1. An Introduction to Metabolism
Chapter 8
An Introduction to Metabolism

2. Metabolism is the totality of an organism’s chemical reactions
Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
Metabolism is the totality of an organism’s chemical reactions
Metabolism is an emergent property of life that arises from interactions between molecules within the cell
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3. Organization of the Chemistry of Life into Metabolic Pathways
A metabolic pathway begins with a specific molecule and ends with a product
Each step is catalyzed by a specific enzyme
Catabolic pathways release energy by breaking down complex molecules into simpler compounds
Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism
Anabolic pathways consume energy to build complex molecules from simpler ones
The synthesis of protein from amino acids and photosynthesis are examples of anabolism
Bioenergetics is the study of how organisms manage their energy resources
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting
molecule
Product

4. Forms of Energy
Kinetic Energy – energy of motion; heat (thermal energy) is kinetic energy associated with the random movement of atoms or molecules
Potential Energy – stored energy; the energy that matter possesses because of its location or structure
Chemical Energy – refers to the potential energy available for release in chemical reactions

5. A diver has more potential energy on the platform than in the water.
Fig. 8-2
A diver has more potential
energy on the platform
than in the water.
Diving converts
potential energy to
kinetic energy.
Figure 8.2 Transformations between potential and kinetic energy
Climbing up converts the kinetic
energy of muscle movement
to potential energy.
A diver has less potential
energy in the water
than on the platform.

6. Laws of Energy Transformation
Thermodynamics – Study of the energy transformations
First Law of Thermodynamics – The energy of the universe is constant. Energy/Matter can be transferred and transformed, but it cannot be created of destroyed
Second Law of Thermodynamics – Every energy transfer of transformation increases the entropy (disorder/randomness) of the universe. Ordered forms of energy are at least partly converted to heat.
CO2
H2O
Heat
Figure 8.3 The two laws of thermodynamics
CO2 +
H2O
Chemical
energy
(a) First law of thermodynamics
(b) Second law of thermodynamics

7. Biological Order and Disorder
Cells create ordered structures from less ordered materials
Organisms also replace ordered forms of matter and energy with less ordered forms
Energy flows into most ecosystems in the form of light and exits in the form of heat (Deep sea vents provide chemical energy in some marine ecosystems)
50 µm
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8. Fig. 8-5 More free energy (higher G) Less stable Greater work capacity
In a spontaneous change
The free energy of the system
decreases (∆G < 0)
The system becomes more
stable
The released free energy can
be harnessed to do work
Less free energy (lower G)
More stable
Less work capacity
Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change
(a) Gravitational motion – Objects
move spontaneously from a
higher altitude to a lower one
(b) Diffusion – Molecules
in a drop of dye diffuse
until the are randomly
dispersed
(c) Chemical reaction –
In a cell, a sugar
molecule is broken
down into simpler
molecules.

9. Amount of energy released (∆G < 0)
Fig. 8-6a
Reactants
Amount of
energy
released
(∆G < 0)
Free energy
Energy
Products
Figure 8.6a Free energy changes (ΔG) in exergonic and endergonic reactions
Progress of the reaction
Exergonic reaction: proceedes with a net release of free
energy and is spontaneous

10. Amount of energy required (∆G > 0)
Fig. 8-6b
Products
Amount of
energy
required
(∆G > 0)
Energy
Free energy
Reactants
Figure 8.6b Free energy changes (ΔG) in exergonic and endergonic reactions
Progress of the reaction
(b) Endergonic reaction: absorbs free energy from its
surrounding and is not spontaneous

11. An isolated hydroelectric system. Water flowing downhill turns
Fig. 8-7a
∆G < 0
∆G = 0
Figure 8.7a Equilibrium and work in isolated and open systems
An isolated hydroelectric system. Water flowing downhill turns
a turbines that drives a generator providing electricity to a light
bulb, but only until the system reaches equilibrium

12. (b) An open hydroelectric system – Flowing water keeps
Fig. 8-7b
∆G < 0
Figure 8.7b Equilibrium and work in isolated and open systems
(b) An open hydroelectric system – Flowing water keeps
driving the generator because intake and outflow of water
keep the system from reaching equilibrium.

13. (c) A multistep open hydroelectric system – Cellular respiration
Fig. 8-7c
∆G < 0
∆G < 0
∆G < 0
Figure 8.7c Equilibrium and work in isolated and open systems
(c) A multistep open hydroelectric system – Cellular respiration
is analogous to this system: Glucose is broken down in a series
of exergonic reactions that power the work of the cell. The
product of each reaction becomes the reactant for the next, so
no reaction reaches equilibrium.

14. Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions
A cell does three main kinds of work:
Chemical – The pushing of endergonic reactions, such as the building of polymers from monomers.
Transport – Active transport
Mechanical – Ex. – sister chromatides moving to opposite poles during cell division
To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one (energy released from a “downhill” reaction can be used to drive an “uphill” reaction
Most energy coupling in cells is mediated by ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP
In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction
Overall, the coupled reactions are exergonic
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15. Adenine Phosphate groups Ribose Fig. 8-8
Figure 8.8 The structure of adenosine triphosphate (ATP)
Ribose

16. H2O P P P Adenosine triphosphate (ATP) P + P P + Energy
Fig. 8-9 P P P
Adenosine triphosphate (ATP)
H2O
Figure 8.9 The hydrolysis of ATP P + P P +
Energy i
Inorganic phosphate
Adenosine diphosphate (ADP)

17. ∆G = +3.4 kcal/mol Glutamic acid Ammonia Glutamine
Fig. 8-10
NH2
NH3 +
∆G = +3.4 kcal/mol
Glu
Glu
Glutamic
acid
Ammonia
Glutamine
(a) Endergonic reaction 1
ATP phosphorylates
glutamic acid,
making the amino
acid less stable. P +
ATP +
ADP
Glu
Glu
NH2 P 2
Ammonia displaces
the phosphate group,
forming glutamine.
NH3 + + P i
Glu
Glu
Figure 8.10 How ATP drives chemical work: Energy coupling using ATP hydrolysis
(b) Coupled with ATP hydrolysis, an exergonic reaction
(c) Overall free-energy change

18. The recipient molecule is now phosphorylated
ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant
The recipient molecule is now phosphorylated
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19. Membrane protein Solute Solute transported Vesicle Cytoskeletal track
Fig. 8-11
Membrane protein
ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant or protein
The recipient molecule is now phosphorylated P P i
Solute
Solute transported
(a) Transport work: ATP phosphorylates
transport proteins
ADP
ATP + P i
Vesicle
Cytoskeletal track
Figure 8.11 How ATP drives transport and mechanical work
ATP
Motor protein
Protein moved
(b) Mechanical work: ATP binds noncovalently
to motor proteins, then is hydrolyzed

20. The Regeneration of ATP
Fig. 8-12
The Regeneration of ATP
ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
The energy to phosphorylate ADP comes from catabolic reactions in the cell
The chemical potential energy temporarily stored in ATP drives most cellular work
ATP
H2O +
Figure 8.12 The ATP cycle
Energy for cellular
work (endergonic,
energy-consuming
processes)
Energy from
catabolism (exergonic,
energy-releasing
processes) P
ADP + i

21. Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers
A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction
An enzyme is a catalytic protein
Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction
Enzymes catalyze reactions by lowering the EA barrier
Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually
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22. Sucrose (C12H22O11) Sucrase Glucose (C6H12O6) Fructose (C6H12O6)
Fig. 8-13
Sucrose (C12H22O11)
Sucrase
Figure 8.13 Example of an enzyme-catalyzed reaction: hydrolysis of sucrose by sucrase
Glucose (C6H12O6)
Fructose (C6H12O6)

23. Progress of the reaction
Fig. 8-14 A B C D
Transition state A B EA C D
Free energy
Reactants A B
Figure 8.14 Energy profile of an exergonic reaction
∆G < O C D
Products
Progress of the reaction

24. Progress of the reaction
Fig. 8-15
Course of
reaction
without
enzyme EA
without
enzyme
EA with
enzyme
is lower
Reactants
Free energy
Course of
reaction
with enzyme
∆G is unaffected
by enzyme
Figure 8.15 The effect of an enzyme on activation energy
Products
Progress of the reaction

25. The active site can lower an EA barrier by
Fig. 8-17
Substrates enter active site; enzyme
changes shape such that its active site
enfolds the substrates (induced fit). 1
Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds. 2
Substrates
Enzyme-substrate
complex
Active site can lower EA
and speed up a reaction. 3
Active
site is
available
for two new
substrate
molecules. 6
The active site can lower an EA barrier by
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
Figure 8.17 The active site and catalytic cycle of an enzyme
Enzyme 5
Products are
released.
Substrates are
converted to
products. 4
Products

26. Substrate Active site Enzyme-substrate Enzyme complex
Figure 8.16 Induced fit between an enzyme and its substrate
Enzyme-substrate
complex
Enzyme
The active site of the enzyme forms a groove on
its surface.
When the substrate enters the active site, it induces
a change in the shape of the protein, allowing
more weak bonds to form, causing the active site to
Enfold the substrate and hold it in place.

27. Optimal temperature for typical human enzyme Optimal temperature for
Fig. 8-18
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria
Each enzyme has an optimal temperature in which it can function
Each enzyme has an optimal pH in which it can function
Rate of reaction 20 40 60 80
100
Temperature (ºC)
(a) Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme)
Figure 8.18 Environmental factors affecting enzyme activity
Rate of reaction 1 2 3 4 5 6 7 8 9 10 pH
(b) Optimal pH for two enzymes

28. Cofactors Cofactors are nonprotein enzyme helpers
Cofactors may be inorganic (such as a metal in ionic form) or organic
An organic cofactor is called a coenzyme
Coenzymes include vitamins
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29. Enzyme Inhibitors Substrate Active site Competitive inhibitor Enzyme
Competitive inhibitors bind to the active site of an enzyme, competing with the substrate
Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective
Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
Substrate
Active site
Competitive
inhibitor
Figure 8.19 Inhibition of enzyme activity
Enzyme
Noncompetitive inhibitor
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition

30. Concept 8.5: Regulation of enzyme activity helps control metabolism
Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes
Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
Most allosterically regulated enzymes are made from polypeptide subunits
Each enzyme has active and inactive forms
The binding of an activator stabilizes the active form of the enzyme
The binding of an inhibitor stabilizes the inactive form of the enzyme
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31. Stabilized active form
Fig. 8-20a
Allosteric enzyme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Oscillation
Figure 8.20a Allosteric regulation of enzyme activity
Non-
functional
active
site
Inhibitor
Inactive form
Stabilized inactive
form
(a) Allosteric activators and inhibitors

32. (b) Cooperativity: another type of allosteric activation
Fig. 8-20b
Cooperativity is a form of allosteric regulation that can amplify enzyme activity
In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits
Substrate
Inactive form
Stabilized active
form
Figure 8.20b Allosteric regulation of enzyme activity
(b) Cooperativity: another type of allosteric activation

33. Feedback Inhibition
In feedback inhibition, the end product of a metabolic pathway shuts down the pathway
Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed
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34. Fig. 8-22 Initial substrate (threonine) Active site available
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Enzyme 2
Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off.
Intermediate B
Enzyme 3
Intermediate C
Figure 8.22 Feedback inhibition in isoleucine synthesis
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)

35. Specific Localization of Enzymes Within the Cell
Fig. 8-23
Mitochondria
Specific Localization of Enzymes Within the Cell
Structures within the cell help bring order to metabolic pathways
Some enzymes act as structural components of membranes
In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria
Figure 8.23 Organelles and structural order in metabolism
1 µm

36. You should now be able to:
Distinguish between the following pairs of terms: catabolic and anabolic pathways; kinetic and potential energy; open and closed systems; exergonic and endergonic reactions
In your own words, explain the second law of thermodynamics and explain why it is not violated by living organisms
Explain in general terms how cells obtain the energy to do cellular work
Explain how ATP performs cellular work
Explain why an investment of activation energy is necessary to initiate a spontaneous reaction
Describe the mechanisms by which enzymes lower activation energy
Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37. Progress of the reaction
Fig. 8-UN2
Course of
reaction
without
enzyme EA
without
enzyme
EA with
enzyme
is lower
Reactants
Free energy
Course of
reaction
with enzyme
∆G is unaffected
by enzyme
Products
Progress of the reaction

38. Fig. 8-UN3

39. Fig. 8-UN4

40. Fig. 8-UN5