Energy, Enzymes, and Metabolism.ppt

1. Energy, Enzymes, and
Metabolism
NADEEM AHMED Ph.D

2. Energy, Enzymes, and Metabolism
• What Physical Principles Underlie
Biological Energy Transformations?
• What Is the Role of ATP in Biochemical
Energetics?
• What Are Enzymes?
• How Do Enzymes Work?
• How Are Enzyme Activities Regulated?

3. What Physical Principles Underlie Biological Energy
Transformations?
The transformation of energy is a
hallmark of life.
Energy is the capacity to do work, or the
capacity for change.
Energy transformations are linked to
chemical transformations in cells.

4. 8.1 What Physical Principles Underlie Biological Energy
Transformations?
All forms of energy can be placed in two
categories:
• Potential energy is stored energy—as
chemical bonds, concentration gradient,
charge imbalance, etc.
• Kinetic energy is the energy of
movement

5. What Physical Principles Underlie Biological Energy
Transformations?
The laws of thermodynamics (thermo,
“energy”; dynamics, “change”) apply to all
matter and all energy transformations in
the universe.
They help us to understand how cells
harvest and transform energy to sustain
life.

6. What Physical Principles Underlie Biological Energy
Transformations?
First law of thermodynamics: Energy is
neither created nor destroyed.
When energy is converted from one form
to another, the total energy before and
after the conversion is the same.

7. What Physical Principles Underlie Biological Energy
Transformations?
Second law of thermodynamics: When
energy is converted from one form to
another, some of that energy becomes
unavailable to do work.
No energy transformation is 100 percent
efficient.

8. Figure The Laws of Thermodynamics

9. What Physical Principles Underlie Biological Energy
Transformations?
Entropy is a measure of the disorder in a
system.
It takes energy to impose order on a
system. Unless energy is applied to a
system, it will be randomly arranged or
disordered.

10. What Physical Principles Underlie Biological Energy
Transformations?
In any system:
Total energy = usable energy + unusable energy
enthalpy (H) = free energy (G) + entropy (S)
or H = G + TS (T = absolute temperature)
G = H – TS

11. What Physical Principles Underlie Biological Energy
Transformations?
Change in energy can be measured in
calories or joules.
Change in free energy (ΔG) in a reaction
is the difference in free energy of the
products and the reactants.

12. What Physical Principles Underlie Biological Energy
Transformations?
ΔG = ΔH – TΔS
• If ΔG is negative, free energy is
released
• If ΔG is positive, free energy is
consumed
If free energy is not available, the
reaction does not occur.

13. What Physical Principles Underlie Biological Energy
Transformations?
Magnitude of ΔG depends on:
• ΔH—total energy added (ΔH > 0) or
released (ΔH < 0)
• ΔS—change in entropy. Large changes
in entropy make ΔG more negative

14. What Physical Principles Underlie Biological Energy
Transformations?
If a chemical reaction increases entropy,
the products will be more disordered.
Example: In hydrolysis of a protein into its
component amino acids, ΔS is positive.

15. What Physical Principles Underlie Biological Energy
Transformations?
Second law of thermodynamics:
Disorder tends to increase because of
energy transformations.
Living organisms must have a constant
supply of energy to maintain order.

16. What Physical Principles Underlie Biological Energy
Transformations?
Metabolism: Sum total of all chemical
reactions in an organism.
Anabolic reactions: Complex molecules
are made from simple molecules; energy
input is required.
Catabolic reactions: Complex molecules
are broken down to simpler ones and
energy is released.

17. What Physical Principles Underlie Biological Energy
Transformations?
Exergonic reactions release free energy
(–ΔG): Catabolism; complexity
decreases (generates disorder).
Endergonic reactions consume free
energy (+ΔG): anabolism; complexity
(order) increases.

18. Figure Exergonic and Endergonic Reactions

19. Figure 8.3 Exergonic and Endergonic Reactions (Part 2)

20. 8.1 What Physical Principles Underlie Biological Energy
Transformations?
In principle, chemical reactions can run in
both directions.
At chemical equilibrium, ΔG = 0
Forward and reverse reactions are
balanced.
The concentrations of A and B determine
which direction will be favored.
B
A 

21. What Physical Principles Underlie Biological Energy
Transformations?
Every reaction has a specific equilibrium
point.
ΔG is related to the point of equilibrium:
The further towards completion the point
of equilibrium is, the more free energy is
released.
ΔG values near zero are characteristic of
readily reversible reactions.

22. Figure 8.4 Chemical Reactions Run to Equilibrium

23. 8.2 What Is the Role of ATP in Biochemical Energetics?
ATP (adenosine triphosphate) captures
and transfers free energy.
ATP releases a large amount of energy
when hydrolyzed.
ATP can phosphorylate, or donate
phosphate groups to other molecules.

24. 8.2 What Is the Role of ATP in Biochemical Energetics?
ATP is a nucleotide.
Hydrolysis of ATP yields free energy.
ΔG = –7.3 to –14 kcal/mol
(exergonic)
energy
free
P
ADP
O
H
ATP i 


 2

25. Figure 8.5 ATP (Part 1)

26. 8.2 What Is the Role of ATP in Biochemical Energetics?
Bioluminescence is an endergonic
reaction driven by ATP hydrolysis:
light
PP
AMP
in
oxylucifer
ATP
O
luciferin
i
luciferase





 


 2

27. Figure 8.5 ATP (Part 2)

28. What Is the Role of ATP in Biochemical Energetics?
The formation of ATP is endergonic:
Formation and hydrolysis of ATP couples
exergonic and endergonic reactions.
O
H
ATP
energy
free
P
ADP i 2





29. Energy Coupling
• Living organisms have the ability to couple
exergonic and endergonic reactions:
• Energy released by exergonic reactions is
captured and used to make ATP from ADP and Pi
• ATP can be broken back down to ADP and Pi,
releasing energy to power the cell’s endergonic
reactions.

30. Figure Coupling of Reactions
Exergonic and endergonic reactions are coupled.

31. Activation Energy
• All reactions, both endergonic and exergonic, require an input of energy
to get started. This energy is called activation energy
• The activation energy, EA
 Is the initial amount of energy needed to start a chemical reaction
 Activation energy is needed to bring the reactants close together and
weaken existing bonds to initiate a chemical reaction.
 Is often supplied in the form of heat from the surroundings in a system.
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Free
energy
Progress of the reaction
∆G < O
EA
A B
C D
Reactants
A
C D
B
Transition state
A B
C D
Products

32. What Are Enzymes?
Catalysts speed up the rate of a reaction.
The catalyst is not altered by the
reactions.
Most biological catalysts are enzymes
(proteins) that act as a framework in
which reactions can take place.

33. What Are Enzymes?
Some reactions are slow because of an
energy barrier—the amount of energy
required to start the reaction, called
activation energy (Ea).

34. Figure Activation Energy Initiates Reactions (Part 1)

35. Figure Activation Energy Initiates Reactions (Part 2)

36. What Are Enzymes?
Activation energy changes the reactants
into unstable forms with higher free
energy—transition state intermediates.
Activation energy can come from heating
the system—the reactants have more
kinetic energy.
Enzymes and ribozymes lower the energy
barrier by bringing the reactants together.

37. What Are Enzymes?
Biological catalysts (enzymes and
ribozymes) are highly specific.
Reactants are called substrates.
Substrate molecules bind to the active
site of the enzyme.
The three-dimensional shape of the
enzyme determines the specificity.

38. Figure Enzyme and Substrate

39. What Are Enzymes?
The enzyme-substrate complex (ES) is
held together by hydrogen bonds,
electrical attraction, or covalent bonds.
E + S → ES → E + P
The enzyme may change when bound to
the substrate, but returns to its original
form.

40. What Are Enzymes?
Enzymes lower the energy barrier for
reactions.
The final equilibrium doesn’t change, and
ΔG doesn’t change.

41. Figure Enzymes Lower the Energy Barrier

42. How Do Enzymes Work?
In catalyzing a reaction, an enzyme may
use one or more mechanisms.

43. Figure Life at the Active Site (A)
Enzymes orient substrate molecules,
bringing together the atoms that will bond.

44. Figure Life at the Active Site (B)
Enzymes can stretch the bonds in substrate
molecules, making them unstable.

45. Figure Life at the Active Site (C)
Enzymes can temporarily add chemical
groups to substrates.

46. How Do Enzymes Work?
Acid-base catalysis: Enzyme side chains
transfer H+ to or from the substrate,
causing a covalent bond to break.
Covalent catalysis: A functional group in
a side chain bonds covalently with the
substrate.
Metal ion catalysis: Metals on side chains
loose or gain electrons.

47. How Do Enzymes Work?
Shape of enzyme active site allows a
specific substrate to fit (lock and key).
Binding of substrate to the active site
depends on hydrogen bonds, attraction
and repulsion of electrically charged
groups, and hydrophobic interactions.
Many enzymes change shape when they
bind to the substrate—induced fit.

48. How Do Enzymes Work?
Some enzymes require “partners”:
• Prosthetic groups: Non-amino acid
groups bound to enzymes
• Cofactors: Inorganic ions
• Coenzymes: Small carbon-containing
molecules; not bound permanently to
enzymes

50. How Do Enzymes Work?
The rate of a catalyzed reaction depends
on substrate concentration.
Concentration of an enzyme is usually
much lower than concentration of a
substrate.
At saturation, all enzyme is bound to
substrate—maximum rate.

51. Figure Catalyzed Reactions Reach a Maximum Rate

52. How Do Enzymes Work?
Maximum rate is used to calculate
enzyme efficiency: Molecules of
substrate converted to product per unit
time (turnover).
Ranges from 1 to 40 million molecules
per second!

53. How Are Enzyme Activities Regulated?
Inhibitors regulate enzymes: Molecules
that bind to the enzyme and slow
reaction rates.
Naturally occurring inhibitors regulate
metabolism.

54. How Are Enzyme Activities Regulated?
Irreversible inhibition: Inhibitor
covalently bonds to side chains in the
active site—permanently inactivates the
enzyme.
Example: DIPF or nerve gas
Diisopropyl fluorophosphate

55. Figure Irreversible Inhibition

56. How Are Enzyme Activities Regulated?
Reversible inhibition: Inhibitor bonds
noncovalently to the active site and
prevents substrate from binding.
Competitive inhibitors compete with the
natural substrate for binding sites.
When concentration of competitive
inhibitor is reduced, it detaches from the
active site.

57. Figure Reversible Inhibition (A)

58. 8.5 How Are Enzyme Activities Regulated?
Noncompetitive inhibitors: Bind to the
enzyme at a different site (not the active
site).
The enzyme changes shape and alters
the active site.

59. Figure Reversible Inhibition (B)

60. How Are Enzyme Activities Regulated?
Allostery (allo, “different”; stereos,
“shape”)
Some enzymes exist in more than one
shape:
• Active form—can bind substrate
• Inactive form—cannot bind substrate but
can bind an inhibitor

61. How Are Enzyme Activities Regulated?
Most allosteric enzymes are proteins with
quaternary structure.
Active site is on the catalytic subunit.
Inhibitors and activators bind to the
regulatory subunits.

62. Figure Allosteric Regulation of Enzymes

63. How Are Enzyme Activities Regulated?
Within a certain range, reaction rates of
allosteric enzymes are sensitive to small
changes in substrate concentration.

64. Figure 8.18 Allostery and Reaction Rate

65. How Are Enzyme Activities Regulated?
Allosteric enzymes are very sensitive to
low concentrations of inhibitors, and are
important in regulating metabolic
pathways.

66. How Are Enzyme Activities Regulated?
Metabolic pathways:
The first reaction is the commitment
step—other reactions then happen in
sequence.
Feedback inhibition (end-product
inhibition): The final product acts as a
noncompetitive inhibitor of the first
enzyme, which shuts down the pathway.

67. Figure 8.19 Feedback Inhibition of Metabolic Pathways

68. 8.5 How Are Enzyme Activities Regulated?
Every enzyme is most active at a
particular pH.
pH influences the ionization of functional
groups.
Example: at low pH (high H+) —COO–
may react with H+ to form —COOH
which is no longer charged; this affects
folding and thus enzyme function.

69. Figure 8.20 pH Affects Enzyme Activity

70. 8.5 How Are Enzyme Activities Regulated?
Every enzyme has an optimal
temperature.
At high temperatures, noncovalent bonds
begin to break.
Enzyme can lose its tertiary structure and
become denatured.

71. Figure 8.21 Temperature Affects Enzyme Activity

72. 8.5 How Are Enzyme Activities Regulated?
Isozymes: Enzymes that catalyze the
same reaction but have different
properties, such as optimal temperature.
Organisms can use isozymes to adjust to
temperature changes.
Enzymes in humans have higher optimal
temperature than enzymes in most
bacteria—a fever can denature the
bacterial enzymes.