a cells.

- The receptor-bound molecules of the 2 mating factors cause the cells to grow toward each
other and bring about other cellular changes.

- The result is the fusion, or mating, of 2 cells of opposite type.

- The new a /α cell contains all the genes of both original cells, a combination of genetic
resources that provides advantages to this cell’s descendants.

- How is the mating signal at the yeast cell surface transduced, or changed, into a form that brings
about the cellular response of mating? The process by which a signal on a cell’s surface is
converted into a specific cellular response is a series of steps called a signal-transduction
pathway.

- Scientists think that signaling mechanisms evolved first in ancient prokaryotes and single-
celled eukaryotes and were then adopted for new uses by their multicellular descendants
(fig11-2)
 2.39. 
Communication between
mating yeast cells.
Cells of the yeast
Saccharomyces cerevisiae
use chemical signaling to
identify cells of opposite
mating type and initiate the
mating process. The two
mating types and their
corresponding chemical
signals, or "mating factors,"
are called a and a. The
mating factors are peptides
about 12 amino acids in
length
 Fig 2.40. Communication among bacteria.
Soil-dwelling bacteria called myxobacteria ("slime bacteria") use chemical signaling to share
information about nutrient availability. When food is scarce, starving cells secrete a
molecule that enters neighboring cells and stimulates them to aggregate. The cells form a
structure that produces thick-walled spores capable of surviving until the environment
improves. The bacteria shown here are Myxococcus xanthus
 Communicating cells may be close together or far apart

- Like microbes, cells in a multicellular organism usually communicate by releasing chemical

messengers (chemical signaling) targeted for cells that may not be immediately adjacent.

- Some messengers travel only short distances: The transmitting cell secretes molecules of a
local regulator, a substance that influences cells in the vicinity . This type of local signaling in
animals is called paracrine signaling

- In the animal nervous system. Here a nerve cell produces a chemical signal, a neurotransmitter,
that diffuses to a single target cell that is almost touching the first cell

- Local signaling in plants is not as well understood

- Both animals and plants use chemicals called hormones for signaling at greater distances (fig11-
3b)

- Both animals and plants have cell junctions that directly connect the cytoplasms of adjacent cells .
In these cases, signaling substances dissolved in the cytosol can pass freely between adjacent
cells. Moreover, animal cells may communicate via direct contact between molecules on their
surfaces.

- This sort of signaling is important in embryonic development and in the operation of the immune
system

- What happens when a cell encounters a signal? The signal must be recognized by a specific
receptor molecule, and the information it carries must be changed into another form--transduced--
inside the cell before the cell can respond
 Fig 2.41. Local and long-distance cell communication in animals.
In both local and long-distance signaling, only specific target cells recognize and respond to
a given chemical signal
Fig 2.42. Communication by direct contact between cells
 The three stages of cell signaling
are reception, transduction, and response

- Sutherland’s early work suggested that the process going on at the receiving end of a cellular
conversation can be dissected into 3 stages: reception, transduction, and response:

(1) Reception. Reception is the target cell’s detection of a signal coming from outside the cell. A
chemical signal is "detected" when it binds to a cellular protein (receptor protein), usually at the
cell’s surface

(2) Transduction. The binding of the signal molecule changes the receptor protein in some way,
initiating the process of transduction. Transduction sometimes occurs in a single step but more
often requires a sequence of changes in a signal-transduction pathway. The molecules in the
pathway are often called relay molecules

(3) Response. In the third stage of cell signaling, the transduced signal finally triggers a specific
cellular response. The response may be almost any imaginable cellular activity: such as catalysis by
an enzyme (for example, glycogen phosphorylase), rearrangement of the cytoskeleton, or
activation of specific genes in the nucleus.
 Fig 2.43. Overview of cell signaling.
From the perspective of the cell receiving the message, cell signaling can be divided into
three stages: signal reception, signal transduction, and cellular response. When reception
occurs at the plasma membrane, as shown here, the transduction stage is usually a pathway
of several steps, with each molecule in the pathway bringing about a change in the next. The
last molecule in the pathway triggers the cell’s response. The three stages are explained in
the text
 SIGNAL RECEPTION AND THE INITIATION OF TRANSDUCTION

* A signal molecule binds to a receptor protein, causing the protein to change shape
* Most signal receptors are plasma membrane proteins

When we speak to someone, others nearby may hear our message, sometimes with unfortunate
consequences. However, errors of this kind rarely occur among cells. The signals emitted by an a
yeast cell are "heard" only by its prospective mates, a cells. Similarly, although epinephrine
encounters many types of cells as it circulates in the blood, only certain target cells detect and react
to the hormone. The signal receptor is the identity tag on the target cell
 A signal molecule binds to a receptor protein,
causing the protein to change shape

- A cell targeted by a particular chemical signal has molecules of a receptor protein that
recognize the signal molecule.

- The signal molecule is complementary in shape to a specific site on the receptor and
attaches there, like a substrate in the catalytic site of an enzyme.

- The signal molecule behaves as a ligand, the term for a small molecule that specifically
binds to a larger one.

- Ligand binding generally causes a receptor protein to undergo a change in conformation or

change shape
 Most signal receptors are plasma membrane proteins

- Most signal molecules are water-soluble and too large to pass freely through the plasma
membrane
- A receptor transmits information from the extracellular environment to the inside of the cell
by changing shape or aggregating when a specific ligand binds to it.
- How membrane receptors work by looking at three major types: G-protein-linked receptors,
tyrosine-kinase receptors, and ion-channel receptors

G-protein-linked receptors

- A G-protein-linked receptor = plasma membrane receptor + G protein  works .

- Many different signal molecules use G-protein-linked receptors, including yeast mating factors,
epinephrine and many other hormones, and neurotransmitters.

- These receptors vary in their binding sites for recognizing signal molecules and for
recognizing different G proteins inside the cell.

- Nevertheless, G-protein-linked receptor proteins are all remarkably similar in structure. They
each have seven a helices spanning the membrane, as shown in fig11-6.

- Loosely attached to the cytoplasmic side of the membrane, the G protein functions as a
switch that is on or off, depending on which of 2 guanine nucleotides is attached, GDP or GTP.
(GTP, or guanosine triphosphate, is similar to ATP.) As indicated in fig11-7 (p. 202), when GDP is
bound, the G protein is inactive; when GTP is bound, the G protein is active
 G protein + GDP  inactive
G protein + GTP  active

Fig 2.44. The structure of a G-protein-linked receptor.

A large family of eukaryotic receptor proteins have this secondary structure, where the
single polypeptide, represented as a ribbon, has seven transmembrane a helices. For
clarity, the a helices are depicted as cylinders and arranged in a straight line. Specific
loops correspond to the sites where signal molecules and G-protein molecules bind; the
loops labeled here are the binding sites in one particular case
Fig2.45b show the function how the
appropriate chemical signal activates the
entire G-protein system, When the signal
molecule binds as a ligand to the
extracellular side of a G-protein-linked
receptor
(1) The receptor is activated, changing
conformation, inactive G protein
(2) Causes a GTP to displace the GDP to
activate the G protein
(3) then, binds to an enzyme, and alters its
activity
(4) If the enzyme is activated, it can trigger
the next step in the pathway

(*) G protein also functions as a GTPase

enzyme and soon hydrolyzes its bound
GTP to GDP (fig11-7c)

Fig 2.45. 
The functioning of a G-protein-
linked receptor.
This type of receptor is a membrane
protein that works in conjunction with
a G protein and another protein,
usually an enzyme
Tyrosine-kinase receptors

- The receptor for a growth factor is often a tyrosine-kinase receptor, one of a major class of
plasma membrane receptors characterized by having enzymatic activity.
- Part of the receptor protein on the cytoplasmic side of the membrane functions as an enzyme,
called tyrosine kinase, that catalyzes the transfer of P groups from ATP to the amino acid
tyrosine on a substrate protein.
- Thus tyrosine-kinase receptors = membrane receptors + attach P to tyrosines.

- Many tyrosine-kinase receptors have the structure roughly

- Before the signal molecule binds, the receptors exist as individual polypeptides.
- Each has an extracellular signal-binding site, a single a helix spanning the membrane, and an
intracellular tail containing a number of tyrosines. The binding of a signal molecule to such a
receptor does not cause enough of a conformational change to activate the cytoplasmic side of
the protein directly

Fig2.46b, receptor activation occurs in 2 steps:  

(1) The ligand binding causes 2 receptor polypeptides to aggregate, forming a dimer (a protein
consisting of two polypeptides)
(2) This aggregation activates the tyrosine-kinase parts of both polypeptides, each of which
then adds P to the tyrosines on the tail of the other polypeptide.
(*) In summary, the effect of the signal molecule on a tyrosine-kinase receptor is polypeptide
aggregation and phosphorylation of the receptor
(3) Receptor protein is recognized by specific relay proteins inside the cell and binds to a specific
phosphorylated tyrosine that activates it (the relay protein may or may not be phosphorylated by
the tyrosine kinase).
(4) triggering as many different transduction pathways and cellular responses.
 helix

dimer

Fig 2.46. The structure and function of a tyrosine-kinase receptor

Ion chanel receptors

- Some membrane receptors of chemical signals are ligand-gated ion channels.

- These channels are protein pores in the plasma membrane that open or close in response to a
chemical signal, allowing or blocking the flow of specific ions, such as Na+ or Ca2+.

- These channel proteins bind a signal molecule as a ligand at a specific site on their extracellular
side (fig11-9)
 Fig 2.47. 
A ligand-gated ion-
channel receptor.
This receptor is a
transmembrane protein in
the plasma membrane
that opens to allow the
flow of a specific kind of
ion across the membrane
when a specific signal
molecule binds to the
extracellular side of the
protein
Intracellular receptors

- Not all signal receptors are membrane proteins

- Some are proteins dissolved in the cytosol or nucleus of target cells.

- To reach such a receptor, a chemical messenger (chemical signaling) must be able to pass through
the target cell’s plasma membrane

- Hydrophobic chemical messengers include the steroid hormones and thyroid hormones of animals.

- Another chemical signal with an intracellular receptor is NO (nitric oxide), a gas; its very small
molecules readily pass between the membrane phospholipids.

- How does the activated hormone-receptor protein turn on genes? Recall that the genes in a cell’s
DNA function by being transcribed into an messenger RNA (mRNA), which leaves the nucleus and is
translated into a specific protein by ribosomes in the cytoplasm
 Fig 2.48. 
Steroid hormone
interacting with an
intracellular receptor
 SIGNAL-TRANSDUCTION PATHWAYS

* Pathways relay signals from receptors to cellular responses

* Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of
signal transduction
* Certain small molecules and ions are key components of signaling pathways (second
messengers)

When signal receptors are plasma membrane proteins, like most of those we have discussed, the
transduction stage of cell signaling is usually a multistep pathway. One benefit of such pathways is
the possibility of greatly amplifying a signal. If some of the molecules in a pathway transmit the signal
to multiple molecules of the next component in the series, the result can be a large number of
activated molecules at the end of the pathway. In other words, a small number of extracellular signal
molecules can produce a large cellular response. Moreover, multistep pathways provide more
opportunities for coordination and regulation than simpler systems do, as we’ll discuss later
 Pathways relay signals from receptors to cellular responses

- The binding of a specific signal molecule to a receptor in the plasma membrane triggers the
first step in the chain of molecular interactions called the signal-transduction pathway

- The signal-transduction pathway leads to a particular response within the cell

- Like falling dominoes, the signal-activated receptor activates another protein, which activates
another molecule, and so on, until the protein that produces the final cellular response is
activated.

- The molecules that relay a signal from receptor to response, called relay molecules, are mostly
proteins. The interaction of proteins is a major theme of cell signaling

- When we say that the signal is relayed along a pathway, we mean that certain information is
passed on.

- At each step the signal is transduced into a different conformational change in a protein.

- Very often, the conformational change is brought about by phosphorylation.

 Protein phosphorylation, a common mode of regulation in cells,
is a major mechanism of signal transduction

- Many of the relay molecules in signal-transduction pathways are protein kinases, and they often
act on each other.

- Fig 2.49 depicts a hypothetical pathway containing 3 different protein kinases, which create a
"phosphorylation cascade."

- The signal is transmitted by a cascade of protein phosphorylations, each bringing with it a

conformational change.

- Each shape change results from the interaction of the charged P groups with charged or polar
amino acids .

- The addition of P often changes a protein from an inactive form to an active form (although in
other cases phosphorylation decreases the activity of the protein).

- The importance of protein kinases can hardly be overstated

- For a cell to respond normally to an extracellular signal, it must have mechanisms for turning off
the signal-transduction pathway when the initial signal is no longer present
Fig 2.49. A phosphorylation cascade.

In a phosphorylation cascade, a series of different molecules in a pathway are

phosphorylated in turn, each molecule adding a phosphate group to the next one in
line. The phosphorylation cascade shown here begins after a relay molecule
activates an enzyme we call protein kinase 1.

(1) Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule
of protein kinase 2, thus activating this second kinase.

(2) Active protein kinase 2 then catalyzes the phosphorylation (and activation) of
protein kinase 3.

(3) Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about
the cell’s response to the signal.

The dashed arrows represent inactivation of the phosphorylated proteins; enzymes

called phosphatases catalyze the removal of the phosphate groups from the
proteins, making them available for reuse. The active and inactive proteins are
represented by different shapes to remind you that activation is usually associated
with a change in molecular conformation.
 Plasma membrane

Cytosol
 Certain small molecules and ions
are key components of signaling pathways (second messengers)

- The extracellular signal molecule that binds to the membrane receptor is a pathway’s "first
messenger."
- Not all components of signal-transduction pathways are proteins.
- Many signaling pathways also involve small, nonprotein, water-soluble molecules or ions,
called second messengers.
- Because second messengers are both small and water-soluble, they can readily spread
throughout the cell by diffusion

Cycling AMP

- Sutherland found that the binding of epinephrine to the plasma membrane of a liver cell
elevates the cytosolic concentration of a compound called cyclic adenosine monophosphate,
abbreviated cyclic AMP or cAMP .

- An enzyme built into the plasma membrane, adenylyl cyclase, converts ATP to cAMP in response
to an extracellular signal, epinephrine.

- Adenylyl cyclase becomes active only after epinephrine binds to a specific receptor protein

- Thus, the first messenger, the hormone, causes a membrane enzyme to make cAMP, which
broadcasts the signal to the cytoplasm.
 Fig 2.50. Cyclic AMP.
Cyclic AMP (cAMP) is made from ATP by adenylyl cyclase, an enzyme embedded in the
plasma membrane. Cyclic AMP functions as a second messenger that can relay a signal
from the membrane to the metabolic machinery of the cytoplasm. Cyclic AMP is inactivated
by phosphodiesterase, an enzyme that converts it to AMP
- Epinephrine is only one of many hormones and other signal molecules that trigger the
formation of cAMP.

- It also brought to light the other components of cAMP pathways, including G proteins, G-
protein-linked receptors, and protein kinases

- The immediate effect of cAMP is usually the activation of a serine/ threonine kinase called
protein kinase A.

- The activated kinase then phosphorylates various other proteins, depending on the cell. (The
complete pathway for epinephrine’s stimulation of glycogen breakdown is shown later)
 Fig 2.51. cAMP as a second messenger.
Cyclic AMP is a component of many G-protein-signaling pathways. The signal molecule-- the
"first messenger"--activates a G-protein-linked receptor, which activates a specific G protein.
In turn, the G protein activates adenylyl cyclase, which catalyzes the conversion of ATP to
cAMP. The cAMP then activates another protein, usually protein kinase A.
 Fig 12.52. Cytoplasmic response to a signal:
the stimulation of glycogen breakdown by epinephrine. (a) In this signaling system, the hormone
epinephrine acts through a G-protein-linked receptor to activate a succession of relay molecules,
including cAMP and two protein kinases. The final protein to be activated is the cytosolic enzyme
glycogen phosphorylase, which releases glucose-1-phosphate units from glycogen. (b) As discussed in
the next section of the text, this pathway amplifies the hormonal signal, because the receptor protein can
activate many molecules of G protein, and each enzyme molecule in the pathway can act on many
molecules of its substrate, the next molecule in the cascade. The number of activated molecules given for
each step is only approximate
Ca2+ and Inositl phosphate

Animal cell
- Many signal molecules in animals, including neurotransmitters, growth factors, and some
hormones, induce responses in their target cells via signal-transduction pathways that
increase the cytosolic concentration of calcium ions (Ca2+).

- Ca2+ is even more widely used than cAMP as a second messenger.

- Increasing the cytosolic concentration of Ca2+ causes many responses in animal cells, including
muscle cell contraction, secretion of certain substances, and cell division.

Plant cell
- In plant cells, Ca2+ functions as a second messenger in signaling pathways plants have evolved
for coping with environmental stresses, such as drought or cold.
- Cells use Ca2+ as a second messenger in both G-protein pathways and tyrosine-kinase
pathways.

- Ca2+, can function as a second messenger because its concentration in the cytosol is normally
much lower than the concentration outside the cell.

- Ca2+ are actively transported out of the cell and are actively imported from the cytosol into the
endoplasmic reticulum ER (and, under some conditions, into mitochondria and chloroplasts) by
various protein pumps

- As a result, the Ca2+ concentration in the ER is usually much higher than in the cytosol

The pathways leading to Ca2+ release involve still other second messengers, diacylglycerol (DAG)
and inositol trisphosphate (IP3) .

- These 2 messengers are produced by cleavage of a certain kind of phospholipid in the plasma
membrane.

- Fig2.53 shows how this occurs and how IP3 stimulates the release of Ca2+ from the ER.

- Because IP3 acts before Ca2+ in these pathways, Ca2+ could be considered a "third messenger."

- However, scientists use the term second messenger for all small, nonprotein components of
signal-transduction pathways

- In some cases, Ca2+ activate a signal-transduction protein directly, but often they function by
means of calmodulin, a Ca2+-binding protein present at high levels in eukaryotic cells
 Fig 2.53. The maintenance of calcium ion concentrations in an animal cell.
The Ca2+ concentration in the cytosol is usually much lower (light blue) than in the
extracellular fluid and ER (darker blue). Protein pumps in the plasma membrane and the
ER membrane move Ca2+ from the cytosol into the extracellular fluid and into the lumen
of the ER. Mitochondrial pumps, driven by chemiosmosis (see Chapter 9), move Ca2+ into
mitochondria when the calcium level in the cytosol rises significantly
 Fig 2.54. Calcium and inositol trisphosphate in signaling pathways.
Calcium ions (Ca2+) and inositol trisphosphate (IP3) function as second messengers in
many signal-transduction pathways. The process is initiated by the binding of a signal
molecule to either a G-protein-linked receptor (left) or a tyrosine-kinase receptor (right). The
circled numbers trace the former pathway
 CELLULAR RESPONSES TO SIGNALS

* In response to a signal, a cell may regulate activities in the cytoplasm or transcription in
the nucleus
* Elaborate pathways amplify and specify the cell’s response to signals

We now take a closer look at the cell’s eventual response to an extracellular signal--what
some researchers call the "output response." What is the nature of the final step in a
signaling pathway?
 In response to a signal, a cell may regulate activities
in the cytoplasm or transcription in the nucleus

- A signal-transduction pathway leads to the regulation of one or more cellular activities.

- In the cytoplasm, a signal may cause the opening or closing of an ion channel in the plasma
membrane or a change in cell metabolism.
- The final step in the signaling pathway activates the enzyme that catalyzes the breakdown of
glycogen.
- Fig2.55 shows the complete pathway leading to the release of glucose-1-phosphate from
glycogen.

- The final activated molecule in a signaling pathway may function as a transcription factor

In figure 2.55

- A signaling pathway activates a transcription factor that turns a gene on: The response to the
growth-factor signal is the synthesis of mRNA that will be translated in the cytoplasm into a
specific protein.

- In other cases, the transcription factor might regulate a gene by turning it off. Often a
transcription factor regulates several different genes.

- All the different kinds of signal receptors and relay molecules participate in various gene-
regulating pathways, as well as in pathways leading to other kinds of responses

- Malfunctioning of growth-factor pathways like the one can cause cancer

 Fig 2.55. Cytoplasmic response to a signal:
the stimulation of glycogen breakdown by epinephrine. (a) In this signaling system, the hormone
epinephrine acts through a G-protein-linked receptor to activate a succession of relay molecules,
including cAMP and two protein kinases. The final protein to be activated is the cytosolic enzyme
glycogen phosphorylase, which releases glucose-1-phosphate units from glycogen. (b) As discussed in
the next section of the text, this pathway amplifies the hormonal signal, because the receptor protein can
activate many molecules of G protein, and each enzyme molecule in the pathway can act on many
molecules of its substrate, the next molecule in the cascade. The number of activated molecules given for
each step is only approximate
 Fig 2.56. 
Nuclear response to a signal: the
activation of a specific gene by a
growth factor.
This diagram is a simplified
representation of a typical signaling
pathway that leads to the regulation
of gene activity in the cell nucleus.
The initial signal molecule, a local
regulator called a growth factor,
triggers a phosphorylation cascade.
(The ATP molecules that serve as
sources of phosphate are not shown.)
The last kinase in the sequence
enters the nucleus and there
activates a gene-regulating protein, a
transcription factor. This protein
stimulates a specific gene to be
transcribed into mRNA, which then
directs the synthesis of a particular
protein in the cytoplasm.
 Elaborate pathways
amplify and specify the cell’s response to signals

Why are there often so many steps between a signaling event at the cell surface and the cell’s
response? Signaling pathways with a multiplicity of steps have 2 important benefits:
- They amplify the signal (and thus the response),
- and they contribute to the specificity of response.

Signal amplification

- Elaborate enzyme cascades amplify the cell’s response to a signal.

- At each catalytic step in the cascade, the number of activated products is much greater than in
the preceding step.

- For example, in the epinephrine-triggered pathway , each adenylyl cyclase molecule catalyzes
the formation of many cAMP molecules, each molecule of protein kinase A phosphorylates
many molecules of the next kinase in the pathway, and so on

- As a result of the signal’s amplification, a small number of epinephrine (molecules binding to

receptors on the surface of a liver cell or muscle cell) can lead to the release of hundreds of
millions of glucose molecules from glycogen.
 Fig 2.57. Cytoplasmic response to a signal:
the stimulation of glycogen breakdown by epinephrine. (a) In this signaling system, the hormone
epinephrine acts through a G-protein-linked receptor to activate a succession of relay molecules,
including cAMP and two protein kinases. The final protein to be activated is the cytosolic enzyme
glycogen phosphorylase, which releases glucose-1-phosphate units from glycogen. (b) As discussed in
the next section of the text, this pathway amplifies the hormonal signal, because the receptor protein can
activate many molecules of G protein, and each enzyme molecule in the pathway can act on many
molecules of its substrate, the next molecule in the cascade. The number of activated molecules given for
each step is only approximate
Specificity of cell signaling

- Consider two different cells in your body--a liver cell and a heart muscle cell
- Epinephrine stimulates the liver cell to break down glycogen, but the heart cell response to
epinephrine is contraction, leading to a more rapid heartbeat. How do we account for this
difference?

- The explanation for the specificity exhibited in cellular responses to signals is the same as the basic
explanation for virtually all differences between cells: Different kinds of cells have different
collections of proteins (fig2.58).

- Thus, 2 cells that respond differently to the same signal differ in one or more of the proteins that
handle and respond to the signal

Fig11-18 that different pathways may have some molecules in common.

- Cells A, B, and C all use the same receptor protein for the triangular signal molecule; differences in
other proteins account for their differing responses.
- In cell B, a pathway triggered by a single kind of signal diverges to produce two responses; such
branched pathways often involve tyrosine-kinase receptors (which can activate multiple relay proteins)
or second messengers (which can regulate numerous proteins).
- In cell C, two pathways triggered by separate signals converge to modulate a single response.
Branching of pathways and "cross-talk" (interaction) between pathways are important in regulating and
coordinating a cell’s responses to incoming information.
- Moreover, the use of some of the same proteins in more than one pathway allows the cell to
economize on the number of different proteins it must make.

The signaling pathways in fig2.58 are greatly simplified.

 Fig 2.58. The specificity of cell signaling.
The particular proteins a cell possesses determine what signal molecules it responds to and
the nature of the response. The four cells in these diagrams respond to the same signal
molecule (orange triangle) in different ways, because each has a different set of proteins
(purple and green shapes). Note, however, that the same kinds of molecules can participate
in more than one pathway
 How does a particular protein kinase, for instance, find its substrate?
- Recent research suggests that the efficiency of signal transduction may in many cases be
increased by the presence of scaffolding proteins, large relay proteins to which several other
relay proteins are simultaneously attached.
- For example, one scaffolding protein isolated from mouse brain cells holds 3 protein kinases
and carries these kinases with it when it binds to an appropriately activated membrane receptor; it
thus facilitates a specific phosphorylation cascade (fig2.59)

Fig 2.59. 
A scaffolding protein.
The scaffolding protein
shown here (pink)
simultaneously binds
to a specific activated
membrane receptor
and three different
protein kinases. This
physical arrangement
facilitates signal
transduction by these
molecules.
Thank you for your listening