Free Energy and Catalysis

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Free Energy and Catalysis

• Free energy
• ATP
• Enzymes coupling and catalysis
• Enzymes inhibition and regulation

Alec Hodel 10/4/01
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Thermodynamics Free Energy
Life is like a ball rolling down a hill. The
hill Free Energy The ball everything All
balls tend to roll down hill.
Free Energy
All things tend to fall into the state of lowest
free energy.
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Free Energy GChange in Free Energy DG
High G state - High energy - unstable.
Moving down, DG is negative, Favorable
Moving up, DG is positive, unfavorable - cant
do it without help.
Free Energy
Happiest of all - Lowest Free energy
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What is this Free energy?
Free energy is a combination of two
factors Enthalpy DH How much heat is
absorbed Entropy DS How much order is
produced DG DH - T DS Where T is the
temperature. Thus, for the ball to roll
downhill, it must release heat and/or become more
disordered.
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Some real life examples
High energy Carbohydrates, fats, oxygen
Our bodies work by converting high energy food
into low energy compounds and using that released
energy to perform its biological functions
Free Energy
Low energy CO2, H2O
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Free energy changes in a reaction
A B
In the reaction above, the free energy of the
reaction is
Where Keq is the equilibrium constant for the
reaction. This constant describes the direction
the reaction will go in a given condition.
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The Equilibrium Constant
At equilibrium, DG0. Thus,
Keq describes the ratio of B to A at
equilibrium. Thus
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But doesnt life go backwards?
Proteins, DNA, RNA
Yet our bodies seem to work in the opposite
direction we take simple molecules and make
large complex structures out of them.
Free Energy
Amino acids, nucleotides.
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The secret coupling reactions together.
The reaction is favorable as long as the total DG
is negative.
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We burn food to make ourselves.
Food O2
Protein
Catabolism of food is coupled to anabolic
biosynthesis and the other processes of life.
Free Energy
Amino Acids
CO2 H2O
Total DG is negative - Life is a favorable
reaction!
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ATP - The Petrol of Life
For convenience, energy from catabolism is
usually stored as chemical energy in a
high-energy intermediate. Everybodys favorite is

High energy phosphate bonds.
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Enzymes Coupling and Catalysis
Enzymes are proteins that orchestrate the
multitudes of reactions that occur in our body.
They perform two main functions in a chemical
reaction Coupling - They often couple favorable
reactions with unfavorable reactions. Example
Couple ATP hydrolysis to peptide
synthesis. Catalysis - They increase the rate of
a specific reaction dramatically over the
spontaneous rate.
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Enzymes
Most of what we do is take the stuff we eat and
convert all the small molecules in the food into
biomolecules and energy. Each of the steps in
these metabolic pathways is catalyzed by
enzymes.
Dont memorize this..
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Enzymes
Enzymes catalyze a variety of chemical reactions
in pathways localized throughout the cell.
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Properties of Enzymes

• Active Site
• Is complementary in shape and functionality with
  the substrate.
• Catalytic Efficiency
• Rate increased 103-108
• Specificity
• Reactions are extremely specific in both the
  substrates and the products.
• Regulation

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Catalysis and Kinetics - How long does it take?
A ball may want to go downhill, but that doesnt
mean it can do it quickly. The ball may have to
roll over a hill to get to the valley. Often you
cant get there from here without some help.
Transition State Activation Energy
Free Energy
For example, sugar does not spontaneously combust
into CO2 (except on the X-files).
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Catalysis
Catalysis is defined as reducing the energy
barrier between the reactants and the
products. Catalysis does not change the relative
free energies of the reactants and products.
Free Energy
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Catalysis
Enzymes do not force a reaction or provide energy
for a reaction. As catalysts, they simply poise
all the reactants in a arrangement that allows
the reaction to proceed more rapidly than it
would otherwise.
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Michaelis-Menten Equation
E S ? ES ? E P
Simple reaction gives a hyperbolic curve for the
rate of the reaction vs. the substrate
concentration. Km reflects the affinity for the
substrate. Vmax reflects the rate of catalysis
and the concentration of enzyme.
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The MM equation gets simple at the extremes.
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Why does this matter?
In Liver, For when you eat
In all cells, For minute to minute energy
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Regulation Inhibition

• Competitive Inhibition
• Inhibitor competes with substrate for binding to
  enzyme
• Example Product inhibition
• Weve made enough, now cut it out!

E S ? ES ? E P
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Effect of Competitive Inhibition
Competitive inhibitors increase the effective Km
of the substrate - That is they decrease the
effective affinity of the enzyme for the
substrate.
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Regulation Inhibition

• Noncompetitive Inhibition
• Inhibitor inactivates the enzyme by binding to a
  site different than the substrate-binding site.

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Effects of Noncompetitive Inhibition
Noncompetitive inhibition inactivates a pool of
the enzyme - Thus reducing the effective
concentration of the enzyme.
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Regulation Cooperativity
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Regulation of Pathways
High concentrations of a downstream product of a
pathway signals an upstream enzyme to shut down.
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Regulation Modification of the enzyme
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Now, what did we learn today?

• Free energy and whether a reaction is favorable
• Equilibrium constants and the direction of a
  reaction
• Coupling of reactions
• ATP
• Catalysis and enzymes
• Km vs Vmax in an enzyme reaction
• Competitive and noncompetitive inhibition.