Chapter 8 introduces metabolism as the totality of chemical reactions within living cells, highlighting the distinction between catabolic (energy-releasing) and anabolic (energy-consuming) pathways. It emphasizes the laws of thermodynamics, detailing energy transformations, and discusses the role of ATP as the energy currency of the cell, essential for driving various cellular processes. The chapter also explores enzyme function, including how they lower activation energy and regulate metabolic pathways to maintain cellular efficiency.

1. Chapter 8
An Introduction to Metabolism

2. Overview: The Energy of Life
• The living cell is a miniature chemical factory
where thousands of reactions occur
• The cell extracts energy and applies energy to
perform work
• Some organisms even convert energy to light,
as in bioluminescence
• 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

3. Enzyme 1
A B
Reaction 1
Enzyme 2
C
Reaction 2
Enzyme 3
D
Reaction 3
ProductStarting
molecule
•A metabolic pathway begins with a specific molecule and ends with a product
•Each step is catalyzed by a specific enzyme

4. •Catabolic pathways release energy by breaking
down complex molecules into simpler compounds

5. Anabolic pathways consume energy to build complex molecules
from simpler ones

6. Forms of Energy
• Energy is the capacity to cause change
• Energy exists in various forms, some of which
can perform work
• Bioenergetics is the study of how organisms
manage their energy resources

7. • Kinetic energy is energy associated with motion
– Heat (thermal energy) is kinetic energy associated with random
movement of atoms or molecules
• Potential energy is energy that matter possesses because
of its location or structure
– Chemical energy is potential energy available for release in a
chemical reaction
• Energy can be converted from one form to another
• Solar energy
– Light energy can be converted to chemical energy by
photosynthesis

8. On the platform,
the diver has
more potential
energy.
Diving converts
potential
energy to
kinetic energy.
Climbing up converts
kinetic energy of
muscle movement to
potential energy.
In the water, the
diver has less
potential energy.
Add solar, potential, &
chemical energy for this
picture.

9. The Laws of Energy
Transformation
• Thermodynamics is the study of energy
transformations
• A closed system, such as that approximated by
liquid in a thermos, is isolated from its
surroundings
• In an open system, energy and matter can be
transferred between the system and its
surroundings
• Organisms are open systems

10. The First Law of Thermodynamics
• According to the first law of thermodynamics, the energy of the
universe is constant
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
• The first law is also called the principle of conservation of energy
The Second Law of Thermodynamics
• During every energy transfer or transformation, some energy is
unusable, often lost as heat
• According to the second law of thermodynamics, every energy
transfer or transformation increases the entropy (disorder) of the
universe

11. Chemical
energy
Heat CO2
First law of thermodynamics Second law of thermodynamics
H2O
•Living cells unavoidably convert organized forms
of energy to heat
•Spontaneous processes occur without energy
input; they can happen quickly or slowly (very
slowly in order to get over EA)
•For a process to occur without energy input, it
must increase the entropy of the universe

12. 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
• The evolution of more complex organisms does
not violate the second law of thermodynamics
• Entropy (disorder) may decrease in an
organism, but the universe’s total entropy
increases

13. • The change in free energy (∆G) during a
process is related to the change in enthalpy, or
change in total energy (∆H), and change in
entropy (T∆S):
∆G = ∆H - T∆S
• Energy in reactions with a negative ∆G can be
harnessed to perform work
• A living system’s free energy is energy that
can do work when temperature and pressure
are uniform, as in a living cell

14. 1. The oxidation of glucose to CO2 and H2O
is highly exergonic: ∆G = −636 kcal/mole.
This is possible, but why is it very slow?
a. Few glucose and oxygen molecules have the
activation energy at room temperature.
b. There is too much CO2 in the air.
c. CO2 has higher energy than glucose.
d. The formation of six CO2 molecules from one
glucose molecule decreases entropy.
e. The water molecules quench the reaction.

15. 1. The oxidation of glucose to CO2 and H2O
is highly exergonic: ∆G = −636 kcal/mole.
This is possible, but why is it very slow?
a. Few glucose and oxygen molecules have
the activation energy at room temperature.
b. There is too much CO2 in the air.
c. CO2 has higher energy than glucose.
d. The formation of six CO2 molecules from one
glucose molecule decreases entropy.
e. The water molecules quench the reaction.

16. LE 8-5
Gravitational motion Diffusion Chemical reaction
More free energy

17. Change in Free Energy
• Free energy of the products – free energy
of reactants = negative, then products
have a greater stability than reactants
• Products have less free energy; in open
system, must include environment
• An exergonic reaction proceeds with a net
release of free energy
• An endergonic reaction absorbs free energy
from its surroundings and reactants are more
stable than products

18. LE 8-6a
Reactants
Energy
Products
Progress of the reaction
Amount of
energy
released
(∆G < 0)
Freeenergy
Exergonic reaction: energy released

19. LE 8-6b
Reactants
Energy
Products
Progress of the reaction
Amount of
energy
required
(∆G > 0)
Freeenergy
Endergonic reaction: energy required

20. 2. Firefly luciferase catalyzes the following reaction:
luciferin + ATP ↔ adenyl-luciferin + pyrophosphate
Then the next reaction occurs spontaneously:
adenyl-luciferin + O2 → oxyluciferin + H2O + CO2 + AMP + light
What is the role of luciferase?
a. Luciferase makes the ∆G of the reaction more
negative.
b. Luciferase produces a transition state with a
lower free energy
c. Luciferase alters the equilibrium point of the
reaction.
d. Luciferase makes the reaction irreversible.
e. Luciferase creates a phosphorylated
intermediate.

21. 2. Firefly luciferase catalyzes the following reaction:
luciferin + ATP ↔ adenyl-luciferin + pyrophosphate
Then the next reaction occurs spontaneously:
adenyl-luciferin + O2 → oxyluciferin + H2O + CO2 + AMP + light
What is the role of luciferase?
a. Luciferase makes the ∆G of the reaction more
negative.
b. Luciferase produces a transition state with a
lower free energy.
c. Luciferase alters the equilibrium point of the
reaction.
d. Luciferase makes the reaction irreversible.
e. Luciferase creates a phosphorylated
intermediate.

22. Equilibrium and Metabolism
• Reactions in a closed system eventually reach
equilibrium and then do no work
• Cells are not in equilibrium; they are open
systems experiencing a constant flow of
materials
• A catabolic pathway in a cell releases free
energy in a series of reactions
• Closed and open hydroelectric systems can
serve as analogies

23. LE 8-7a
∆G = 0
A closed hydroelectric system
∆G < 0

24. LE 8-7b
An open hydroelectric system
∆G < 0

25. LE 8-7c
A multistep open hydroelectric system
∆G < 0
∆G < 0
∆G < 0

26. Concept 8.3: ATP powers cellular
work by coupling exergonic
reactions to endergonic reactions
• A cell does three main kinds of work:
– Mechanical
– Transport
– Chemical
• To do work, cells manage energy resources by
energy coupling, the use of an exergonic
process to drive an endergonic one

27. Phosphate groups
Ribose
Adenine
ATP (adenosine triphosphate) is the cell’s
energy shuttle
ATP provides energy for cellular functions

28. • The bonds between the phosphate groups of
ATP’s tail can be broken by hydrolysis
• Energy is released from ATP when the terminal
phosphate bond is broken
• This release of energy comes from the
chemical change to a state of lower free
energy, not from the phosphate bonds
themselves

29. LE 8-9
Adenosine triphosphate (ATP)
Energy
P P P
PPP i
Adenosine diphosphate (ADP)Inorganic phosphate
H2O
+ +

30. • 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

31. LE 8-10
Endergonic reaction: ∆G is positive, reaction
Requires input of energy
Exergonic reaction: ∆G is negative, products have
less free energy than reactants
∆G = +3.4 kcal/mol
∆G = –7.3 kcal/mol
∆G = –3.9 kcal/mol
NH2
NH3
Glu Glu
Glutamic
acid
Coupled reactions: Overall ∆G is negative;
together, reactions give off heat
Ammonia Glutamine
ATP H2O ADP P i
+
+ +

32. How ATP Performs Work
• ATP drives endergonic reactions by
phosphorylation, transferring a phosphate
group to some other molecule, such as a
reactant
• The recipient molecule is now phosphorylated
• The three types of cellular work (mechanical,
transport, and chemical) are powered by the
hydrolysis of ATP

33. LE 8-11
NH2
Glu
P i
P i
P i
P i
Glu
NH3
P
P
P
ATP
ADP
Motor protein
Mechanical work: ATP phosphorylates motor proteins
Protein moved
Membrane
protein
Solute
Transport work: ATP phosphorylates transport proteins
Solute transported
Chemical work: ATP phosphorylates key reactants
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made
+ +
+

34. P
i
ADP
Energy for cellular work
(endergonic, energy-
consuming processes)
Energy from catabolism
(energonic, energy-
yielding processes)
ATP
+
The Regeneration of ATP
•ATP is a renewable resource that is regenerated by addition of a
phosphate group to 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

35. Enzymes speed up metabolic
reactions by providing an alternative
pathway with a lower EA
• A catalyst is a chemical agent that speeds up a
reaction without being consumed by the
reaction
• An enzyme is a catalytic protein or RNA
• Hydrolysis of sucrose by the enzyme sucrase
is an example of an enzyme-catalyzed reaction

36. LE 8-13
Sucrose
C12H22O11
Glucose
C6H12O6
Fructose
C6H12O6

37. The Activation Energy Barrier
• Every chemical reaction between molecules
involves bond breaking and bond forming
• The initial energy needed to start a chemical
reaction is called the free energy of activation,
or activation energy (EA)
• Activation energy is often supplied in the form
of heat from the surroundings

38. LE 8-14
Transition state
C D
A B
EA
Products
C D
A B
∆G < O
Progress of the reaction
Reactants
C D
A B
Freeenergy

39. How Enzymes Lower the EA
Barrier
• Enzymes catalyze reactions by lowering the
EA barrier—provide an alternative transition
state
• Enzymes do not affect the change in free-
energy (∆G); instead, they hasten reactions
that could occur eventually

40. 3. In the energy diagram below, which of the
energy changes would be the same in both the
enzyme-catalyzed and uncatalyzed reactions?
a
b
c
d
e

41. 3. In the energy diagram below, which of the
energy changes would be the same in both the
enzyme-catalyzed and uncatalyzed reactions?
a
b
c
d
e

42. LE 8-15
Course of
reaction
without
enzyme
EA
without
enzyme
∆G is unaffected
by enzyme
Progress of the reaction
Freeenergy
EA with
enzyme
is lower
Course of
reaction
with enzyme
Reactants
Products

43. Substrate Specificity of
Enzymes
• The reactant that an enzyme acts on is called
the enzyme’s substrate
• The enzyme binds to its substrate, forming an
enzyme-substrate complex
• The active site is the region on the enzyme
where the substrate binds
• Induced fit of a substrate brings chemical
groups of the active site into positions that
enhance their ability to catalyze the reaction

44. LE 8-16
Substrate
Active site
Enzyme Enzyme-substrate
complex
If reversible, what are the possible types of bonds utilized
by enzymes in their active sites?

45. Catalysis in the Enzyme’s
Active Site
• In an enzymatic reaction, the substrate binds to
the active site
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate

46. LE 8-17
Enzyme-substrate
complex
Substrates
Enzyme
Products
Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
Active site (and R groups of
its amino acids) can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
Substrates are
converted into
products.
Products are
released.
Active
site is
available
for two new
substrate
molecules.

47. Effects of Local Conditions on
Enzyme Activity
• An enzyme’s activity can be affected by:
– General environmental factors, such as
temperature and pH
– Chemicals that specifically influence the
enzyme
• Each enzyme has an optimal temperature in
which it can function
• Each enzyme has an optimal pH in which it
can function
We can find these in lab the next few weeks!

48. LE 8-18
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant
bacteria)
Temperature (°C)
Optimal temperature for two enzymes
0 20 40 60 80 100
Rateofreaction
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme)
pH
Optimal pH for two enzymes
0
Rateofreaction
1 2 3 4 5 6 7 8 9 10
Explain what is
happening at each
section of the curve.

50. Cofactors
• Cofactors are nonprotein enzyme helpers
• Coenzymes are organic cofactors
Enzyme Inhibitors
• 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

51. LE 8-19
Substrate
Active site
Enzyme
Competitive
inhibitor
Normal binding
Competitive inhibition
Noncompetitive inhibitor
Noncompetitive inhibition
A substrate can
bind normally to the
active site of an
enzyme.
A competitive
inhibitor mimics the
substrate, competing
for the active site.
A noncompetitive
inhibitor binds to the
enzyme away from the
active site, altering the
conformation of the
enzyme so that its
active site no longer
functions.

52. Concept 8.5: Regulation of
enzyme activity helps control
metabolism
• Chemical chaos would result if a cell’s
metabolic pathways were not tightly regulated
• To regulate metabolic pathways, the cell
switches on or off the genes that encode
specific enzymes

53. Allosteric Regulation of
Enzymes
• Allosteric regulation is the term used to
describe cases where a protein’s function at
one site is affected by binding of a regulatory
molecule at another site
• Allosteric regulation may either inhibit or
stimulate an enzyme’s activity

54. Allosteric Activation and
Inhibition
• 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

55. LE 8-20a
Allosteric enzyme
with four subunits
Regulatory
site (one
of four) Active form
Activator
Stabilized active form
Active site
(one of four)
Allosteric activator
stabilizes active form.
Non-
functional
active site
Inactive form
Inhibitor
Stabilized inactive
form
Allosteric inhibitor
stabilizes inactive form.
Oscillation
Allosteric activators and inhibitors

56. • 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

57. LE 8-20b
Substrate
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Cooperativity another type of allosteric activation
Stabilized active formInactive form

58. Michaelis-Menton

59. Lineweaver-Burk analysis is one method of linearizing substrate-velocity data so
as to determine the kinetic constants Km and Vmax. One creates a secondary,
reciprocal plot: 1/velocity vs. 1/[substrate]. When catalytic activity follows
Michaelis-Menten kinetics over the range of substrate concentrations tested, the
Lineweaver-Burk plot is a straight line with
Y intercept = 1/Vmax,
X intercept = -1/Km
slope = Km/Vmax

60. 4. Which choice best describes what the H+
−ATPase does in terms of flow of energy in
many cells?
a. It converts light energy into energy
in a concentration gradient.
b. It converts matter into energy in the
form of an electrochemical
gradient.
c. It pumps protons up their pressure
gradient.
d. It converts chemical energy to
energy in an electrochemical
gradient and heat.
e. It converts energy in a
concentration gradient
to energy in an electrical gradient.

61. 4. Which choice best describes what the H+
−ATPase does in terms of flow of energy in
many cells?
a. It converts light energy into energy
in a concentration gradient.
b. It converts matter into energy in the
form of an electrochemical
gradient.
c. It pumps protons up their pressure
gradient.
d. It converts chemical energy to
energy in an electrochemical
gradient and heat.
e. It converts energy in a
concentration gradient
to energy in an electrical gradient.

62. 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

63. LE 8-21
Active site
available
Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Enzyme 2
Intermediate A
Isoleucine
used up by
cell
Feedback
inhibition Active site of
enzyme 1 can’t
bind
theonine
pathway off
Isoleucine
binds to
allosteric
site
Enzyme 3
Intermediate B
Enzyme 4
Intermediate C
Enzyme 5
Intermediate D
End product
(isoleucine)

64. 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 (oxidative phosphorylation in
Ch.9; photsynthetic phosphorylation in Ch.10)
• Some enzymes reside in specific organelles,
such as enzymes for cellular respiration being
located in mitochondria— next chapter

65. LE 8-22
Mitochondria,
sites of cellular respiration
1 µm