1. An Introduction to Metabolism
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

4. 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

5. 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

6. LE 8-UN141
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting
molecule
Product

7. Catabolic pathways release energy by breaking down complex molecules into simpler compounds
Anabolic pathways consume energy to build complex molecules from simpler ones
Bioenergetics is the study of how organisms manage their energy resources

8. Forms of Energy Energy is the capacity to cause change
Energy exists in various forms, some of which can perform work

9. Animation: Energy Concepts
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
Animation: Energy Concepts

10. LE 8-2 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.

11. 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

12. 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

13. 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

14. LE 8-3 CO2 Chemical energy Heat H2O First law of thermodynamics
Second law of thermodynamics

15. Living cells unavoidably convert organized forms of energy to heat
Spontaneous processes occur without energy input; they can happen quickly or slowly
For a process to occur without energy input, it must increase the entropy of the universe

16. 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

17. Concept 8.2: The free-energy change of a reaction tells us whether the reaction occurs spontaneously
Biologists want to know which reactions occur spontaneously and which require input of energy
To do so, they need to determine energy changes that occur in chemical reactions

18. Free-Energy Change, G
A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell

19. 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
Only processes with a negative ∆G are spontaneous
Spontaneous processes can be harnessed to perform work

20. Free Energy, Stability, and Equilibrium
Free energy is a measure of a system’s instability, its tendency to change to a more stable state
During a spontaneous change, free energy decreases and the stability of a system increases
Equilibrium is a state of maximum stability
A process is spontaneous and can perform work only when it is moving toward equilibrium

21. LE 8-5
Gravitational motion
Diffusion
Chemical reaction

22. Free Energy and Metabolism
The concept of free energy can be applied to the chemistry of life’s processes

23. Exergonic and Endergonic Reactions in Metabolism
An exergonic reaction proceeds with a net release of free energy and is spontaneous
An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous

24. Progress of the reaction
LE 8-6a
Reactants
Amount of
energy
released
(G < 0)
Free energy
Energy
Products
Progress of the reaction
Exergonic reaction: energy released

25. Progress of the reaction
LE 8-6b
Products
Amount of
energy
required
(G > 0)
Free energy
Energy
Reactants
Progress of the reaction
Endergonic reaction: energy required

26. 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

27. LE 8-7a
G < 0
G = 0
A closed hydroelectric system

28. LE 8-7b
G < 0
An open hydroelectric system

29. G < 0 G < 0 G < 0 A multistep open hydroelectric system

30. 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

31. The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP provides energy for cellular functions

32. LE 8-8
Adenine
Phosphate groups
Ribose

33. 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

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

35. 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

36. Glutamic acid Ammonia Glutamine ATP H2O ADP
LE 8-10
Endergonic reaction: DG is positive, reaction
is not spontaneous
NH2 +
NH3
DG = +3.4 kcal/mol
Glu
Glu
Glutamic
acid
Ammonia
Glutamine
Exergonic reaction: DG is negative, reaction
is spontaneous
ATP +
H2O
ADP P +
DG = –7.3 kcal/mol i
Coupled reactions: Overall DG is negative;
together, reactions are spontaneous
DG = –3.9 kcal/mol

37. 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

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

39. 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

40. Energy for cellular work (endergonic, energy- consuming processes)
LE 8-12
ATP
Energy for cellular work
(endergonic, energy-
consuming processes)
Energy from catabolism
(energonic, energy-
yielding processes)
ADP P + i

41. 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

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

43. 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

44. Progress of the reaction
LE 8-14 A B C D
Transition state A B EA
Free energy C D
Reactants A B
DG < O C D
Products
Progress of the reaction

45. How Enzymes Lower the EA Barrier
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
Animation: How Enzymes Work

46. Progress of the reaction
LE 8-15
Course of
reaction
without
enzyme EA
without
enzyme
EA with
enzyme
is lower
Reactants
Free energy
Course of
reaction
with enzyme
DG is unaffected
by enzyme
Products
Progress of the reaction

47. 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

48. LE 8-16
Substrate
Active site
Enzyme
Enzyme-substrate
complex

49. 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

50. LE 8-17 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
Enzyme-substrate
complex
Active
site is
available
for two new
substrate
molecules.
Enzyme
Products are
released.
Substrates are
converted into
products.
Products

51. 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

52. Effects of Temperature and pH
Each enzyme has an optimal temperature in which it can function
Each enzyme has an optimal pH in which it can function

53. LE 8-18 Optimal temperature for typical human enzyme
enzyme of thermophilic
(heat-tolerant
bacteria)
Rate of reaction 20 40 60 80
100
Temperature (°C)
Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme)
Rate of reaction 1 2 3 4 5 6 7 8 9 10 pH
Optimal pH for two enzymes

54. Cofactors Cofactors are nonprotein enzyme helpers
Coenzymes are organic cofactors

55. 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

56. LE 8-19 A substrate can Substrate bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Competitive
inhibitor
Competitive inhibition
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.
Noncompetitive inhibitor
Noncompetitive inhibition

57. 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

58. 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

59. 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

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

61. 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

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

63. 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

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

65. 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
Some enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria

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