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

2. Metabolism is the totality of an organism’s chem rxns
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 chem rxns
An emergent property of life that arises from interactions between molecules w/in the cell
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3. Organization of the Chemistry of Life into Metabolic Pathways
a sequence of steps,
each controlled by an ,
converts a specific molecule into a product.
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4. Catabolic pathways release E by breaking down complex molecules into simpler cmpds
CR, the breakdown of C6H12O6 in the presence of O2
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5. Bioenergetics is the study of how organisms manage their E resources
Anabolic pathways (biosynthesis pathways) require E to build complex molecules from simpler ones
The synthesis of protein from amino acids
Bioenergetics is the study of how organisms manage their E resources
The E released from catabolic pathways drives the anabolic pathways in a cell.
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6. Energy is the capacity to cause ∆
Forms of Energy
Energy is the capacity to cause ∆
E exists in various forms, some of which can perform work
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7. Animation: Energy Concepts
Kinetic energy is E associated with motion
Heat (thermal energy) is KE associated with random mvmnt of atoms or molecules
Potential energy is the capacity of matter to cause a Δ as a consequence of its location or arrangement
Chemical energy is PE available for release in a chem rxn
E can be converted from one form to another
Animation: Energy Concepts
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8. The Laws of Energy Transformation
Thermodynamics is the study of E transformations
A closed system, such as that approximated by liquid in a thermos, is isolated from its surroundings
In an open system, E and matter can be transferred between the system and its surroundings
Organisms are OPEN systems
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9. The First Law of Thermodynamics
According to the first law of thermodynamics, the E of the universe is constant:
– E can be transferred and transformed, but it cannot be created or destroyed
The first law is also called the law of conservation of E
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10. The Second Law of Thermodynamics
During E transfer or transformation, some E is unusable, and is often “lost” as heat
According to the second law of thermodynamics:
– Every E transfer or transformation increases the entropy (disorder) of the universe
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11. (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

12. Living cells unavoidably convert organized forms of E to heat
Spontaneous processes occur without E input; they can happen quickly or slowly
For a process to occur without E input, it must ↑ the entropy of the universe
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13. Biological Order and Disorder
Cells create ordered structures from less ordered matls
Organisms also replace ordered forms of matter and E with less ordered forms
E flows into an ecosystem in the form of light and exits in the form of heat
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14. The evolution of more complex organisms does not violate the 2nd law of thermodynamics
Entropy (disorder) may  in an organism, but the universe’s total entropy ↑s
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15. k. ____ law of thermodynamics Arrangement of atoms in molecules light
ENERGY
Defined as is
Transfer leads to
may be a. b. d. f.
Increasing Disorder
Energy of
Energy of
neither
may be
Results in
called is is c. e. g. i. j.
Such as
Such as
k. ____ law of thermodynamics
Arrangement of atoms in molecules
Some energy converted to
light
heat
h. ____ law of thermodynamics
as in
heat

16. To do so, they need to determine E ∆s that occur in chem rxns
Concept 8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously
Biologists want to know which rxns occur spontaneously and which require input of E
To do so, they need to determine E ∆s that occur in chem rxns
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17. Free-Energy Change, G
A living system’s free energy is E that can do work when temp and pressure are uniform, as in a living cell
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18. Only processes with a negative ∆G are spontaneous
The change in free E (∆G) during a process is related to the ∆ in enthalpy, or ∆ in total energy (∆H), ∆ in entropy (∆S), and temperature in Kelvin (T):
∆G = ∆H – T∆S
Only processes with a negative ∆G are spontaneous
The system must lose E (H must decrease), become more disordered (TS must increase), or both
Spontaneous processes can be harnessed to perform work
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19. Free Energy, Stability, and Equilibrium
Free energy is a measure of a system’s instability
its tendency to ∆ to a more stable state
During a spontaneous ∆, free E s and the stability of a system ↑s
Equilibrium is a state of maximum stability
A process is spontaneous and can perform work only when it is moving toward equilibrium
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20. Free Energy and Metabolism
The concept of free E can be applied to the chemistry of life’s processes
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21. CHANGES IN FREE ENERGY IN A CELL
RESPIRATION BIOSYNTHESIS
Glucose  CO2 + H2O
Monomers  Macromolecules
Enzymes catalyze each
step in catabolic and
anabolic pathways
Catabolic Reaction
Decrease in
FREE ENERGY
(-) ΔG
Increase in
FREE ENERGY
(+) ΔG
Anabolic Reaction
EXERGONIC ENDERGONIC
Energy Shuttle
ATP

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

24. 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

25. Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions
A cell does 3 main kinds of work:
Chemical
Transport All powered by hydrolysis of ATP
Mechanical
To do work, cells manage E resources by E coupling, the use of an exergonic process to drive an endergonic one
Most E-coupling in cells is mediated by ATP
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26. The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s E shuttle
Adenine
For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.
Phosphate groups
Ribose
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27. E is released from ATP when the terminal phosphate bond is broken
The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis
E is released from ATP when the terminal phosphate bond is broken
This release of E comes from the chem ∆ to a state of lower free E, not from the phosphate bonds themselves
For the Cell Biology Video Stick Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

28. 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)

29. Overall, the coupled rxns are exergonic
How ATP Performs Work
The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP
In the cell, the E from the exergonic rxns of ATP hydrolysis can be used to drive an endergonic rxns
Overall, the coupled rxns are exergonic
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30. The recipient molecule is now phosphorylated
ATP drives endergonic rxns by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant
The recipient molecule is now phosphorylated
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31. Membrane protein Solute Solute transported Vesicle Cytoskeletal track
Fig. 8-11
Membrane protein 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

32. The Regeneration of ATP
ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
The E to phosphorylate ADP comes from catabolic rxns in the cell
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33. An enzyme is a catalytic protein
Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers
A catalyst is a chem agent that speeds up a rxn without being consumed by the rxn
An enzyme is a catalytic protein
Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed rxn
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34. 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)

35. The Activation Energy Barrier
The initial E needed to start a chem rxn is called the free energy of activation, or activation energy (EA)
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36. 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

37. How Enzymes Lower the EA Barrier
Enzymes catalyze rxns by lowering the EA barrier
Enzymes do not affect (∆G); instead, they hasten rxns that would occur eventually
Animation: How Enzymes Work
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38. 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

39. 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 chem groups of the active site into positions that enhance their ability to catalyze the rxn
For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.
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40. Substrate Active site Enzyme Enzyme-substrate complex (a) (b)
Fig. 8-16
Substrate
Active site
Figure 8.16 Induced fit between an enzyme and its substrate
Enzyme
Enzyme-substrate
complex
(a)
(b)

41. Catalysis in the Enzyme’s Active Site
In an enzymatic rxn, 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
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42. 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

43. Effects of Local Conditions on Enzyme Activity
An enzyme’s activity can be affected by
Environmental factors, such as temperature and pH
Chems that specifically influence the enzyme
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44. Effects of Temperature and pH
Each ξ has an optimal temperature and optimal pH in which it can fxn
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45. 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

46. Cofactors-nonprotein ξ helpers
inorganic or organic
Coenzyme (Coξ) if organic
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47. Enzyme Inhibitors Substrate Active site Competitive inhibitor Enzyme
Fig. 8-19
Enzyme Inhibitors
Substrate
Active site
Competitive
inhibitor
Enzyme
Figure 8.19 Inhibition of enzyme activity
Noncompetitive inhibitor
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition

48. Concept 8.5: Regulation of enzyme activity helps control metabolism
Prevents chemical chaos in the cells
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49. Allosteric Regulation of Enzymes
Allosteric regulation will inhibit or stimulate an ξ’s activity
an activator stabilizes the active form of the ξ
an inhibitor stabilizes the inactive form of the ξ
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50. 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

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

52. 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
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53. Fig. 8-22
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 no
longer binds
threonine;
pathway is
switched off.
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Figure 8.22 Feedback inhibition in isoleucine synthesis
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)