Download Today: Membrane Structure continued Membrane Transport Exam

Thinking
About
Energy
and
Enzymes
Case Study: Frank


Frank’s aldehyde dehydrogenase
(ALDH) enzyme has a substitution at
position 487. He has the amino acid
lysine at this position instead of
glutamic acid.
You Try: Question 1
Metabolism
Metabolism = all
an organism’s
chemical
reactions
An emergent
property!
Metabolism Overview
Notice
that this is
an open
system!
What is Energy?
Energy: Capacity to Do Work
1.
Kinetic Energyenergy of movement
2.
Potential Energyenergy due to location/structure
3.
Chemical Energyresult of arrangement of atoms in molecules
(potential energy in disguise!!)
First Law of Thermodynamics
?
First Law of Thermodynamics
Energy can be
transferred and
transformed, but
not created or
destroyed.
What has Escher
done??
Second Law of Thermodynamics
?
Second Law of Thermodynamics
Every energy
transfer
increases the
ENTROPY of the
universe
Thermodynamics
The quantity of energy in the universe is
constant, but the quality is not!
Life is
Ordered…
Does this violate
the second law of
thermodynamics?
Life is
Ordered…
No! Life exists at
the expense of
free energy.
Free Energy (G)


Ordered
states (at left)
have high free
energy, or
energy
available to
do work
Disordered
states (high
entropy) have
low free
energy.
Free Energy (G)
Total Energy = usable energy + unusable energy
Enthalpy (H)
Free Energy (G)
or
H=G+TS
G=H–TS
Entropy (S)
More on Free Energy
delta G = G final state – G starting state
For a process to occur spontaneously, the
system must either lose energy (decrease H) or
lose order (increase S)
This results in a negative value for
Free Energy (G) in Metabolism
Metabolic reactions can be classified as
either:
EXERGONIC
OR
ENDERGONIC
“Energy Outward”
“Energy inward”
Negative delta G
Positive delta G
Spontaneous
Not Spontaneous!
You Try: Question 2
Closed Systems Reach Equilibrium:
What happens
if we reach
equilibrium?!?
Organisms are Open Systems!
= “Metabolic Disequilibrium”
Revisiting ATP
Revisiting ATP
ATP does work by phosphorylating
intermediates. Phosphorylation usually
makes a molecule less stable/more
reactive.
Example:
Enzymes
The Chemistry of Life is driven by more than
Thermodynamics!
This is a spontaneous (negative delta G) reaction! So…
1. Why doesn’t table sugar break down into
glucose and fructose in our kitchens?
2. Why does sucrose break down so easily in
organisms?
Activation Energy
Enzymes Lower Activation
Energy Barrier
Enzymes: Key Features




Biological Catalysts- Enzymes can
increase the rate of a reaction, but
does not change the delta G!
Enzymes are specific, and typically only
recognize one particular substrate
Substrates interact with active sites on
the enzyme as described by the
induced fit model
Enzymes are affected by their
environment
Enzyme Function
Enzymes: Induced Fit
Mechanisms for Enzyme
Function



Enzymes can orient substrates
Enzymes can induce strain in the
substrate
Enzymes can temporarily add
chemical groups to substrates
Acid-base catalysis
 Covalent catalysis
 Metal ion catalysis

An Enzyme’s
ACTIVITY
is generally
OPTIMIZED
for its
Environment
How does this
arise??
Thinking About Simple
Enzyme Kinetics
You try: Question 3
Many Enzymes Require
COFACTORS or
COENZYMES: Vitamin C
(ascorbate) is a Coenzyme
The
hydroxylation of proline residues in
collagen requires ascorbate.
Vitamin C is, therefore, required for the
maintenance of normal connective tissue as
well as for wound healing.
Vitamin C also is necessary for bone
remodeling due to the presence of collagen
in the organic matrix of bones.
Enzymes: Regulation
Enzyme Inhibitors- Molecules that
selectively inhibit the activity of specific
enzymes
Competitive
Inhibitors
Noncompetitive
Inhibitors
Block substrates from
entering active site
Bind to another
region of the enzyme,
changing the shape
of the enzyme and
limiting or preventing
its activity
Enzyme Inhibitors
Competitive
Inhibition
Normal
Function
Noncompetitive
Inhibition
Cool Things To Do With Enzyme Inhibitors:
Design Drugs
Figure: COX 1 and 2 : The cyclo-oxygenase systems by drdoc on-line ©
Other Mechanisms:
Allosteric Regulation
Regulatory molecules may bind weakly to an
allosteric enzyme, changing its shape and
function
Other Mechanisms:
Allosteric Regulation
Allosteric
Regulation
Often Explains
Feedback
Inhibition:
One Last Mechanism: Cooperativity
The binding of one molecule of substrate to
an allosteric enzyme may trigger a
favorable conformational change in the
other subunits
Thinking Ahead to Lab
Our Model System:
Oxidation of Catechol
(catalyzed by Catecholase)
Factors that might affect the rate of
this reaction?
How will we know if our enzyme
is working and/or affected by its
environment?
Introducing Your Reagents:
“Potato Juice” =
Enzyme Solution!
Thinking About Good Experimental Design

What is a ‘control’? What does it tell me about my
experiment?

What would a good control be for this experiment?
With your lab group, complete the Prelab Sheet:
1) Identify factors that might affect enzyme function
(generate hypotheses!)
2) Decide which factor you would like to test
3) Design your experiment!