1. Chapter 8: An introduction to Metabolism

2. Start Your Engines Is a living organism an open or closed system?
Explain your answer.

3. Metabolism Metabolism in the living cell
Miniature factory where thousands of reactions or energy conversions occur
Energy
Free energy
Energy in Biological systems
ATP
Enzymes
Function
Regulation

4. Explain the concept of energy coupling in the of biological system.
Starter.
Explain the concept of
energy coupling in the
of biological system.
(hint: think ATP)

5. Metabolism What is Metabolism
The totality of an organisms chemical reactions.

6. Metabolism
Energy Conversion is not 100%
Metabolism transforms matter and energy, subject to the laws of thermodynamics
Energy can be transferred and
transformed but NOT destroyed
2. Every energy transformation
Increases the entropy in the universe.

7. Metabolic Pathways Metabolism is Controlled
Metabolism occurs in pathways sometimes with many steps.
Begins w/ specific molecule, ends w/ product
Each step catalyzed by specific enzyme
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting molecule
Product

8. Proteins Amino Acids Metabolism Catabolic pathways
Complex molecules  simpler compounds
Release energy
Proteins
Amino Acids

9. Metabolism Anabolic pathways
Build complicated molecules from simpler ones
Consume energy

10. Energy can be converted from one form to another
On the platform, a diver
has more potential energy.
Diving converts potential
energy to kinetic energy.
Climbing up converts kinetic
energy of muscle movement
to potential energy.
In the water, a diver has
less potential energy.
Figure 8.2
Kinetic
Potential
Chemical
Thermal

11. Energy in a Biological System
Energy conversion
Chemical
energy

12. The Second Law of Thermodynamics
Spontaneous changes increase the entropy, or disorder, of the universe
Heat
co2
H2O +
Energy Conversion is not 100%

13. Energy Living systems Increase entropy of the universe
Use energy to maintain order
50µm
Figure 8.4

14. Free-Energy Change, G
Determines if reaction occurs spontaneously

15. ∆Free energy= ∆(Enthalpy) – T∆(Entropy) Negative ∆G= Spontaneous
Change in free energy, ∆G during a biological process
Related directly to the enthalpy (total energy of a system ∆H) change and the change in entropy
∆G = ∆H – T∆S
∆Free energy= ∆(Enthalpy) – T∆(Entropy)
Negative ∆G= Spontaneous
Positive ∆G = Requires energy

16. (a) Exergonic reaction: energy released
Net release of free E, spontaneous
Figure 8.6
Reactants
Products
Energy
Progress of the reaction
Amount of
energy
released (∆G <0)
Free energy
(a) Exergonic reaction: energy released

17. (b) Endergonic reaction: energy required
Absorbs free E from surroundings, nonspontaneous
Figure 8.6
Energy
Products
Amount of
energy
released (∆G>0)
Reactants
Progress of the reaction
Free energy
(b) Endergonic reaction: energy required

18. Energy in a Biological Systems
Maximum stability  system at equilibrium
Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. .
Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed.
Gravitational motion. Objects
move spontaneously from a
higher altitude to a lower one.
More free energy (higher G)
Less stable
Greater work capacity
Less free energy (lower G)
More stable
Less work capacity
In a spontaneously change
The free energy of the system decreases (∆G<0)
The system becomes more stable
The released free energy can
be harnessed to do work
(a)
(b)
(c)
Figure 8.5 

19. Metabolic pathways as systems: Closed System
Reactions in a closed system eventually reach equilibrium
∆G < 0
∆G = 0

20. Cells constant flow of materials in and out, do not reach equilibrium
Open System
Cells constant flow of materials in and out, do not reach equilibrium
∆G < 0

21. Multi-Step Open System
Analogy for cellular respiration
∆G < 0
Holy Exergonic Reactions
Batman!

22. ATP Cellular Energy Currency
(adenosine triphosphate)
Cell’s Energy shuttle. ATP powers cellular work by coupling exergonic reactions to endergonic reactions
Figure 8.8 O
CH2 H OH N C HC
NH2
Adenine
Ribose
Phosphate groups - CH

23. ATP
E released from ATP when terminal phosphate bond is broken (hydrolysis)
Figure 8.9 P
Adenosine triphosphate (ATP)
H2O +
Energy
Inorganic phosphate
Adenosine diphosphate (ADP)
P i

24. ATP Must look at total ∆G
ATP hydrolysis coupled to other reactions
Endergonic reaction: ∆G is positive, reaction
is not spontaneous
∆G = +3.4 kcal/mol
Glu
∆G = kcal/mol
ATP
H2O +
NH3
ADP
NH2
Glutamic
acid
Ammonia
Glutamine
Exergonic reaction: ∆ G is negative, reaction
is spontaneous P
Coupled reactions: Overall ∆G is negative;
together, reactions are spontaneous
∆G = –3.9 kcal/mol

25. Cellular work powered by hydrolysis of ATP
(c) Chemical work: ATP phosphorylates key reactants P
Membrane
protein
Motor protein
P i
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
ATP
(b) Transport work: ATP phosphorylates transport proteins
Solute
transported
Glu
NH3
NH2 +
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made
ADP

26. Regeneration of ATP Energy from Food!!
Catabolic pathways: ATP from ADP and phosphate (ATP Synthesis)
ATP synthesis from
ADP + P i requires energy
ATP
ADP + P i
Energy for cellular work
(endergonic, energy-
consuming processes)
Energy from catabolism
(exergonic, energy yielding
processes)
ATP hydrolysis to
ADP + P i yields energy
Figure 8.12

28. Proteins, speed up metabolic reactions by lowering E barriers
Enzymes
Proteins, speed up metabolic reactions by lowering E barriers
Catalyst: speeds up a reaction w/o being consumed by the reaction
Proximity

29. Enzymes Substrate Enzyme Reactant an enzyme acts on
Binds to substrate, forming enzyme-substrate complex
Complex
Substrate
Enzyme

30. Enzymes Lower the EA Barrier
Activation energy, EA Initial amount of E needed to start a chemical reaction. Often in the form of heat
Progress of the reaction
Products
Course of
reaction
without
enzyme
Reactants
with enzyme EA
EA with
is lower
∆G is unaffected
by enzyme
Free energy
Figure 8.15
Even w/
-∆G reaction
may be too
slow biologically

31. How Enzymes Work Active site
Region on enzyme where the substrate binds
Figure 8.16
Substate
Active site
Enzyme
(a)

32. Induced fit of substrate
substrate in positions that enhance catalysis
Figure 8.16
(b)
Enzyme- substrate
complex
Can be multiple
active sites

33. Catalytic cycle of an enzyme
Conformational change
Substrates
Products
Enzyme
Enzyme-substrate
complex
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 Active site (and R groups of
its amino acids) can lower EA
and speed up a reaction by
• acting as a template for
substrate orientation,
• stressing the substrates
and stabilizing the
transition state,
• providing a favorable
microenvironment,
• participating directly in the
catalytic reaction.
4 Substrates are
Converted into
Products.
5 Products are
Released.
1 6 Active site
Is available for
two new substrate
Mole.
Figure 8.17

34. (a) Optimal temperature for two enzymes
Enzymes have optimal conditions in which they function
Figure 8.18
Optimal temperature for
enzyme of thermophilic
Rate of reaction 20 40 80
100
Temperature (Cº)
(a) Optimal temperature for two enzymes
typical human enzyme
(heat-tolerant)
bacteria
Temp pH

35. Enzymes Cofactors Coenzymes Nonprotein enzyme helper Organic cofactors
Cu+, Mg2+, Mn2+
Coenzymes
Organic cofactors
NAD, FAD, vitamins

36. Enzyme Regulation
Regulation of enzyme activity controls metabolism
Cell’s metabolic pathways tightly regulated

37. Enzyme Regulation: Competitive inhibitors
Bind to active site, compete w/ substrate
Figure 8.19
(b) Competitive inhibition
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Competitive
inhibitor
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
(a) Normal binding

38. Enzyme regulation: Noncompetitive inhibitors
Bind to another part of enzyme, changing function
Figure 8.19
A noncompetitive
inhibitor binds to the
enzyme away from
the active site, altering
the conformation of
the enzyme so that its
active site no longer
functions.
Noncompetitive inhibitor
(c) Noncompetitive inhibition

39. Enzyme Regulation: Allosteric
Protein’s function at one site is affected by binding of a regulatory molecule at another site
Stabilized inactive form
Allosteric activater stabilizes active from
Allosteric enyzme with four subunits
Active site (one of four)
Regulatory site (one of four)
Active form
Activator
Stabilized active form
Allosteric inactivater stabilizes inactive form
Inhibitor
Inactive form
Non- functional active site
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.
Oscillation
Figure 8.20

40. Enzyme regulation: Cooperativity
Cooperativity; allosteric regulation that amplifies enzyme activity
Figure 8.20
Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation.
Substrate
Inactive form
Stabilized active form
(b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate.

41. Enzyme Regulation: Feedback Inhibition
End product of metabolic pathway shuts down pathway
Active site available
Isoleucine used up by cell
Feedback inhibition
Isoleucine binds to allosteric site
Active site of enzyme 1 no longer binds threonine; pathway is switched off
Initial substrate (threonine)
Threonine in active site
Enzyme 1 (threonine deaminase)
Intermediate A
Intermediate B
Intermediate C
Intermediate D
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5
End product (isoleucine)
Figure 8.21