1. 8 An Introduction to Metabolism Chapter 8 Metabolism8
An Introduction to Metabolism
Lecture Presentation by Nicole Tunbridge and
Kathleen Fitzpatrick
Unit 1: Chem of Life

2. Chapter 8 Metabolism
The Energy of Life
The living cell is a miniature chemical factory where thousands of reactions occur
Extracts energy stored in sugars and other molecules
Energy is used to perform work and is the capacity to cause change.
Energy can be converted from one form to another
Example: Convert energy to light, or bioluminescence
Unit 1: Chem of Life

3. Forms of Energy Kinetic: Motion
Heat (thermal): Kinetic energy due to the movement of atoms or molecules
Potential: Energy that matter possesses due to its location, or structure
Chemical: Potential energy available for release in a chemical reaction

4. Figure 8.2 A diver has more potential Diving converts
Chapter 8 Metabolism
A diver has more potential
energy on the platform
than in the water.
Diving converts
potential energy to
kinetic energy.
Figure 8.2
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.
Unit 1: Chem of Life

5. Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
Metabolism
All of an organism’s chemical reactions
Emergent property of life
Arises from orderly interactions between molecules

6. Organization of the Chemistry of Life into Metabolic Pathways
Begins with a specific molecule
Ends with a specific product
Each step is catalyzed by a specific enzyme
Enzyme 1
Enzyme 2
Enzyme 3
Reaction 1
Reaction 2
Reaction 3
Product
Starting
molecule A B C D

7. Catabolic Pathways Anabolic Pathways Bioenergetics
Energy released by breaking down complex molecules into simpler compounds
Example: Cellular Respiration
Anabolic Pathways
Energy consumed to build complex molecules from simpler ones
Example: Protein Synthesis
Bioenergetics
The study of how energy flows through living organisms

8. The Laws of Energy Transformation
Thermodynamics
Study of energy transformations
Isolated System:
Unable to exchange energy or matter with its surroundings
Open System:
Energy and matter can be transferred between the system and its surroundings
Organisms are open systems

9. The First Law of Thermodynamics
Conservation of Energy
The energy of the universe is constant
Energy can be transferred and transformed, but it cannot be created or destroyed

10. The Second Law of Thermodynamics
Every energy transfer or transformation increases the entropy (disorder) of the universe
During every energy transfer or transformation, some energy is unusable, and/or is lost as heat
Living cells unavoidably convert organized forms of energy to heat
Spontaneous Processes
Occur without energy input; happen quickly or slowly
A process occurring without energy input increases the entropy of the universe.

11. 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
Energy flows into an ecosystem in the form of light and exits in the form of heat

12. Concept 8.2: The free-energy change of a reaction tells us whether or not 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

13. Free-Energy Change, G
A living system’s free energy is energy that can do work when temperature and pressure are uniform
The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin units (T)
∆G = ∆H - T∆S
Only processes with a negative ∆G are spontaneous
Spontaneous processes can be harnessed to perform work

14. 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

15. • More free energy (higher G) • Less stable • Greater work capacity
Figure 8.5
Chapter 8 Metabolism
• 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
Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change
• Less free energy (lower G)
• More stable
• Less work capacity
(a) Gravitational motion
(b) Diffusion
(c) Chemical reaction
Unit 1: Chem of Life

16. Free Energy and Metabolism
Exergonic reaction: energy released,
spontaneous
Endergonic reaction: energy required,
nonspontaneous
(a)
(b)
Free energy
Reactants
Energy
Products
Amount of
energy
released
(∆G < 0)
required
(∆G > 0)
Progress of the reaction
The concept of free energy can be applied to the chemistry of life’s processes
Exergonic Reaction:
Net release of free energy
Spontaneous
Endergonic Reaction:
Absorbs free energy from surroundings
Nonspontaneous

17. 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 defining feature of life is that metabolism is never at equilibrium
A catabolic pathway in a cell releases free energy in a series of reactions

18. ∆G < 0 ∆G = 0 Chapter 8 Metabolism Figure 8.7
Figure 8.7 Equilibrium and work in an isolated hydroelectric system
Unit 1: Chem of Life

19. ∆G < 0 ∆G < 0 ∆G < 0 ∆G < 0
Chapter 8 Metabolism
Figure 8.8
(a)
An open hydro-
electric system
∆G < 0
∆G < 0
∆G < 0
∆G < 0
Figure 8.8 Equilibrium and work in open systems
(b) A multistep open hydroelectric system
Unit 1: Chem of Life

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

21. The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle
Ribose (a sugar)
Adenine (a nitrogenous base)
3 phosphate groups
Energy is released from ATP when the terminal phosphate bond is broken
Hydrolysis breaks bonds between the 2 phosphate groups at the end of ATP’s tail
Release of energy due to chemical change to a state of lower free energy,
Energy not from the phosphate bonds themselves

22. Adenosine diphosphate
Figure 8.9
Chapter 8 Metabolism
Adenine
Triphosphate group
(3 phosphate groups)
Ribose
(a) The structure of ATP
Adenosine triphosphate (ATP)
H2O
Figure 8.9 The structure and hydrolysis of adenosine triphosphate (ATP)
Energy
Inorganic
phosphate
Adenosine diphosphate
(ADP)
(b) The hydrolysis of ATP
Unit 1: Chem of Life

23. How the Hydrolysis of ATP Performs Work
Hydrolysis of ATP powers cellular work
Mechanical, transport, and chemical
Can lead to a change in protein shape and binding ability
Energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction
ATP drives endergonic reactions by phosphorylation
Transfer of a phosphate group to another molecule
Phosphorylated Intermediate
Overall, the coupled reactions are exergonic

24. i i ∆GGlu = +3.4 kcal/mol Glutamic acid Ammonia Glutamine
Figure 8.10
Chapter 8 Metabolism
NH3
NH2
∆GGlu
= +3.4 kcal/mol
Glu
Glu
Glutamic acid
Ammonia
Glutamine
(a) Glutamic acid conversion to glutamine
NH3 P 1 2
NH2
ADP
ADP P i
Glu
ATP
Glu
Glu
Glutamic acid
Phosphorylated
intermediate
Glutamine
(b) Conversion reaction coupled with ATP hydrolysis
∆GGlu
= +3.4 kcal/mol
Figure 8.10 How ATP drives chemical work: energy coupling using ATP hydrolysis
NH3
NH2
ATP
ADP P i
Glu
Glu
∆GGlu
= +3.4 kcal/mol
∆GATP
= −7.3 kcal/mol
+ ∆GATP
= −7.3 kcal/mol
Net ∆G
= −3.9 kcal/mol
(c) Free-energy change for coupled reaction
Unit 1: Chem of Life

25. (a) Transport work: ATP phosphorylates transport proteins.
Chapter 8 Metabolism
Figure 8.11
Transport protein
Solute
ATP
ADP P i P P i
Solute transported
(a) Transport work: ATP phosphorylates transport proteins.
Vesicle
Cytoskeletal track
Figure 8.11 How ATP drives transport and mechanical work
ATP
ADP P
ATP i
Motor protein
Protein and vesicle moved
(b)
Mechanical work: ATP binds noncovalently to motor
proteins and then is hydrolyzed.
Unit 1: Chem of Life

26. The Regeneration of ATP
Chapter 8 Metabolism
The Regeneration of ATP
ATP can be recycled
Regenerated by adding a phosphate group to adenosine diphosphate (ADP)
The energy to phosphorylate ADP comes from catabolic reactions in the cell
Energy from
catabolism
(exergonic, energy-
releasing processes)
Energy for cellular
work (endergonic
energy-consuming
processes)
ADP P i
H2O
ATP
Unit 1: Chem of Life

27. Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers
Catalyst
Chemical agent that speeds up a reaction, but is not consumed by the reaction
An enzyme is a catalytic protein.
Example: Sucrase
Hydrolysis of sucrose by sucrase
Sucrose
(C12H22O11)
Glucose
(C6H12O6)
Fructose
Sucrase

28. The Activation Energy Barrier
Activation Energy (EA)
The initial energy needed to start a chemical reaction
Often supplied in the form of thermal energy
Absorbed by reactant molecules from surroundings
Every chemical reaction between molecules involves the breaking and forming of bonds.

29. Progress of the reaction
Figure 8.13
Chapter 8 Metabolism A B C D
Transition state A B EA
Free energy C D
Reactants A B
Figure 8.13 Energy profile of an exergonic reaction
∆G < O C D
Products
Progress of the reaction
Unit 1: Chem of Life

30. How Enzymes Speed Up Reactions
Enzymes catalyze reactions by lowering the EA barrier
Enzymes do not affect the change in free energy (∆G).
They hasten reactions that would occur eventually

31. Progress of the reaction
Figure 8.14
Chapter 8 Metabolism
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 8.14 The effect of an enzyme on activation energy
Products
Progress of the reaction
Unit 1: Chem of Life

32. Substrate Specificity of Enzymes
Reactant acted on by an enzyme
The enzyme binds to its substrate, forming an enzyme- substrate complex
Active Site: Region of enzyme where substrate binds
The reaction catalyzed by each enzyme is very specific
Induced Fit
A substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction

33. Substrate Active site Enzyme Enzyme-substrate complex Figure 8.15
Chapter 8 Metabolism
Substrate
Active site
Figure 8.15 Induced fit between an enzyme and its substrate
Enzyme
Enzyme-substrate
complex
Unit 1: Chem of Life

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

35. Substrates enter active site. Substrates are held in active
Chapter 8 Metabolism
Figure 1
Substrates enter
active site. 2
Substrates are
held in active
site by weak
interactions.
Substrates
Enzyme-substrate
complex 5
Active site
is available
for new
substrates.
Enzyme
Figure The active site and catalytic cycle of an enzyme (step 4) 4
Products are
released. 3
Substrates are
converted to
products.
Products
Unit 1: Chem of Life

36. Effects of Local Conditions on Enzyme Activity
An enzyme’s activity can be affected by environmental factors
Chemicals that specifically influence the enzyme
Temperature and pH
Each enzyme has an optimal temperature and pH in which it can function
Optimal conditions favor the most active shape for the enzyme molecule

37. Optimal temperature for typical human enzyme (37C)
Chapter 8 Metabolism
Figure 8.17
Optimal temperature for
typical human enzyme
(37C)
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria (77C)
Rate of reaction 20 40 60 80
100
120
Temperature (C)
(a) Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach
enzyme)
Optimal pH for trypsin
(intestinal
enzyme)
Figure 8.17 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
Unit 1: Chem of Life

38. Cofactors Cofactors Coenzyme Nonprotein enzyme helpers
Cofactors may be organic or inorganic (ionic metals)
Coenzyme
An organic cofactor
Example: Vitamins

39. Enzyme Inhibitors Competitive Inhibitors Noncompetitive Inhibitors
Bind to the active site of an enzyme
Compete with the substrate
Noncompetitive Inhibitors
Bind to another part of an enzyme
Cause enzyme to change shape
Makes the active site less effective
Examples: toxins, poisons, pesticides, and antibiotics

40. (b) Competitive inhibition (c) Noncompetitive inhibition
Figure 8.18
Chapter 8 Metabolism
(a) Normal binding
(b) Competitive inhibition
(c)
Noncompetitive
inhibition
Substrate
Active site
Competitive
inhibitor
Enzyme
Figure 8.18 Inhibition of enzyme activity
Noncompetitive
inhibitor
Unit 1: Chem of Life

41. The Evolution of Enzymes
Enzymes are proteins encoded by genes
Changes (mutations) in genes lead to changes in amino acid composition of an enzyme
Altered amino acids in enzymes may result in novel enzyme activity or altered substrate specificity
Under new environmental conditions a novel form of an enzyme might be favored
Example: 6 amino acid changes improved substrate binding and breakdown in E. coli

42. Two changed amino acids were found near the active site. Active site
Figure 8.19
Chapter 8 Metabolism
Two changed amino acids were
found near the active site.
Active site
Figure 8.19 Mimicking evolution of an enzyme with a new function
Two changed amino acids
were found in the active site.
Two changed amino acids
were found on the surface.
Unit 1: Chem of Life

43. Concept 8.5: Regulation of enzyme activity helps control metabolism
Metabolic pathways are regulated by cells
Cells switch genes for specific enzymes on or off
Regulate the activity of enzymes
Allosteric Regulation
A regulatory molecule binds to a protein at one site and affects the protein’s function at another site
Can inhibit or stimulate an enzyme’s activity

44. 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

45. (a) Allosteric activators and inhibitors
Chapter 8 Metabolism
Figure 8.20
(a) Allosteric activators and inhibitors
(b) Cooperativity: another type of allosteric activation
Allosteric enzyme
with four subunits
Active site
(one of four)
Substrate
Regulatory
site (one
of four)
Activator
Active form
Stabilized
active form
Inactive form
Stabilized
active form
Oscillation
Non-
functional
active site
Figure 8.20 Allosteric regulation of enzyme activity
Inhibitor
Inactive form
Stabilized
inactive form
Unit 1: Chem of Life

46. Cooperativity Feedback Inhibition
A form of allosteric regulation that amplifies enzyme activity
One substrate molecule primes an enzyme to act on additional substrate molecules more readily
Feedback Inhibition
The end product of a metabolic pathway shuts down the pathway
Prevents a cell from wasting chemical resources by synthesizing more product than is needed

47. Active site available Threonine in active site Enzyme 1 (threonine
Figure 8.21
Chapter 8 Metabolism
Active site available
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Active
site no
longer
available;
pathway
is halted.
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site.
Enzyme 4
Figure 8.21 Feedback inhibition in isoleucine synthesis
Intermediate D
Enzyme 5
End product
(isoleucine)
Unit 1: Chem of Life

48. 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

49. enzymes in solution that are involved on one stage
Figure 8.22
Chapter 8 Metabolism
Mitochondria
The matrix contains
enzymes in solution that
are involved on one stage
of cellular respiration.
Figure 8.22 Organelles and structural order in metabolism
Enzymes for another
stage of cellular
respiration are
embedded in the
inner membrane
1 µm
Unit 1: Chem of Life