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

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

3. I. Metabolism
The totality of an organism’s chemical reactions

4. Begins with a specific molecule and ends with a product
II. Metabolic Pathways
Begins with a specific molecule and ends with a product
Each step is catalyzed by a specific enzyme
Enzyme 1
Enzyme 2
Enzyme 3 D C B A

5. Catabolic pathways: release energy, break down molecules
Ex. Cellular respiration - breakdown of glucose with oxygen

6. Anabolic pathways: consume energy, build complex molecules
Ex. Synthesis of protein from amino acids

7. III. Forms of Energy (E) Energy = capacity to cause change
Kinetic E = E from motion
Heat (thermal E) = KE from random movement of atoms or molecules
Potential E = E because of location or structure
Chemical E = PE available for release in a reaction
Energy can be converted from one form to another

8. 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.

9. IV. The Laws of Energy Transformation
Thermodynamics = the study of energy transformations
Closed system = isolated from surroundings
Open system = energy and matter can be transferred between system and surroundings
Organisms = open systems

10. A. The First Law of Thermodynamics
Energy of the universe is constant:
– Energy can be transferred and transformed, but it cannot be created or destroyed
Principle of conservation of energy

11. B. The Second Law of Thermodynamics
During every energy transfer or transformation, some energy is unusable, and is lost as heat
– Every energy transfer or transformation increases the entropy (disorder) of the universe
Chemical
energy
Heat
CO2
H2O

12. V. Free-Energy Change, G
Free energy = available energy to do work when temp and pressure are uniform

13. Change in free energy (∆G) during a process is related to the change in enthalpy (change in total energy (∆H)), change in entropy (disorder (∆S)), and temp in Kelvin (T):
∆G = ∆H – T∆S
Only processes with a negative ∆G are spontaneous and can be harnessed to do work
Free Energy Bozeman

14. VI. Free Energy and Metabolism
Exergonic reaction proceeds with a net release of free energy (ΔG < 0) and is spontaneous
Endergonic reaction absorbs free energy from its surroundings (ΔG > 0) and is nonspontaneous

15. 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

16. A. 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

17. (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

18. (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

19. (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

20. VIII. Structure and Hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP = ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
ATP Overview - Bozeman
For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.

21. Bonds between the phosphate groups can be broken by hydrolysis (releasing energy)
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.

22. 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)

23. X. How ATP Performs Work
ATP powers 3 types of cellular work (mechanical, transport, and chemical)
Energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction (energy coupling)
Overall, coupled reactions are exergonic
ATP drives endergonic reactions by transferring a phosphate group to some other molecule (phosphorylation)

24. ∆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

25. 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

26. XI. The Regeneration of ATP
ATP is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
The energy comes from catabolic reactions in the cell
The chemical PE temporarily stored in ATP drives most cellular work

27. + 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

28. XII. Activation Energy
Initial E needed to start a chemical reaction is the free energy of activation, or activation energy (EA)
Activation energy is often supplied from heat

29. 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

30. XIII. Enzymes Lower the EA
Enzymes catalyze reactions by lowering the EA
Enzymes do not affect the change in free energy (∆G); they hasten reactions that would occur eventually

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

33. 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)

34. XV. Enzyme’s Active Site
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. 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. XVI. Effects on Enzyme Activity
An enzyme’s activity can be affected by
Each enzyme has optimum Temp and pH
Chemicals that influence the enzyme (cofactors and inhibitors)

37. 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

38. A. Cofactors
Nonprotein enzyme helpers
May be inorganic (such as a metal in ionic form) or organic
Coenzyme = organic cofactor (vitamins)

39. B. Enzyme Inhibitors
Competitive inhibitors bind to active site of enzyme, competing w/ substrate
Noncompetitive inhibitors bind to another part of enzyme, causing enzyme to change shape and making active site less effective
Ex. toxins, poisons, pesticides, and antibiotics

40. 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

41. XVII. Allosteric Regulation of Enzymes
Allosteric regulation = inhibit or stimulate an enzyme’s activity
Occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site

42. A Allosteric Activation and Inhibition
Most allosterically regulated enzymes are made from polypeptide subunits
Each enzyme has active (activator stabilizes) and inactive (inhibitor stabilizes) forms

43. 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

44. Cooperativity = form of allosteric regulation that can amplify enzyme activity
Binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits

45. (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

46. B. Feedback Inhibition
End product of a metabolic pathway shuts down the pathway
Prevents cell from wasting chemical resources by making more product than needed
Biochemical Pathway (no inhibition)
Feedback Inhibition of Biochemical Pathways

47. 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)