Transcript An Introduction to Metabolism

An Introduction to Metabolism
A.P. Biology
The living cell
Is a miniature factory where thousands of
reactions occur
– Converts energy in many ways
Bioluminescence
Figure 8.1
Metabolism
– Is the totality of an organism’s chemical
reactions
– Arises from interactions between molecules
– An organism’s metabolism transforms matter and
energy, subject to the laws of thermodynamics
Thermodynamics
– Is the study of energy transformations
• The first law of thermodynamics
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
• The second law of thermodynamics
– Spontaneous changes that do not require outside energy
increase the entropy, or disorder, of the universe
st
1
Law of Thermodynamics
Chemical
energy
(a)
Figure 8.3
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).
nd
2
Law of Thermodynamics
Heat
co2
+
H2O
(b)
Figure 8.3
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.
Living systems
– Increase the entropy
of the universe
– Use energy to
maintain order
Metabolic Pathways
•A metabolic pathway has many steps
–That begin with a specific molecule and end with
a product
–That are each catalyzed by a specific enzyme
Enzyme 1
A
Enzyme 3
D
C
B
Reaction 1
Starting
molecule
Enzyme 2
Reaction 2
Reaction 3
Product
Types of Metabolic Pathways
• Catabolic pathways
– Break down complex molecules into simpler
compounds
– Release energy
• Anabolic pathways
– Build complicated molecules from simpler ones
– Consume energy
Energy can be converted
from one form to another
On the platform, a diver
has more potential energy.
Climbing up converts kinetic
energy of muscle movement
Figure 8.2
to potential energy.
Diving converts potential
energy to kinetic energy.
In the water, a diver has
less potential energy.
Free Energy
• Free energy measures the portion of a system’s energy that
can perform work when the temperature & pressure are
uniform throughout the system. (like in cells)
• The free-energy change of a reaction tells us whether the
reaction occurs spontaneously
• A living system’s free energy
– Is energy that can do work under cellular conditions
Change in free energy, ∆G
• The change in free energy, ∆G during
a biological process
– Is related directly to the enthalpy
change (∆H) and the change in entropy
∆G = ∆H – T∆S
T = Absolute temp in Kelvin (K)
∆G
• The value of ∆ G for a reaction at any moment in
time tells us two things.
• The sign of ∆ G tells us in what direction the
reaction has to shift to reach equilibrium.
• The magnitude of ∆ G tells us how far the
reaction is from equilibrium at that moment.
At maximum stability
–The system is at equilibrium
• More free energy (higher G)
• Less stable
• Greater 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
.
• Less free energy (lower G)
• More stable
• Less work capacity
(a)
Figure 8.5
Gravitational motion. Objects (b) Diffusion. Molecules
(c) Chemical reaction. In a
move spontaneously from a
cell, a sugar molecule is
in a drop of dye diffuse
until they are randomly
higher altitude to a lower one.
broken down into simpler
dispersed.
molecules.
Free Energy
• During a spontaneous change
– Free energy decreases and the stability of a
system increases
 For a spontaneous reaction to occur:
– Loss of enthalpy (Heat)
-or– Loss of order (Gain in entropy)
-or both
Exergonic and Endergonic
Reactions in Metabolism
• An exergonic reaction
– Proceeds with a net release of free energy and
is spontaneous
Free energy
Reactants
Amount of
energy
released
(∆G <0)
Energy
Products
Progress of the reaction
Figure 8.6
(a) Exergonic reaction: energy released
Endergonic reaction
–Is one that absorbs free energy from its surroundings
and is non-spontaneous
Free energy
Products
Energy
Reactants
Progress of the reaction
Figure 8.6
(b) Endergonic reaction: energy required
Amount of
energy
released
(∆G>0)
Reactions in a closed system
– Eventually reach equilibrium
∆G < 0
Figure 8.7 A
∆G = 0
(a) A closed hydroelectric system. Water flowing downhill turns a turbine
that drives a generator providing electricity to a light bulb, but only until
the system reaches equilibrium.
Reactions in an open system
• Cells in our body
– Experience a constant flow of materials
in and out, preventing metabolic
pathways from reaching equilibrium
(b) An open hydroelectric
system. Flowing water
keeps driving the generator
because intake and outflow
of water keep the system
from reaching equilibrium.
Figure 8.7
∆G < 0
An analogy for cellular
respiration
∆G < 0
∆G < 0
∆G < 0
Figure 8.7
(c) A multi-step open hydroelectric system. Cellular respiration is
analogous to this system: Glucose is broken down in a series
of exergonic reactions that power the work of the cell. The product
of each reaction becomes the reactant for the next, so no reaction
reaches equilibrium.
ATP – Adenosine Tri-phosphate
• ATP powers cellular work by coupling
exergonic reactions to endergonic
reactions
• A cell does three main kinds of work
– Mechanical
– Transport
– Chemical
The Structure and
Hydrolysis of ATP
– Provides energy for cellular functions
Adenine
N
O
O
-O
O
-
O
-
Phosphate groups
Figure 8.8
O
O
C
C
N
HC
O
O
O
NH2
N
CH2
-
O
H
N
H
H
H
OH
CH
C
OH
Ribose
Energy is released from ATP
When the terminal phosphate bond is broken
and the negative charge on the PO4 groups repel
P
P
P
Adenosine triphosphate (ATP)
H2O
P
i
+
Figure 8.9 Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
Energy
ATP hydrolysis
can be coupled to other reactions
Endergonic reaction: ∆G is positive, reaction
is not spontaneous
NH2
Glu
+
Glutamic
acid
ATP hydrolysis
Glu
Ammonia
Glutamine
∆G = +3.4 kcal/mol
Exergonic reaction: ∆ G is negative, reaction
is spontaneous
ATP
Figure 8.10
NH3
+
H2O
ADP +
P
∆G = - 7.3 kcal/mol
Coupled reactions: Overall ∆G is negative;
∆G = –3.9 kcal/mol
together, reactions are spontaneous
ATP drives endergonic reactions
By phosphorylation, transferring a
phosphate to other molecules
Three types of
cellular work
are powered by
the hydrolysis
of ATP
P
i
P
Motor protein
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
ATP
P
P
P
i
Solute
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
P
Glu + NH3
Reactants: Glutamic acid
and ammonia
Figure 8.11
NH2
Glu
+
P
i
Product (glutamine)
made
(c) Chemical work: ATP phosphorylates key reactants
i
The Regeneration of ATP
• Catabolic pathways
– Drive the regeneration of ATP from ADP and
phosphate
ATP hydrolysis to
ADP + P i yields energy
ATP synthesis from
ADP + P i requires energy
ATP
Energy from catabolism
(exergonic, energy yielding
processes)
Figure 8.12
Energy for cellular work
(endergonic, energyconsuming processes)
ADP + P
i
∆ G = +7.3
kcal/mol
∆ G = -7.3
kcal/mol
Enzymes
• Enzymes speed up metabolic reactions by
lowering energy barriers
• A catalyst
– Is a chemical agent that speeds up a reaction without
being consumed by the reaction
• An enzyme
– Is a catalytic protein
E + S  ES  E + P
Every chemical reaction between
molecules
Involves both bond breaking and
bond forming
•Hydrolysis is an example of a chemical reaction
CH2OH
CH2OH
O
O
H H
H
H
OH
H HO
O
+
CH2OH
H
OH H
OH
Sucrase
H2O
CH2OH
O H
H
H
OH H
OH
HO
H
OH
CH2OH
O
HO
H HO
H
CH2OH
OH H
Sucrose
Glucose
Fructose
C12H22O11
C6H12O6
C6H12O6
Figure 8.13
Activation Energy (EA)
• The activation energy, EA
– Is the initial amount of energy needed to
start a chemical reaction
– Is often supplied in the form of heat
from the surroundings in a system
• An enzyme catalyzes reactions
– By lowering the EA barrier
Exergonic Reactions
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
C
D
∆G < O
Products
Progress of the reaction
Figure 8.14
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Free energy
Reactants
∆G is unaffected
by enzyme
Course of
reaction
with enzyme
Products
Progress of the reaction
Figure 8.15
Substrate Specificity of Enzymes
Substrate
• The substrate
– Is the reactant an enzyme acts on
Active site
• The enzyme
– Binds to its substrate, forming an
enzyme-substrate complex
Enzyme
• The active site
Figure 8.16
– Is the region on the enzyme where
the substrate binds
(a)
Induced fit of a substrate
– Brings chemical groups of the active site
into positions that enhance their ability to
catalyze the chemical reaction
Enzyme- substrate
complex
Figure 8.16
(b)
Enzyme & Substrate fit like
a lock & key (Shape specific)
pH or temperature can
change the active site
shape on any enzyme
Active site is where the
reactants bind to the enzyme
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Enzyme-substrate
complex
6 Active site
Is available for
two new substrate
Mole.
Enzyme
5 Products are
Released.
Figure 8.17
Products
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.
The active site can lower an
EA barrier by:
–
–
–
–
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Covalently bonding to the substrate
The activity of an enzyme
– Is affected by general environmental factors
– Temperature
– pH
Optimal temperature for
typical human enzyme
Optimal temperature for
enzyme of thermophilic
Rate of reaction
(heat-tolerant)
bacteria
0
20
40
Temperature (Cº)
(a) Optimal temperature for two enzymes
Figure 8.18
80
100
Optimal pH for pepsin
(stomach enzyme)
Rate of reaction
Optimal pH
for trypsin
(intestinal
enzyme)
3
4
0
2
1
(b) Optimal pH for two enzymes
Figure 8.18
5
6
7
8
9
Enzyme cofactors
• Cofactors
– Are non-protein enzyme helpers e.g. zinc,
iron, copper atoms
• Coenzymes
– Are organic cofactors e.g. vitamins
coenzyme
abbreviation
entity transfered
nicotine
adenine
dinucelotide
NAD - partly
composed of
niacin
electron
(hydrogen atom)
nicotine
adenine
dinucelotide
phosphate
NADP -Partly
composed of
niacin
electron
(hydrogen atom)
flavine
adenine
dinucelotide
FAD - Partly
composed of
riboflavin (vit.
B2)
electron
(hydrogen atom)
coenzyme A
CoA
Acyl groups
coenzymeQ
CoQ
electrons
(hydrogen atom)
coenzymes in group transfer
reactions
Enzyme Inhibition
Enzyme Inhibitors
• Competitive
inhibitors
– Bind to the active
site of an enzyme,
competing with the
substrate
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.
Figure 8.19
(b) Competitive inhibition
Competitive
inhibitor
Enzyme Inhibitors
• Noncompetitive inhibitors
– Bind to another part of an enzyme, changing
the function
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
Figure 8.19
(c) Noncompetitive inhibition
Enzyme Regulation
• Regulation of enzyme activity helps control
metabolism
• A cell’s metabolic pathways
– Must be tightly regulated
Allosteric regulation
– Is the term used to describe any case in which
a protein’s function at one site is affected by
binding of a regulatory molecule at another
Activator
Inhibitor
Allosteric enyzme
with four subunits
Regulatory
site (one
of four)
Active site
(one of four)
Activator
Active form
Stabilized active form
Oscillation
Allosteric activater
stabilizes active form
NonInactive form Inhibitor
functional
active
site
Figure 8.20
Allosteric activater
stabilizes active from
Stabilized inactive
form
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors
dissociate when at low concentrations. The enzyme can then oscillate again.
Cooperativity
– Is a form of allosteric regulation that
can amplify enzyme activity
Binding of one substrate molecule to
active site of one subunit locks
all subunits in active conformation.
Substrate
Inactive form
Figure 8.20
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.
Feedback inhibition
Active site
available
– The end product
of a metabolic
pathway shuts
down the pathway
Initial substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Isoleucine
used up by
cell
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
Figure 8.21
End product
(isoleucine)
How to Name Enzymes
• Change the ending on the name of the
substrate to –ase
• Sucrose (substrate) – Sucrase (enzyme)
• Lipid – Lipase
• Protein – Protease
• DNA - DNAse