Intro to Metabolism
Campbell Chapter 8
http://www.youtube.com/watch?v=Xy0UBpagsu8
http://ag.ansc.purdue.edu/sheep/ansc442/Semprojs/2003/spiderlamb/eatsheep.gif
http://www.gifs.net
• Metabolism is the sum of an organism’s chemical
reactions
• Metabolism is an emergent property of life that
arises from interactions between molecules
within the cell
http://www.encognitive.com/images/metabolic-pathways.png
Bond Energies and the Big Picture
• 1.
http://www.angelfire.com/ak2/chemists/project5.
html(photosynthesis/cell respiration cycle)
• 2.
http://users.rcn.com/jkimball.ma.ultranet/Biolog
yPages/B/BondEnergy.html#Gibbs
• (bond energies and Delta G. follow link to
electronegativity and bond energy table)
• 3.
http://www.saskschools.ca/curr_content/che
m30_05/1_energy/energy3_3.htm
A metabolic pathway begins with a specific
molecule and ends with a product
• Each step is catalyzed by a specific enzyme
BIOCHEMICAL PATHWAY
VIDEO
ENZYMES THAT WORK TOGETHER IN A PATHWAY CAN BE
Concentrated in
specific location
Covalently
bound in
complex
Soluble with
free floating
intermediates
Biochemistry Lehninger
Attached to
a membrane
in sequence
CATABOLIC PATHWAY (CATABOLISM)
Release of energy by the breakdown of
complex molecules to simpler compounds
EX: digestive enzymes break down food
ANABOLIC PATHWAY (ANABOLISM)
consumes energy to build complicated
molecules from simpler ones
EX: linking amino acids to form proteins
http://www.sciencelearn.org.nz/var/sciencelearn/storage/images/contexts/nanoscience/sci_media/images/chemical_reactions_involve_making_new_combination
s/53823-2-eng-NZ/chemical_reactions_involve_making_new_combinations_full_size_landscape.jpg
Krebs Cycle connects the catabolic and anabolic pathways
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/I/IntermediaryMetabolism.html
Forms of Energy
• ENERGY = capacity to cause change
• Energy exists in various forms
(some of which can perform work)
• Energy can be converted from one form to
another
KINETIC ENERGY –
energy associated with motion
– HEAT (thermal energy) is kinetic energy
associated with random movement of
atoms or molecules
POTENTIAL ENERGY = energy that matter
possesses because of its location or
structure
– CHEMICAL energy is potential energy
available for release in a chemical
reaction
On the platform, the 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, the diver has
less potential energy.
THERMODYNAMICS
= the study of energy transformations
• CLOSED system (EX: liquid in a thermos)
= isolated from its surroundings
• OPEN system
energy + matter can be transferred between
the system and its surroundings
• Organisms are open systems
http://ag.ansc.purdue.edu/sheep/ansc442/Semprojs/2003/spiderlamb/eatsheep.gif
The First Law of Thermodynamics
= energy of the universe is constant
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
• The first law is also called the principle of
CONSERVATION OF ENERGY
http://www.pxleyes.com/photoshop-picture/4a3b747566555/remote-control.html
http://www.suncowboy.com/solar101.php
The Second Law of Thermodynamics
During every energy transfer or transformation
•entropy (disorder) of the universe INCREASES
•some energy is unusable, often lost as heat
http://hyperphysics.phy-astr.gsu.edu/hbase/therm/entrop.html
http://www.janebluestein.com/articles/whatswrong.html
First law of thermodynamics
Chemical
energy
Second law of thermodynamics
Heat
CO2
H2O
ORGANISMS are energy TRANSFORMERS!
Spontaneous processes occur without energy input;
they can happen quickly or slowly
For a process to occur without energy input, it must
increase the entropy of the universe
Free-Energy Change (G) can help tell
which reactions will happen
∆G = change in free energy
∆H = change in total energy (enthalpy) or change
∆S = entropy (amount of “disorder”)
T = temperature
∆G = ∆H - T∆S
•Only processes with a negative ∆G are
spontaneous
•Spontaneous processes can be harnessed to
perform work
http://2ndlaw.oxy.edu/gibbs.html (link to discussion for the advanced biology/physics student)
Exergonic and Endergonic Reactions in Metabolism
• EXERGONIC reactions
(- ∆G)
• Release energy
• are spontaneous
ENDERGONIC reactions
(+ ∆G)
• Absorb energy from
their surroundings
• are non-spontaneous
Concept 8.3: ATP powers cellular work by coupling
exergonic reactions to endergonic reactions
• A cell does three main kinds of work:
– Mechanical
– Transport
– Chemical
• In the cell, the energy from the exergonic
reaction of ATP hydrolysis can be used to drive
an endergonic reaction
• Overall, the coupled reactions are exergonic
ATP (adenosine triphosphate) is the cell’s renewable and
reusable energy shuttle
ATP provides energy for cellular functions
Energy to charge ATP comes from catabolic reactions
Adenine
Phosphate groups
Ribose
LE 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O
Pi
+
Inorganic phosphate
P
P
Adenosine diphosphate (ADP)
+
Energy
ATP
Energy for cellular work
provided by the loss of
phosphate from ATP
Energy from catabolism
(used to charge up
ADP into ATP
ADP +
P
i
Endergonic reaction:
DG is positive, reaction is not spontaneous
NH2
Glu
+
NH3
Ammonia
Glutamic
acid
G = +3.4 kcal/mol
Glu
Glutamine
Exergonic reaction:
DG is negative, reaction is spontaneous
ATP
+
H2O
Coupled reactions:
Overall DG is negative;
Together, reactions are spontaneous
ADP +
Pi
G = –7.3 kcal/mol
G = –3.9 kcal/mol
Coupled Reactions: Minimize energy loss
•
The proximity of molecules (enzymes, reactants) in biochemical
pathways allow the maximum harnessing of the motion created by
electronic binding rearrangements (aka “bond formation/creation) so
the the amount of energy lost as heat is reduced.
•
Maximum capture of translational energy and less entropy gain;
maximizing the amount of USEFUL WORK THAT CAN BE DONE.
•
Picture gears in an engine in proximity, as one gear turns, another
turns; although heat is always lost, the proximity of the gears is critical
for the operation of the system. The same is true for biochemical
pathways; only the gears are molecules.
•
Coupled Reaction Animation:
http://www.indiana.edu/~oso/animations/useATP.html
–
1st the enzyme provides a surface to bring reactants into proximity.
–
2nd, the translational (kinetic energy) transfer is captured as one
molecule experiences a bond rearrangement a.k.a “electronic binding
reconfiguration.
Coupled Reaction Videos
•
http://www.youtube.com/watch?v=VxuQ71l5rEw&feature=results_video&
playnext=1&list=PL496A22971EDE9E61
•
(ATP Synthesis animation; coupled reaction)
•
http://www.youtube.com/watch?v=5sGqbnQoyrI&feature=results_video&playne
xt=1&list=PL496A22971EDE9E61
•
ATP Synthase animation #2
•
http://www.youtube.com/watch?v=VxuQ71l5rEw&feature=results_video&playn
ext=1&list=PL496A22971EDE9E61
•
(lecture video)
LE 8-11
Pi
P
Motor protein
Protein moved
Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
+
Pi
ATP
Pi
P
Solute transported
Solute
Transport work: ATP phosphorylates transport proteins
P
Glu
NH2
+
NH3
Reactants: Glutamic acid
and ammonia
+
Glu
Pi
Product (glutamine)
made
Chemical work: ATP phosphorylates key reactants
Every chemical reaction between molecules involves
bond breaking and bond forming
ACTIVATION ENERGY =
amount of energy required to get chemical reaction started
Activation energy is often supplied in the form
of heat from the surroundings
Free energy animation
IT’S LIKE PUSHING A
SNOWBALL UP A HILL . . .
Once you get it up there,
it can roll down by itself
http://www.chuckwagondiner.com/art/matches.jpg
http://plato.acadiau.ca/COURSES/comm/g5/Fire_Animation.gif
The Activation Energy Barrier
LE 8-14
A
B
C
D
Free energy
Transition state
A
B
C
D
EA
Reactants
A
B
G < O
C
D
Products
Progress of the reaction
http://www.learnerstv.com/animation/animation.php?ani=161&cat=Biology (animation)
CATALYST = a chemical agent that speeds up a
reaction without being consumed by the
reaction
ENZYMES = biological catalysts
Most enzymes are PROTEINS
Exception = ribozymes (RNA) Ch 17 & 26
Enzyme Activity Animations
•
The red ball in the animation represents a reactant that exhibits kinetic motion
in response the its surroundings.
•
At cell temperatures, the motion (kinetic, translational or “collision” energy) is
often not enough to allow a reaction to occur.
•
The enzyme (protein with specific “charged or uncharged amino acids) provide
a surface the forces the proximity of the reactants.
•
The enzyme thereby reduces the amount of kinetic energy required to initiate a
reaction (REDUCED Ea).
•
http://www.indiana.edu/~oso/animations/SN2%2BE.html (animation)
•
NOTE: enzymes cannot perform a reaction that is thermodynamically
impossible. Only the RATE of the reaction is changed.
•
In mitochondria...the electron transport chain comprises an enzymatic series of electron donors and acceptors. Each
electron donor passes electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a
process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron
acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton
gradient across the mitochondrial membrane by actively “pumping” protons into the intermembrane space, producing a
thermodynamic state that has the potential to do work. The entire process is called oxidative phosphorylation, since ADP is
phosphorylated to ATP using the energy of hydrogen oxidation in many steps.
Free energy
Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Reactants
Course of
reaction
with enzyme
G is unaffected
by enzyme
Products
Progress of the reaction
ENZYMES LOWER ACTIVATION ENERGY
BY:
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
Enzymes change
ACTIVATION ENERGY
but NOT energy of
REACTANTS or PRODUCTS
http://www.learnerstv.com/animation/animation.php?ani=161&cat=Biology
http://sarahssureshots.wikispaces.com/Focus+on+Proteins
http://www.ac-montpellier.fr/sections/personnelsen/ressources-pedagogiques/education-artistique/consultation-avis-du
ENZYMES
•
•
•
•
•
•
Most are proteins
Lower activation energy
Specific
Shape determines function
Reusuable
Unchanged by reaction
Image from: http://www.hillstrath.on.ca/moffatt/bio3a/digestive/enzanim.htm
• The REACTANT that an enzyme acts on
= SUBSTRATE
• Enzyme + substrate =
ENZYME-SUBSTRATE COMPLEX
• Region on the enzyme where the substrate
binds = ACTIVE SITE
• Substrate held in active site by WEAK
interactions (ie. hydrogen and ionic bonds)
TWO MODELS PROPOSED
• LOCK & KEY
Active site on enzyme
fits substrate exactly
• INDUCED FIT
Binding of substrate causes change
in active site so it fits substrate
more closely
http://www.grand-illusions.com/images/articles/toyshop/trick_lock/mainimage.jpg
http://commons.wikimedia.org/wiki/File:Induced_fit_diagram.png
Enzyme Activity can be affected by:
– General environmental factors, such as
temperature, pH, salt concentration, etc.
– Chemicals that specifically influence the
enzyme
See a movie
Choose narrated
http://www.desktopfotos.de/Downloads/melt_cd.jpg
http://www.nealbrownstudio.com/adm/photo/163_nb_fried_egg.jpg
TEMPERATURE & ENZYME ACTIVITY
Each enzyme has an optimal temperature at which it
can function (Usually near body temp)
http://www.animated-gifs.eu/meteo-thermometers/001.htm
http://www.uic.edu/classes/bios/bios100/lectures/chemistry.htm
Increasing temperature increases the rate of an
enzyme-catalyzed reaction up to a point.
Above a certain temperature, activity begins to
decline because the enzyme begins to denature.
pH and ENZYME ACTIVITY
Each enzyme has an optimal pH at which it can
function
http://www.wissensdrang.com/media/wis9r.gif
COFACTORS
= non-protein enzyme helpers
•
EX: Zinc, iron, copper
COENZYMES
= organic enzyme helpers
• Ex: vitamins
http://www.elmhurst.edu/~chm/vchembook/595FADcoq.html
Enzyme Kinetics: Studies RATES of reactions;usually
measures ∆substrate concentration over ∆ Time
← V MAX
Adding substrate increases activity up to a point
REGULATION OF ENZYME PATHWAYS
• GENE REGULATION
cell switches on or off the genes that code for
specific enzymes
REGULATION OF ENZYME PATHWAYS
• FEEDBACK INHIBITION
end product of a pathway interacts with and
“turns off” an enzyme earlier in pathway
FEEDBACK INHIBITION
• prevents a cell from wasting chemical resources
by synthesizing more product than is needed
NEGATIVE FEEDBACK
– An accumulation of an end product slows
the process that produces that product
A
Negative
feedback
Enzyme 1
B
A
Enzyme 1
B
Enzyme 2
C
C
Enzyme 3
D
D
D
D
D
D
D
D
D
D
D
Example: sugar breakdown generates ATP; excess ATP
inhibits an enzyme near the beginning of the pathway
Negative Feedback or Feedback Inhibition
Examples
a. In Feedback inhibition (a.k.a., negative feedback) is the
Inhibition of enzyme activity in which the products of a reaction
or series of reactions acts upon the enzyme(s) responsible for the
generation of that product.
b. Thus, the more product there is, the less product which is produced. If similarly, the less product
there is, the more product which is produced, then there should exist a stable product
concentration which is (or range of concentrations which are) maintained over time.
c. Feedback inhibition generally leads to well controlled metabolic pathways.
d. Your furnace and thermostat at home constitute a negative feedback system. The furnace heats
things up. At a given temperature the furnace is shut down by the thermostat. The system only
starts up again when the inhibitor (the heat) is lost from the system.
e. Example: driving at the speed limit:
i.
An analogy is driving down the highway:
1. If you are going too fast, you slow down.
http://www.northland.cc.mn.us/biology/biology1111/animations/enzyme.html
2. If you are going too slowly, you speed up.
ii. Here your velocity is the product, your car is the enzyme (gasoline and air are your substrates),
POSITIVE FEEDBACK (less common)
– The end product speeds up production
W
W
Enzyme 4
Enzyme 4
Positive
feedback
X
X
Enzyme 5
Enzyme 5
Y
Y
Enzyme 6
Z
Enzyme 6
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
Z
EXAMPLE: Chemicals released by platelets that accumulate
at injury site, attract MORE platelets to the site.
Positive Feedback Examples:
• The product of one or a series of enzymatic reactions acts upon
the enzymes responsible for the generation of that product to
increase the activity of one or more of these enzymes.
-Positive feedback can lead to out of control situations. Positive feedback tends to be
employed by life only under circumstances in which a gross over response (often
destructive) is desirable.
-A car analogy would have you accelerating even if you were already driving too fast.
-Inflammation response during injury, allergic response, bee stings are another examples.
-Positive feedback occurs durign childbirth as the pressure of the infant's head against the
exit from the womb stimulates stretch-sensitive receptors. These receptors signal for
REGULATION OF ENZYME ACTIVITY
• ALLOSTERIC REGULATION
protein’s function at one site is affected by
binding of a regulatory molecule at another site
• Allosteric regulation can
inhibit or stimulate an enzyme’s activity
Allosteric enzyme
inhibition
http://bio.winona.edu/berg/ANIMTNS/allostan.gif
SOME ALLOSTERIC ENZYMES HAVE
MULTIPLE SUBUNITS
• Each enzyme has active and inactive forms
• The binding of an
ACTIVATOR stabilizes
the active form
• The binding of an
INHIBITOR stabilizes
the inactive form
Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Stabilized active form
Cooperativity another type of allosteric activation
COOPERATIVITY
= form of allosteric regulation that can amplify
enzyme activity
Binding of one substrate to active site of one
subunit locks all subunits in active conformation
Enzyme Inhibitors
COMPETITIVE inhibitor
REVERSIBLE; Mimics substrate and
competes with substrate for active site on
enzyme
ENZYME
ANIMATION
Enzyme Inhibitors
NONCOMPETITIVE inhibitors bind to another
part of an enzyme, causing the enzyme to
change shape and making the active site less
effective
ENZYME
ANIMATION