1. 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
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2. The Structure and Hydrolysis of ATP
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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3. Adenine Phosphate groups Ribose Fig. 8-8
Figure 8.8 The structure of adenosine triphosphate (ATP)
Ribose

4. Energy 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
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
For the Cell Biology Video Stick Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.
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5. 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)

6. Overall, the coupled reactions 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 energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction
Overall, the coupled reactions are exergonic
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7. The recipient molecule is now 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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8. 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

9. The Regeneration 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
The chemical potential energy temporarily stored in ATP drives most cellular work
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10. + 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

11. An enzyme is a catalytic protein
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
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12. 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)

13. 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
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14. 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

15. 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
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16. 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

17. 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
For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.
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18. 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)

19. 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
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20. Substrates enter active site; enzyme
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

21. 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
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22. 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
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23. 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

24. 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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25. 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
Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
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26. 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

27. Concept 8.5: Regulation of enzyme activity helps control metabolism
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
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28. Allosteric Regulation 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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29. 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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30. Fig. 8-20 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

31. 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

32. 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
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33. (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

34. 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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35. Fig. 8-22 Initial substrate (threonine) Active site available
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
Figure 8.22 Feedback inhibition in isoleucine synthesis
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)

36. 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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37. 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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