1. Chapter 8: An Introduction to Metabolism
Mrs. Valdes
AP Biology

2. Overview: The Energy of Life
Living cell = miniature chemical factory where thousands of reactions occur
Cell extracts energy  applies it to perform work
Some organisms convert energy  light, bioluminescence

3. Organization of the Chemistry of Life into Metabolic Pathways
Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
Metabolism: totality of organism’s chemical reactions
an emergent property of life that arises from interactions between molecules within the cell
Organization of the Chemistry of Life into Metabolic Pathways
Metabolic pathway: begins with specific molecule and ends with a product
Each step catalyzed by a specific enzyme

4. Organization of the Chemistry of Life into Metabolic Pathways
Catabolic pathways: release energy by breaking down complex molecules into simpler compounds
Ex: Cellular respiration= the breakdown of glucose in the presence of oxygen
Anabolic pathways: consume energy to build complex molecules from simpler ones
Ex: synthesis of protein from amino acids
Bioenergetics: study of how organisms manage their energy resources

5. Forms of Energy Kinetic energy: energy associated with motion
Energy: the capacity to cause change
exists in various forms, some can perform work
Kinetic energy: energy associated with motion
Heat (thermal energy): kinetic energy associated with random movement of atoms or molecules
Potential energy: energy that matter possesses because of its location or structure
Chemical energy: potential energy available for release in a chemical reaction
Energy can be converted from one form to another

6. 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.

7. The Laws of Energy Transformation
Thermodynamics: study of energy transformations
Closed system is isolated from its surroundings
Ex: liquid in a thermos,
In open system energy and matter can be transferred between the system and its surroundings
Ex: Organisms!
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8. The First Law of Thermodynamics
First law of thermodynamics: energy of the universe is constant:
– Energy can be transferred and transformed, but it cannot be created or destroyed
Also called the principle of conservation of energy

9. The Second Law of Thermodynamics
Second law of thermodynamics: during every energy transfer or transformation, some energy is unusable, and is often lost as heat
Every energy transfer or transformation increases the entropy (disorder) of the universe
Living cells unavoidably convert organized energy forms  heat
Spontaneous processes occur without energy input quickly or slowly
For a process to occur without energy input, it must increase the entropy of universe

10. (a) First law of thermodynamics (b) Second law of thermodynamics
Fig. 8-3
Heat
CO2 +
Chemical
energy
H2O
Figure 8.3 The two laws of thermodynamics
(a) First law of thermodynamics
(b) Second law of thermodynamics

11. Biological Order and Disorder
Cells create ordered structures from less ordered materials
Organisms replace ordered forms of matter and energy with less ordered forms
Energy:
Flows into an ecosystem as light and
Exits as heat
Explain this.
Evolution of more complex organisms does not violate the second law of thermodynamics
Why not?
Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

12. Root of buttercup plant;
Fig. 8-4
Root of buttercup plant;
As open system, plants can increase their order as long as order of surroundings decrease
Figure 8.4 Order as a characteristic of life
50 µm

13. 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
THUS! they need to determine energy changes that occur in chemical reactions

14. Free-Energy Change, G
Free energy: energy that can do work when temperature and pressure are uniform like in a living cell
Change in free energy (∆G) during a process is related to change in enthalpy/change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T):
∆G = ∆H – T∆S
Only processes with a negative ∆G are spontaneous
Spontaneous processes can be harnessed to perform work
Can you think of one?
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

16. 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
(b) Diffusion
(c) Chemical reaction

17. More free energy (higher G) Less stable Greater work capacity
Fig. 8-5a
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

18. (a) Gravitational motion (b) Diffusion (c) Chemical reaction
Fig. 8-5b
Spontaneous
change
Spontaneous
change
Spontaneous
change
Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change
(a) Gravitational motion
(b) Diffusion
(c) Chemical reaction

19. Free Energy and Metabolism
Concept of free energy can be applied to chemistry of life’s processes
Exergonic reaction: net release of free energy; spontaneous
Endergonic reaction: absorbs free energy from its surroundings; nonspontaneous

20. 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
(a) Exergonic reaction: energy released

21. 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: energy required

22. Equilibrium and Metabolism
Reactions in closed system eventually reach equilibrium and then do no work
Cells not in equilibrium; they are open systems with constant flow of materials
Defining feature of life = metabolism is never at equilibrium
Catabolic pathway: releases free energy in a series of reactions
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

23. Figure 8.7 Equilibrium and work in isolated and open systems
(a) An isolated hydroelectric system
(b) An open hydroelectric
system
∆G < 0
Figure 8.7 Equilibrium and work in isolated and open systems
∆G < 0
∆G < 0
∆G < 0
(c) A multistep open hydroelectric system

24. (a) An isolated hydroelectric system
Fig. 8-7a
∆G < 0
∆G = 0
Figure 8.7a Equilibrium and work in isolated and open systems
(a) An isolated hydroelectric system

25. (b) An open hydroelectric system
Fig. 8-7b
∆G < 0
Figure 8.7b Equilibrium and work in isolated and open systems
(b) An open hydroelectric system

26. (c) A multistep open hydroelectric system
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

27. Cell does three main kinds of work:
Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions
Cell does three main kinds of work:
Chemical
Transport
Mechanical
Cells manage energy resources by energy coupling
the use of an exergonic process to drive an endergonic one
Most energy coupling in cells mediated by ATP
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

28. The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate): cell’s energy shuttle
ATP is composed of :
ribose (a sugar)
adenine (a nitrogenous base)
three phosphate groups
Bonds between phosphate groups of ATP’s tail can be broken by hydrolysis
Energy released from ATP when terminal phosphate bond broken
comes from chemical change to a state of lower free energy, not from the phosphate bonds themselves
For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.

29. How ATP Performs Work
Three types of cellular work (mechanical, transport, and chemical) powered by the hydrolysis of ATP
In cell energy from exergonic reaction of ATP hydrolysis can be used to drive a endergonic reaction
Overall: coupled reactions are exergonic
ATP drives endergonic reactions by phosphorylation
transferring a phosphate group to some other molecule, such as a reactant
recipient molecule is now phosphorylated

30. ∆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

31. The Regeneration of ATP
ATP renewable resource that is regenerated by addition of phosphate group to adenosine diphosphate (ADP)
Energy to phosphorylate ADP comes from catabolic reactions in the cell
Chemical potential energy temporarily stored in ATP drives most cellular work
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

32. Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers
Catalyst: chemical agent that speeds up a reaction without being consumed by the reaction
Enzyme: catalytic protein
Enzyme-catalyzed reaction
Ex: Hydrolysis of sucrose by enzyme sucrase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

33. The Activation Energy Barrier
Every chemical reaction between molecules involves bond breaking AND bond forming
Free energy of activation, or activation energy (EA): initial energy needed to start chemical reaction
often supplied in form of heat from the surroundings

34. How Enzymes Lower the EA Barrier
Enzymes catalyze reactions by lowering EA barrier
Enzymes do not affect change in free energy (∆G); instead, they hasten reactions that would occur eventually

35. Substrate Specificity of Enzymes
Substrate: reactant that an enzyme acts on
Enzyme-substrate complex: formed when enzyme binds to its substrate
Active site: region on the enzyme where the substrate binds
Induced fit of substrate brings chemical groups of active site into positions that enhance their ability to catalyze the reaction
For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.

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

37. 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
Figure 8.17 The active site and catalytic cycle of an enzyme
Enzyme 5
Products are
released.
Substrates are
converted to
products. 4
Products

38. Effects of Local Conditions on Enzyme Activity
Enzyme’s activity can be affected by
General environmental factors
Temperature pH
Chemicals that specifically influence enzyme

39. 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
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

40. Cofactors Cofactors: nonprotein enzyme helpers
may be inorganic (such as a metal in ionic form) or organic
Coenzyme: organic cofactor
include vitamins
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

41. Enzyme Inhibitors
Competitive inhibitors: bind to active site of enzyme, competing with the substrate
Noncompetitive inhibitors: bind to another part of enzyme, causing enzyme to change shape and making active site less effective
Examples: toxins, poisons, pesticides, and antibiotics

42. Noncompetitive inhibitor
Fig. 8-19
Substrate
Active site
Competitive
inhibitor
Enzyme
Figure 8.19 Inhibition of enzyme activity
Noncompetitive inhibitor
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition

43. Concept 8.5: Regulation of enzyme activity helps control metabolism
Chemical chaos would result if cell’s metabolic pathways were not tightly regulated
Cell does this by:
switching on/off genes that encode specific enzymes
regulating the activity of enzymes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

44. Allosteric Regulation of Enzymes
Allosteric regulation may either inhibit or stimulate an enzyme’s activity
occurs when a regulatory molecule binds to protein at one site and affects the protein’s function at another site

45. Allosteric Activation and Inhibition
Most allosterically regulated enzymes made from polypeptide subunits
Each enzyme has active and inactive forms
Binding of activator stabilizes the active form of the enzyme
Binding of inhibitor stabilizes the inactive form of the enzyme
Cooperativity: form of allosteric regulation that can amplify enzyme activity
binding by substrate to one active site stabilizes favorable conformational changes at all other subunits

46. 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

47. (b) Cooperativity: another type of allosteric activation
Fig. 8-20b
Substrate
Inactive form
Stabilized active
form
Figure 8.20b Allosteric regulation of enzyme activity
(b) Cooperativity: another type of allosteric activation

48. Identification of Allosteric Regulators
Allosteric regulators = attractive drug candidates for enzyme regulation
Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses

49. EXPERIMENT Allosteric binding site Allosteric inhibitor Caspase 1
Fig. 8-21a
EXPERIMENT
Caspase 1
Active
site
Substrate SH SH
Known active form
Active form can
bind substrate
Figure 8.21 Are there allosteric inhibitors of caspase enzymes?
Allosteric
binding site SH
S–S
Allosteric
inhibitor
Known inactive form
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form

50. RESULTS Caspase 1 Inhibitor Active form Allosterically inhibited form
Fig. 8-21b
RESULTS
Caspase 1
Inhibitor
Figure 8.21 Are there allosteric inhibitors of caspase enzymes?
Active form
Allosterically
inhibited form
Inactive form

51. Feedback Inhibition
Feedback inhibition: end product of a metabolic pathway shuts down the pathway
Prevents cell from wasting chemical resources by synthesizing more product than needed

52. Specific Localization of Enzymes Within the Cell
Structures within cell help bring order to metabolic pathways
Some enzymes act as structural components of membranes
In eukaryotic cells, some enzymes reside in specific organelles
Ex: enzymes for cellular respiration located in mitochondria
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

53. 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

54. 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