1. An Introduction to Metabolism6
An Introduction to Metabolism

2. All living organisms require a constant supply of energy for organization, growth, and reproduction.

3. Concept 6.1: An organism’s metabolism transforms matter and energy
Metabolism - totality of an organism’s chemical reactions
In other words, all of the chemical reactions occurring within an individual
Each step is catalyzed by an enzyme
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4. Enzyme 1 Enzyme 2 Enzyme 3 Product Starting molecule A B C D
Figure 6.UN01
Enzyme 1
Enzyme 2
Enzyme 3
Product
Starting
molecule A B C D
Reaction 1
Reaction 2
Reaction 3
Figure 6.UN01 In-text figure, metabolic pathway schematic, p. 116 4

5. Two Types of Metabolic Pathways:
Catabolic
Anabolic

6. Ex. Cellular respiration
Catabolic pathways release energy by breaking down complex molecules into simpler molecules
Energy is released (that can be used to do work)
Ex. Cellular respiration
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7. Where does the usable energy come from?
It is NOT the breaking of bonds that releases energy It is the energy that is released after bonds are broken (of the reactants) and new bonds (of the product with simpler molecules) form that can be used

8. Anabolic pathways consume energy to build complex molecules from simpler ones
Energy is consumed
Ex. Photosynthesis
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10. Forms of Energy: A Brief Review
Energy: capacity to cause change
ability to do work

11. Kinetic Energy: energy of motion
Thermal energy: KE associated with the random movement of atoms or electrons (heat=transfer of TE)
Potential Energy: energy that matter possesses because of its location or structure
Chemical energy: PE available for release in a chemical reaction

12. Conversion Between KE and PE:

13. A diver has more potential energy on the platform.
Figure 6.2
Diving converts
potential energy to
kinetic energy.
A diver has more potential
energy on the platform.
Figure 6.2 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. 13

14. What do you know about energy?

15. Laws of Energy Transformation
First Law of Thermodynamics: energy cannot be created or destroyed, only transferred or transformed
Ex. Bear eats a fish: chemical energy in the organic molecules is converted to kinetic and other forms of energy as it carries out biological processes

16. (a) First law of thermodynamics (b) Second law of thermodynamics
Figure 6.3
Heat
Chemical
energy
Figure 6.3 The two laws of thermodynamics
(a) First law of thermodynamics
(b) Second law of thermodynamics 16

17. Entropy: a measure of disorder or randomness
Second Law of Thermodynamics: every energy transfer increases the entropy of the universe
Entropy: a measure of disorder or randomness
With each energy transfer or transformation, some energy is converted to thermal energy and released as heat
Cannot perform work, lends to the entropy (disorder) of the universe!!!!!

18. There is a natural tendency to go move from order to disorder
Analogy:
Other examples?

19. Spontaneous process: (energetically favorable) a process that occurs without an input of energy
For a process to occur on its own, it must increase the entropy of the universe
Nonspontaneous process requires the input of energy

21. Free-Energy Change (G), Stability, and Equilibrium
A living system’s free energy is energy that can do work when temperature and pressure are uniform
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22. ∆G = Gfinal state – Ginitial state
The change in free energy (∆G) is the difference between the free energy of the final state and the free energy of the initial state
∆G = Gfinal state – Ginitial state
Only processes with a negative ∆G are spontaneous
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23. Based on their free energy changes, chemical reactions can be classified as exergonic or endergonic.

24. Exergonic and Endergonic Reactions in Metabolism
An exergonic reaction
net release of free energy
Spontaneous
∆G is negative
Ex. Cellular respiration
The reactants have more free energy than the products
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25. Remember:
The usable energy comes from bonds breaking and reforming

26. Amount of energy released (G  0)
Figure 6.6a
(a) Exergonic reaction: energy released, spontaneous
Reactants
Amount of
energy
released
(G  0)
Energy
Free energy
Products
Figure 6.6a Free energy changes (ΔG) in exergonic and endergonic reactions (part 1: exergonic)
Progress of the reaction 26

27. An endergonic reaction absorbs free energy Nonspontaneous
∆G is positive
Ex. Photosynthesis
The products have more free energy than the reactants
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28. Amount of energy required (G  0)
Figure 6.6b
(b) Endergonic reaction: energy required,
nonspontaneous
Products
Amount of
energy
required
(G  0)
Energy
Free energy
Reactants
Figure 6.6b Free energy changes (ΔG) in exergonic and endergonic reactions (part 2: endergonic)
Progress of the reaction 28

30. 6.3 ATP Powers Cell Work by Coupling
Cells do 3 main types of work:
1. Chemical work
2. Transport work
3. Mechanical work

31. The coupling is usually driven by ATP hydrolysis
Cells complete work through energy coupling: the use of an exergonic process to drive an endergonic one
The coupling is usually driven by ATP hydrolysis
ATP: primary energy source for cells and energy coupling

32. The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate)
composed of
ribose (sugar),
adenine (nitrogenous base)
three phosphate groups
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33. (a) The structure of ATP
Figure 6.8a
Adenine
Phosphate groups
Ribose
Figure 6.8a The structure and hydrolysis of adenosine triphosphate (ATP) (part 1: structure)
(a) The structure of ATP 33

34. Adenosine triphosphate (ATP)
Figure 6.8b
Adenosine triphosphate (ATP)
Figure 6.8b The structure and hydrolysis of adenosine triphosphate (ATP) (part 2: hydrolysis)
Energy
Inorganic
phosphate
Adenosine diphosphate (ADP)
(b) The hydrolysis of ATP 34

35. ATP is much less stable than ADP + Pi
The reaction is exergonic and releases 7.3kcal of energy per mole of ATP hydrolyzed
-7.3kcal/mol

36. In the cell, proteins can harness the energy released during ATP hydrolysis

37. If the free energy of the endergonic reaction is less than the amount of energy released by the ATP hydrolysis (exergonic rxn), the two reactions can be coupled.
Usually involves phosphorylation: adding a phosphate group

39. Phosphorylated intermediate: the recipient with the phosphate group bonded to it

40. Concept 6.4: Enzymes speed up metabolic reactions by lowering energy barriers
An enzyme is a catalytic protein
Speeds up the reaction without being consumed
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41. Sucrose (C12H22O11) Glucose (C6H12O6) Fructose (C6H12O6)
Figure 6.UN02
Sucrase
Sucrose
(C12H22O11)
Glucose
(C6H12O6)
Fructose
(C6H12O6)
Figure 6.UN02 In-text figure, hydrolysis of sucrose, p. 125 41

42. How Enzymes Speed Up Reactions
Enzymes catalyze reactions by lowering the activation energy (EA) barrier
Activation energy: the amount of energy needed to initiate the reaction
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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43. Progress of the reaction
Figure 6.12 A B C D
Transition state A B EA
Free energy C D
Reactants A B
Figure 6.12 Energy profile of an exergonic reaction
G  0 C D
Products
Progress of the reaction 43

44. Activation Energy reactants
energy barrier with no enzyme to promote reaction
energy barrier with an enzyme’s participation
products
Fig. 6-9, p.96

45. Progress of the reaction
Figure 6.13
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 6.13 The effect of an enzyme on activation energy
Products
Progress of the reaction 45

46. Substrate Specificity of Enzymes
The reactant that an enzyme acts on is called the substrate
enzyme-substrate complex enzyme bound to substrate
active site - region on enzyme where substrate binds
Enzyme specificity results from complementary fit between active site and substrate
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48. Substrate Active site Enzyme Enzyme-substrate complex Figure 6.14
Figure 6.14 Induced fit between an enzyme and its substrate
Enzyme
Enzyme-substrate
complex 48

49. 2 Substrates are held in active site by weak interactions. 1
Figure 2
Substrates are
held in active site by
weak interactions. 1
Substrates enter
active site.
Substrates
Enzyme-substrate
complex
Active
site is
available
for new
substrates. 5
Figure The active site and catalytic cycle of an enzyme (step 5)
Enzyme
Products are
released. 4 3
Substrates are
converted to
products.
Products 49

50. Effects of Local Conditions on Enzyme Activity
An enzyme’s activity can be affected by temperature, pH and chemicals that influence the enzyme
Each enzyme has an optimal temperature & pH
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51. Optimal temperature for typical human enzyme (37C)
Figure 6.16
Optimal temperature for
typical human enzyme
(37C)
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria (77C)
Rate of reaction 20 40 60 80
100
120
Temperature (C)
(a) Optimal temperature for two enzymes
Optimal pH for pepsin
(stomach
enzyme)
Optimal pH for trypsin
(intestinal
enzyme)
Figure 6.16 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 51

52. Effect of Temperature
Fig. 6-13, p.81

53. Cofactors: ENZYME ACTIVATORS
Cofactors are inorganic non-protein enzyme helpers
Often required by the enzyme
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54. Coenzymes: Organic cofactors are called
Some coenzymes are vitamins

55. Inhibitors: Enzyme Inhibitors
Competitive inhibitors: molecule similar to the substrate binds to active site competing with substrate
Enzyme CANNOT act on inhibitor
Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape so substrate cannot bond
Ex. Specific toxins and poisons
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57. (b) Competitive inhibition (c) Noncompetitive inhibition
Figure 6.17
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive
inhibition
Substrate
Active site
Competitive
inhibitor
Enzyme
Figure 6.17 Inhibition of enzyme activity
Noncompetitive
inhibitor 57

58. Allosteric Regulation of Enzymes
Allosteric regulation - regulatory molecule binds to protein at one site and affects protein’s function at another site
may either inhibit or stimulate enzyme
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60. (a) Allosteric activators and inhibitors
Figure 6.18
(a) Allosteric activators and inhibitors
(b) Cooperativity: another type of allosteric
activation
Allosteric enzyme
with four subunits
Active site
(one of four)
Substrate
Regulatory
site (one
of four)
Activator
Active form
Stabilized
active form
Inactive form
Stabilized
active form
Oscillation
Figure 6.18 Allosteric regulation of enzyme activity
Non-
functional
active site
Inhibitor
Inactive
form
Stabilized
inactive form 60

61. Fluctuating concentrations of regulators can affect enzyme activity

62. Feedback Inhibition
In feedback inhibition, the end product of a metabolic pathway shuts down the pathway by binding to an enzyme that acts earlier in the pathway
Ex. Synthesizing isoleucine (amino acid) from threonine
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63. End product (isoleucine)
Figure 6.19
Active site available
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
Intermediate A
Feedback
inhibition
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site.
Figure 6.19 Feedback inhibition in isoleucine synthesis
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine) 63