Transcript Introduction to Metabolism

Introduction to Metabolism
AP MinKnow
•The key role of ATP in energy coupling.
•That enzymes work by lowing the energy of
activation.
•The catalytic cycle of an enzyme that results in the
production of a final product.
•The factors that influence the efficiency of enzymes.
Energy can’t be created or
destroyed, but it can be
transferred!!!
Concept 8.1: An organism’s metabolism
transforms matter and energy, subject to the
laws of thermodynamics
• Metabolism is the totality of an organism’s chemical
reactions
– An emergent property of life
• A metabolic pathway begins with a specific molecule
and ends with a product
– Each step is catalyzed by a specific enzyme
Enzyme 1
Enzyme 2
B
A
Reaction 1
Enzyme 3
C
Reaction 2
D
Reaction 3
Product
Bioenergetics - is the study of how organisms
manage their energy resources
• Catabolic pathways
release energy by
breaking down
complex molecules
into simpler
compounds
• Anabolic pathways
consume energy to
build complex
molecules from
simpler ones
Energy is the capacity to do work
• Kinetic energy is energy associated with motion
• Heat (thermal energy) is kinetic energy associated
with random movement of atoms or molecules
• Potential energy is energy that matter possesses
because of its location or structure
• Chemical energy is potential energy available for
release in a chemical reaction
• Energy can be converted from one form to another
Animation: Energy Concepts
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Enzyme 1
A
Reaction 1
Starting
molecule
Enzyme 2
B
Enzyme 3
C
Reaction 2
D
Reaction 3
Product
The Laws of Energy Transformation
• Thermodynamics is the
study of energy
transformations
– A closed system, such as
that approximated by liquid
in a thermos, is isolated from
its surroundings
– In an open system, energy
and matter can be
transferred between the
system and its surroundings
• Organisms are open
systems
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The Laws of Thermodynamics
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We care about the 1st and 2nd laws of thermodynamics!
• 1st Law of
Thermodynamics
• The 1st Law of
Thermodyamics simply
states that energy can be
neither created nor
destroyed (conservation of
energy).
–
Thus power generation
processes and energy
sources actually involve
conversion of energy
from one form to
another, rather than
creation of energy from
nothing. For example:
Automobile Engine
Chemical  Kinetic
Heater/Furnace
Chemical  Heat
Hydroelectric
Gravitational 
Electrical
Solar
Optical  Electrical
Nuclear
Nuclear  Heat,
Kinetic, Optical
Battery
Chemical  Electrical
Food
Chemical  Heat,
Kinetic
Photosynthesis
Optical  Chemical
2nd Law of Thermodynamics (Entropy)
1. Heat flows
spontaneously
from a hot body
to a cool one.
2. One cannot
convert heat
completely into
useful work.
3. Everything moves
towards disorder.
(increasing
entropy)
Biological Order and Disorder
1. The evolution of
more complex
organisms does not
violate the second
law of
thermodynamics
2. Entropy (disorder)
may decrease in an
organism, but the
universe’s total
entropy increases
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Fig. 8-3
We really care about 1st and 2nd Laws!!
Heat
Chemical
energy
(a) First law of thermodynamics
CO2
+
H2O
(b) Second law of thermodynamics
∆G = ∆H – T∆S
• ∆G – free energy in the system (J/mol)
–
∆G < 0, spontaneous
–
∆G > 0, non-spontaneous
• ∆H - is the amount of heat released or absorbed when a
chemical reaction occurs at constant pressure. (J/mol)
• T – Thermal Energy (K)
• ∆S – Entropy is the measure of disorder (J/K*mol)
Fig. 8-5a
• More free energy (higher G)
• Less stable
• Greater work capacity
In a spontaneous 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
• Less free energy (lower G)
• More stable
• Less work capacity
∆G = ∆H – T∆S
Burning glucose (sugar): an exergonic reaction
high
high
activation energy needed
to ignite glucose
energy
content
of
molecules
glucose + O2
energy released
by burning glucose
glucose
energy
content
of
molecules
progress of reaction
net energy
captured by
synthesizing
glucose
CO2 + H2O
CO2 + H2O
low
activation
energy from
light captured
by photosynthesis
low
progress of reaction
Photosynthesis: an endergonic reaction
• More free energy (higher G)
• Less stable
• Greater work capacity
In a spontaneous 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
• Less free energy (lower G)
• More stable
• Less work capacity
(a) Gravitational motion
(b) Diffusion
(c) Chemical reaction
Exergonic and Endergonic
Reactions in Metabolism
• An endergonic
reaction absorbs
free energy from
its surroundings
and is
nonspontaneous
Free energy
Amount of
energy
released
(∆G < 0)
Energy
Products
Progress of the reaction
(a) Exergonic reaction: energy released
Products
Free energy
• An exergonic
reaction
proceeds with a
net release of
free energy and is
spontaneous
Reactants
Amount of
energy
required
(∆G > 0)
Energy
Reactants
Progress of the reaction
(b) Endergonic reaction: energy required
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Fig. 8-7
∆G < 0
∆G = 0
(a) An isolated hydroelectric system
(b) An open hydroelectric
system
∆G < 0
∆G < 0
∆G < 0
∆G < 0
(c) A multistep open hydroelectric system
∆G < 0
∆G < 0
∆G < 0
(c) A multistep open hydroelectric system
Enzyme 1
A
Reaction 1
Starting
molecule
Enzyme 2
B
Enzyme 3
C
Reaction 2
D
Reaction 3
Product
• How does the second law of thermodynamics help
explain the diffusion of a substance across a
membrane?
• Cellular respiration uses glucose and oxygen, which
have high levels of free energy, and releases carbon
dioxide and water, which have low levels of free
energy. Is respiration spontaneous or not? Is it
exergonic or endergonic? What happens to the
energy released from glucose?
• A key process in metabolism is the transport of
hydrogen ions across a membrane to create a
concentration gradient. Other processes can result in
an equal concentration of hydrogen ions on each side.
Which arrangement of hydrogen ions allows them to
perform work in this system?
The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s
energy shuttle
Adenine
Phosphate groups
Ribose
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Fig. 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O
Pi
+
Inorganic phosphate
P
P
+
Adenosine diphosphate (ADP)
Energy
Concept 8.3: ATP powers cellular work by
coupling exergonic reactions to endergonic
reactions
• A cell does three main kinds of work:
– Chemical
– Transport
– Mechanical
• To do work, cells manage energy resources by
energy coupling, the use of an exergonic process
to drive an endergonic one
• Most energy coupling in cells is mediated by ATP
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Fig. 8-11
Membrane protein
P
Solute
Pi
Solute transported
(a) Transport work: ATP phosphorylates
transport proteins
ADP
+
ATP
Pi
Vesicle
Cytoskeletal track
ATP
Motor protein
Protein moved
(b) Mechanical work: ATP binds noncovalently
to motor proteins, then is hydrolyzed
Fig. 8-10
NH2
Glu
Glutamic
acid
NH3
+
∆G = +3.4 kcal/mol
Glu
Ammonia
Glutamine
(a) Endergonic reaction
1 ATP phosphorylates
glutamic acid,
making the amino
acid less stable.
P
+
Glu
ATP
Glu
+ ADP
NH2
2 Ammonia displaces
the phosphate group,
forming glutamine.
P
Glu
+
NH3
Glu
+ Pi
(b) Coupled with ATP hydrolysis, an exergonic reaction
(c) Overall free-energy change
Fig. 8-12
ATP + H2O
Energy from
catabolism (exergonic,
energy-releasing
processes)
ADP + P i
Energy for cellular
work (endergonic,
energy-consuming
processes)
Catalysts, Enzymes, and Reactions
• A catalyst is a
chemical agent that
speeds up a reaction
without being
consumed by the
reaction
• An enzyme is a
catalytic protein
Sucrose (C12H22O11)
Sucrase
– Hydrolysis of sucrose
by the enzyme
sucrase is an
example of an
enzyme-catalyzed Glucose (C H O )
6 12 6
reaction
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Fructose (C6H12O6)
Fig. 8-14
A
B
C
D
Transition state
A
B
C
D
EA
Reactants
A
B
∆G < O
C
D
Products
Progress of the reaction
How Enzymes Lower the EA Barrier
Fig. 8-15
• Enzymes
catalyze
reactions by
lowering the
EA barrier
• Enzymes do
not affect the
change in
free energy
(∆G); instead,
they hasten
reactions that
would occur
eventually
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Animation: How Enzymes Work
Substrate Specificity of Enzymes
• substrate - The reactant
that an enzyme acts on
• enzyme-substrate
complex - The enzyme
binds to its substrate,
forming an enzymesubstrate complex
• active site - is the region
on the enzyme where the
substrate binds
• Induced fit of a substrate
brings chemical groups of
the active site into
positions that enhance
their ability to catalyze the
reaction
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Fig. 8-16
Substrate
Active site
Enzyme
(a)
Enzyme-substrate
complex
(b)
Catalysis in the Enzyme’s Active Site
How do Enzymes Work?
• In an enzymatic reaction, the substrate binds to
the active site of the enzyme
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
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Fig. 8-17
1 Substrates enter active site; enzyme
changes shape such that its active site
enfolds the substrates (induced fit).
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
Substrates
Enzyme-substrate
complex
6 Active
site is
available
for two new
substrate
molecules.
Enzyme
5 Products are
released.
4 Substrates are
converted to
products.
Products
3 Active site can lower EA
and speed up a reaction.
–
–
General
environmental
factors, such as
temperature
and pH
Chemicals that
specifically
influence the
enzyme
(cofactor)
• Coenzyme
Optimal temperature for
enzyme of thermophilic
(heat-tolerant)
bacteria
40
60
80
Temperature (ºC)
(a) Optimal temperature for two enzymes
0
20
Optimal pH for pepsin
(stomach enzyme)
100
Optimal pH
for trypsin
(intestinal
enzyme)
Rate of reaction
• An enzyme’s
activity can be
affected by
Rate of reaction
Optimal temperature for
typical human enzyme
4
5
pH
(b) Optimal pH for two enzymes
0
1
2
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3
6
7
8
9
10
Enzyme Inhibitors
• Competitive inhibitors bind to the active site
of an enzyme, competing with the substrate
• Noncompetitive inhibitors bind to another
part of an enzyme, causing the enzyme to
change shape and making the active site less
effective
• Examples of inhibitors include toxins, poisons,
pesticides, and antibiotics
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Fig. 8-19
Substrate
Active site
Competitive
inhibitor
Enzyme
Noncompetitive inhibitor
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive inhibition
Enzyme Inhibitors
• Competitive inhibitors bind to the active site
of an enzyme, competing with the substrate
• Noncompetitive inhibitors (Allosteric
inhibitors)bind to another part of an enzyme,
causing the enzyme to change shape and
making the active site less effective
• Examples of inhibitors include toxins, poisons,
pesticides, and antibiotics
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Allosteric Regulation
of Enzymes
• Allosteric regulation
may either inhibit or
stimulate an enzyme’s
activity
• Allosteric regulation
occurs when a
regulatory molecule
binds to a protein at
one site and affects
the protein’s function
at another site
Allosteric enzyme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Activator
Active form
Stabilized active form
Oscillation
NonInhibitor
functional Inactive form
active
site
(a) Allosteric activators and inhibitors
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Stabilized inactive
form
Identification of Allosteric Regulators (Your
Drugs!!!)
• Allosteric regulators are attractive drug
candidates for enzyme regulation
• Inhibition of proteolytic enzymes called
caspases may help management of
inappropriate inflammatory responses
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Fig. 8-21
EXPERIMENT
Caspase 1
Active
site
Substrate
SH
Known active form
SH
Active form can
bind substrate
SH Allosteric
binding site
Allosteric
Known inactive form inhibitor
S–S
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form
RESULTS
Caspase 1
Active form
Inhibitor
Allosterically
Inactive form
inhibited form
Fig. 8-21b
RESULTS
Caspase 1
Active form
Inhibitor
Allosterically
Inactive form
inhibited form
Feedback Inhibition
Fig. 8-22
• In feedback
inhibition, the end
product of a
metabolic pathway
shuts down the
pathway
• Feedback
inhibition prevents
a cell from wasting
chemical
resources by
synthesizing more
product than is
needed
Initial substrate
(threonine)
Active site
available
Isoleucine
used up by
cell
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Feedback
inhibition
Isoleucine
binds to
allosteric
site
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Enzyme 2
Active site of
enzyme 1 no
longer binds Intermediate B
threonine;
pathway is
Enzyme 3
switched off.
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)