Transcript Chapter 8 (Nov 23-24)

Chapter 8: An Introduction to Metabolism
1.
What is metabolism?
• All of an organisms chemical processes
2. What are the different types of metabolism?
• Catabolism – releases energy by breaking down complex
molecules
• Anabolism – use energy to build up complex molecules
• Catabolic rxns – hydrolysis – break bonds
• Anabolic rxns – dehydration – form bonds
3. How is metabolism regulated?
Enzyme 1
A
Enzyme 3
D
C
B
Reaction 1
Starting
molecule
Enzyme 2
Reaction 2
Reaction 3
Product
Chapter 8: An Introduction to Metabolism
4. What are the different forms of energy?
- Kinetic – energy from molecules in motion
- Potential – energy based on location or structure
- water behind a dam
- bonds in gas/oil
- Chemical energy – bio speak for potential energy
that can be released in a catabolic rxn
Figure 8.2 Transformation between kinetic and potential energy
On the platform, a diver
has more potential energy.
Climbing up converts kinetic
energy of muscle movement
to potential energy.
Diving converts potential
energy to kinetic energy.
In the water, a diver has
less potential energy.
Chapter 8: An Introduction to Metabolism
5. What are the 2 laws of thermodynamics?
- 1st law – Energy is constant. It can be transferred or
transformed but it cannot be created or destroyed.
- 2nd law – Every transfer or transformation of energy increases
the entropy (disorder) of the universe.
Heat
Chemical
energy
(a) First law of thermodynamics: Energy
can be transferred or transformed but
neither created nor destroyed. For
example, the chemical (potential) energy
in food will be converted to the kinetic
energy of the cheetah’s movement in (b).
co2
+
H2O
(b) Second law of thermodynamics: Every energy transfer or transformation increases
the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s
surroundings in the form of heat and the small molecules that are the by-products
of metabolism.
Chapter 8: An Introduction to Metabolism
6.
What is the difference between exergonic & endergonic rxns?
- Exergonic – releases energy
- Endergonic – require energy
- Catabolic rxns – hydrolysis – break bonds – exergonic
- Anabolic rxns – dehydr. syn. – form bonds – endergonic
7. Where does the energy come from to drive rxns in the body?
Adenine
NH
- ATP
2
N
O
–O
P
O–
O
P
O–
O
P
O
N
CH2
N
C
CH
O
O–
H
Phosphate groups
C
HC
O
O
C
H
H Ribose
H
OH
OH
N
Chapter 8: An Introduction to Metabolism
8. How does ATP provide energy?
- hydrolysis of ATP
P
P
P
Adenosine triphosphate (ATP)
H2O
Pi
+
Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
Energy
Figure 8.10 Energy Coupling: Use an exergonic
reaction to fuel an endergonic reaction!!!
Endergonic reaction (dehydration synthesis of NH2 and Glu):
∆G is positive, reaction is not spontaneous
NH2
Glu
+
Glutamic
acid
NH3
Glu
Ammonia
Glutamine
∆G = +3.4 kcal/mol
Exergonic reaction (hydrolysis of ATP): ∆ G is negative, reaction
is spontaneous
ATP
+
H2O
ADP +
Coupled reactions: Overall ∆G is negative;
together, reactions are spontaneous
P
∆G = –7.3 kcal/mol
∆G = –3.9 kcal/mol
Figure 8.11 How ATP drives cellular work
P
i
P
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
Pi
P
Solute
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu + NH3
Reactants: Glutamic acid
and ammonia
NH2
+
P
i
Glu
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
i
Figure 8.12 The ATP cycle
ATP synthesis from
ADP + P i requires energy
(endergonic)
ATP hydrolysis to
ADP + P i yields energy (exergonic)
ATP
Energy from catabolism
(breaking down food molecules
via hydrolysis)
ADP + P
i
Energy for cellular work
(such as dehydration synthesis!)
Chapter 8: An Introduction to Metabolism
9. What is an enzyme?
- biological catalyst made of protein
10. How do enzymes work?
- lower energy of activation (EA)
- EA = energy reactants must absorb before the rxn can start
Figure 8.14 Energy profile of an exergonic reaction
The reactants AB and CD must absorb
enough energy from the surroundings
to reach the unstable transition state,
where bonds can break.
A
B
C
D
Bonds break and new
bonds form, releasing
energy to the
surroundings.
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
∆G < O
C
D
Products
Progress of the reaction
Figure 8.15 The effect of enzymes on reaction rate.
Course of
reaction
without
enzyme
EA
without
enzyme
Free energy
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Chapter 8: An Introduction to Metabolism
11. Some enzyme terms
- substrate – what the enzyme works on – substrate-specific
- active site – where the substrate binds to the enzyme
- induced fit – molecular handshake – when the enzyme
binds to the substrate, it wraps around the substrate
Substrate
Active site
Enzyme- substrate
complex
Enzyme
(a)
(b)
Figure 8.17 The active site and catalytic cycle of an enzyme
How does it work?
• Variety of mechanisms to lower
activation energy & speed up reaction
– Dehydration synthesis
• active site orients substrates in correct position
for reaction/brings substrates closer together
– Hydrolysis
• active site binds substrate & puts stress on
bonds that must be broken, making it easier to
separate molecules
Enzymes in REAL LIFE!
• Enzymes named for reaction they catalyze
– sucrase breaks down sucrose
– proteases break down proteins
– lipases break
down lipids
– DNA polymerase builds DNA
• adds nucleotides
to DNA strand
– pepsin breaks down
proteins (polypeptides)
Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
- temperature
- pH
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria
Rate of reaction
Optimal temperature for
typical human enzyme
0
60
40
20
80
100
Temperature (Cº)
(a) Optimal temperature for two enzymes
Rate of reaction
Optimal pH for pepsin
(stomach enzyme)
0
1
2
3
4 5
pH
Optimal pH
for trypsin
(intestinal
enzyme)
6
OptimalpH
for two
two enzymes
enzymes
(b) Optimal
pH for
7
8
9 10
Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
- temperature
- pH
- cofactors – inorganic non-protein helpers
of enzyme activity (Zn, Fe, Cu)
- coenzymes – organic cofactors (vitamins)
- inhibitors
- competitive – compete w/ substrate for active site
-PENICILLIN – blocks enzyme that bacteria use to
build cell walls
- non-competitive – bind remotely (not to active site, but to secondary site
called ALLOSTERIC SITE,) thus changing enzyme shape & inhibiting activity
-CYANIDE – changes shape of enzyme necessary to make ATP during
cellular respiration
Figure 8.19 Inhibition of enzyme activity
A substrate can
bind normally to the
active site of an
enzyme.
Substrate
Active site
Enzyme
(a) Normal binding
A competitive
inhibitor mimics the
substrate, competing
for the active site.
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.
Competitive
inhibitor
(b) Competitive inhibition
Noncompetitive inhibitor
(c) Noncompetitive inhibition
Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
Allosteric activater
13. How are enzymes regulated?
stabilizes active from
Allosteric enyzme
Active site
with four subunits
(one of four)
- allosteric inhibitors
-keeps enzyme inactive
Regulatory
- allosteric activators
site (one
Activator
-keeps enzyme active of four)
Active form
Stabilized active form
Oscillation
Allosteric inhibiter
stabilizes inactive form
NonInactive form Inhibitor
functional
active
site
Stabilized inactive
form
Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
13. How are enzymes regulated?
- allosteric inhibitors
- allosteric activators
Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
13. How are enzymes regulated?
- allosteric inhibitors
- allosteric activators
Active site
available
-final product is inhibitor
of earlier step!
-prevents unnecessary
accumulation of product
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
- feedback inhibition
Initial substrate
(threonine)
Intermediate A
Feedback
inhibition
Active site of
enzyme 1 no
longer binds
threonine;
pathway is
switched off
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Isoleucine
binds to
allosteric
site
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)