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
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3. Fig. 8-1
Figure 8.1 What causes the bioluminescence in these fungi?

4. Metabolism is the totality of an organism’s chemical reactions
Question 1 & 2 – Define metabolism. What is a metabolic pathway? Draw a representation of one.
Metabolism is the totality of an organism’s chemical reactions
A metabolic pathway begins with a specific molecule and ends with a product
Each step is catalyzed by a specific enzyme
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5. Fig. 8-UN1
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting
molecule
Product
If for any reason one of these enzymes isn’t functioning correctly, the entire pathway shuts down

6. Question 3 – Distinguish between catabolic and anabolic pathways.
Catabolic pathways release energy by breaking down complex molecules into simpler compounds
Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism
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7. The synthesis of protein from amino acids is an example of anabolism
Anabolic pathways consume energy to build complex molecules from simpler ones
The synthesis of protein from amino acids is an example of anabolism
Bioenergetics is the study of how organisms manage their energy resources
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8. Question 4 – Define the following:
Energy is the capacity to cause change
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
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9. 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.

10. Thermodynamics is the study of energy transformations
Question 5 – Describe the first and second laws of thermodynamics. Try to relate them
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
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11. 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, but it cannot be created or destroyed
The first law is also called the principle of conservation of energy
By converting sunlight to chemical energy, a plant acts as an energy transformer, not an energy producer.
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12. The Second Law of Thermodynamics
During every energy transfer or transformation, some energy is unusable, and is often lost as heat
According to the second law of thermodynamics:
– Every energy transfer or transformation increases the entropy (disorder) of the universe
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13. (a) First law of thermodynamics (b) Second law of thermodynamics
Fig. 8-3
Heat
CO2 +
Chemical
energy
H2O
(a) First law of thermodynamics
(b) Second law of thermodynamics
Figure 8.3 The two laws of thermodynamics

14. Living cells unavoidably convert organized forms of energy to heat
Question 6
Living cells unavoidably convert organized forms of energy to heat
Cells create ordered structures from less ordered materials
Energy flows into an ecosystem in the form of light and exits in the form of heat
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15. Question 7 – Distinguish between exergonic and endergonic reactions.
Free energy is the portion of a system’s energy that can perform work.
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
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16. Progress of the reaction
Fig. 8-6
Reactants
Amount of
energy
released
(∆G < 0)
Energy
Free energy
Products
Progress of the reaction
(a) Exergonic reaction: energy released
Products
Amount of
energy
required
(∆G > 0)
Figure 8.6 Free energy changes (ΔG) in exergonic and endergonic reactions
Energy
Free energy
Reactants
Progress of the reaction
(b) Endergonic reaction: energy required

17. A cell does three main kinds of work: Chemical Transport Mechanical
Question 8 – List and describe the three kinds of work performed by a cell.
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
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18. ATP (adenosine triphosphate) is the cell’s energy shuttle
Question 9 – Draw a molecule of ATP. Bonds between phosphates in a molecule of ATP are considered “high energy bonds.” What does this mean?
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.
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19. Adenine Phosphate groups Ribose Fig. 8-8
Figure 8.8 The structure of adenosine triphosphate (ATP)
Ribose

20. The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis
Bonds between phosphates in a molecule of ATP are considered high energy because energy is released from ATP when the terminal phosphate bond is broken
This is a little misleading, because the release of energy during the hydrolysis of ATP is a result of the products changing to a state of lower free energy.
For the Cell Biology Video Stick Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.
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21. 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)

22. Question 10 – Why is ATP useful to the cell?
The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP
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
Why does the hydrolysis of ATP release so much energy? All three phosphate groups are negatively charged.
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23. The recipient molecule is now phosphorylated
Question 11 – What does it mean when a molecule is “phosphorylated?”
ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant
The recipient molecule is now phosphorylated
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24. 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

25. A muscle cell recycles its entire pool of ATP in less than one minute.
Question 12 – Note the ATP cycle. How often does a muscle cell turnover its entire supply of ATP?
ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
The energy to phosphorylate ADP comes from catabolic reactions in the cell
A muscle cell recycles its entire pool of ATP in less than one minute.
This represents 10 million molecules of ATP consumed and regenerated per second per cell. WOW!
If it weren’t for this ATP cycle, humans would use up their entire body weight in ATP each day.
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26. + H2O Energy for cellular work (endergonic, energy-consuming
Fig. 8-12
ATP +
H2O
Energy from
catabolism (exergonic,
energy-releasing
processes)
Energy for cellular
work (endergonic,
energy-consuming
processes)
Figure 8.12 The ATP cycle
ADP + P i

27. Other examples: catalase, alcohol dehydrogenase
Question 13 – What is an enzyme? Why are they important to our cells and ultimately to us?
A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction
An enzyme is a catalytic protein whose function is completely dependent on its 3-d shape
Enzymes do not make reactions occur that wouldn’t normally happen, they just speed them up
Enzyme are not used up in a reaction, but rather can keep catalyzing further reactions.
Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction
Other examples: catalase, alcohol dehydrogenase
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28. 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)

29. Enzymes catalyze reactions by lowering the EA barrier
Question 14 – What is activation energy? What effect does an enzyme have on activation energy?
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
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
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30. 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

31. 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

32. Question 15 – How do enzymes lower the activation energy barrier?
In biological systems, heat is able to speed up reactions by allowing reactants to attain the transition state more often, but this can be bad.
First, high temps denature proteins and kills cells.
Second, heat would speed up all reactions, not just those that are needed.
Organisms therefore use an alternative: catalysis.
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33. Question 15 – How do enzymes lower the activation energy barrier?
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
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34. Question 16 – define the following:
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
For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.
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35. 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

36. No, enzymes cannot catalyze a variety of reactions.
Question 17 – Can a specific enzyme catalyze a variety of reactions on a variety of substrates?
No, enzymes cannot catalyze a variety of reactions.
Their active site will accommodate only a specific substrate.

37. Direct participation of the active site in the chemical reaction.
Question 18 – Describe the ways that an enzyme lowers activation energy and speeds up reactions.
The active site provides a template on which the substrates can come together in the proper orientation for a Rx to occur;
An enzyme may stretch the substrate molecules toward their transition-state form;
The active site may provide a microenvironment that is more conducive to particular reaction
Direct participation of the active site in the chemical reaction.
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38. An enzyme’s activity can be affected by
Question 19 – Describe the effects of temperature and pH on enzyme activity.
An enzyme’s activity can be affected by
General environmental factors, such as temperature, salinity and pH
Each enzyme has an optimal temperature in which it can function
Each enzyme has an optimal pH in which it can function
Ex: PCR enzyme
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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. Question 20 – Distinguish between cofactors and coenzymes.
Cofactors are nonprotein enzyme helpers
Cofactors may be inorganic (such as a metal in ionic form) or organic
An organic cofactor is called a coenzyme
Coenzymes include vitamins
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41. Question 21 – Distinguish between competitive and noncompetiti
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
Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
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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. Question 22 – What is allosteric regulation
Question 22 – What is allosteric regulation? Use the ATP example from page 157 to explain your answer.
Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes
Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
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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
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45. Figure 8.20 Allosteric regulation of enzyme activity
Allosteric enyzme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Oscillation
Non-
functional
active
site
Inhibitor
Inactive form
Stabilized inactive
form
Figure 8.20 Allosteric regulation of enzyme activity
(a) Allosteric activators and inhibitors
Substrate
Inactive form
Stabilized active
form
(b) Cooperativity: another type of allosteric activation

46. 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
Substrate
Figure 8.20b Allosteric regulation of enzyme activity
Inactive form
Stabilized active
form
(b) Cooperativity: another type of allosteric activation

47. Question 23 – Describe 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
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48. 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)

49. 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
In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria
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50. 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
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51. 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
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