The Working Cell

1
Chapter 8 The Working Cell
2
Cellular Metabolism

• Total of all of an organisms chemical reactions
• Anabolic pathways build complex molecules from
  smaller ones, require energy
• Catabolic pathways break down complex molecules
  into smaller ones, releasing energy

3
Fig. 8-UN1
Metabolic Pathway
Enzyme 1
Enzyme 2
Enzyme 3
D
C
B
A
Reaction 1
Reaction 3
Reaction 2
Product
Starting molecule
4
Energy

• Defined as the capacity to do work
• Two types
• Kinetic energy
• Potential energy

5
Fig. 8-2
Diving converts potential energy to kinetic
energy.
A diver has more potential energy on the
platform than in the water.
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.
6
Chemical Energy
7
Thermodynamics

• The study of energy transformation
• Two laws
• Energy cannot be created or destroyed
• Energy transformation is not 100 efficient

8
Fig. 8-3
Heat
CO2

Chemical energy
H2O
(a) First law of thermodynamics
(b) Second law of thermodynamics
9
Free Energy Concept

• Called Gibbs Free Energy
• Portion of a systems energy that is available to
  do work
• Change in free energy (?G)
• Used to determine if a process is spontaneous
• A process with a negative ?G is spontaneous

10
Fig. 8-5

• More free energy (higher G)
• Less stable
• Greater work capacity

In a spontaneous change

• The free energy of the system
• decreases (?G lt 0)

• The system becomes more
• stable

• The released free energy can
• be harnessed to do work

• Less free energy (lower G)
• More stable
• Less work capacity

(a) Gravitational motion
(b) Diffusion
(c) Chemical reaction
11
Chemical Reactions and Energy

• Two types
• Endergonic requires energy
• Exergonic releases energy

12
Fig. 8-6a
Reactants
Amount of energy released (?G lt 0)
Energy
Free energy
Products
Progress of the reaction
(a) Exergonic reaction energy released
13
Fig. 8-6b
Products
Amount of energy required (?G gt 0)
Energy
Free energy
Reactants
Progress of the reaction
(b) Endergonic reaction energy required
14
Fig. 8-7
?G lt 0
?G 0
(a) An isolated hydroelectric system
(b) An open hydroelectric system
?G lt 0
?G lt 0
?G lt 0
?G lt 0
(c) A multistep open hydroelectric system
15
Energy Coupling

• Energy coupling using exergonic reactions to
  fuel endergonic reactions
• Exergonic cellular respiration
• Endergonic ATP formation

16
Fig. 8-8
ATP Adenosine Triphosphate
Adenine
Phosphate groups
Ribose
17
Fig. 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O
P

P
P
Energy

i
Inorganic phosphate
Adenosine diphosphate (ADP)
18
Fig. 8-12
ATP

H2O
Energy for cellular work (endergonic, energy-consu
ming processes)
Energy from catabolism (exergonic, energy-releasin
g processes)
ADP
P

i
19
ATP

• Three types of work driven by ATP
• Chemical
• Mechanical
• Transport

20
Fig. 8-10
NH2
NH3
?G 3.4 kcal/mol

Glu
Glu
Glutamic acid
Glutamine
Ammonia
(a) Endergonic reaction
P
ATP phosphorylates glutamic acid, making the
amino acid less stable.
1
ADP


ATP
Glu
Glu
NH2
P
Ammonia displaces the phosphate group, forming
glutamine.
2
NH3
P


i
Glu
Glu
(b) Coupled with ATP hydrolysis, an exergonic
reaction
(c) Overall free-energy change
21
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
ATP
Protein moved
Motor protein
(b) Mechanical work ATP binds noncovalently
to motor proteins, then is hydrolyzed
22
Enzymes

• Lower the activation energy of a reaction (EA)
  and increase the rate of reaction
• Enzymes DO NOT
• Become consumed by the reaction
• Turn into products
• Add energy to the reaction

23
Fig. 8-14
B
A
D
C
Transition state
EA
B
A
C
D
Free energy
Reactants
B
A
?G lt O
D
C
Products
Progress of the reaction
24
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
Products
Progress of the reaction
25
Enzymes

• Enzymes act upon SUBSTRATES
• Every enzyme has a specific 3-D shape and will
  only bind one substrate
• Substrate binds the enzyme at the ACTIVE SITE
• Forms ENZYME-SUBSTRATE COMPLEX
• Upon binding, the active site changes shape
  slightly and grips the substrate even tighter
• Called INDUCED FIT

26
Fig. 8-16
Enzyme-Substrate Complex
Substrate
Active site
Enzyme
Enzyme-substrate complex
(b)
(a)
27
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
6
Active site is available for two
new substrate molecules.
Enzyme
Products are released.
5
4
Substrates are converted to products.
Products
28
How do enzymes lower EA?

• Serve as a template that puts reactants in proper
  orientation
• Stress the bonds of the reactants
• Provide a microenvironment favorable to the
  reaction
• Participate directly in the reaction

29
Fig. 8-18
Optimal temperature for enzyme of thermophilic
(heat-tolerant) bacteria
Optimal temperature for typical human enzyme
Rate of reaction
0
20
40
80
60
100
Temperature (ºC)
(a) Optimal temperature for two enzymes
Optimal pH for pepsin (stomach enzyme)
Optimal pH for trypsin (intestinal enzyme)
Rate of reaction
5
4
3
2
1
0
6
7
8
9
10
pH
(b) Optimal pH for two enzymes
30
Cofactors

• Cofactors non-protein helper of enzymes
• Inorganic cofactors zinc, iron, copper, etc.
• Coenzymes organic cofactors (vitamins, etc)

31
Enzyme Inhibitors

• Two types of enzyme inhibitors
• Competitive binds to the enzyme at the active
  site
• Non-competitive binds to the enzyme somewhere
  other than the active site

32
Fig. 8-19
Substrate
Active site
Competitive inhibitor
Enzyme
Noncompetitive inhibitor
(a) Normal binding
(c) Noncompetitive inhibition
(b) Competitive inhibition
33
Enzyme Regulators

• Allosteric regulation
• Allosteric site where regulator binds to the
  enzyme
• Inhibitor inhibits the enzyme
• Activator activates the enzyme

34
Fig. 8-20a
Active site (one of four)
Allosteric enzyme with four subunits
Regulatory site (one of four)
Activator
Active form
Stabilized active form
Oscillation
Non- functional active site
Inhibitor
Stabilized inactive form
Inactive form
(a) Allosteric activators and inhibitors

35
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
Enzyme 4
Intermediate D
Enzyme 5
End product (isoleucine)