Chapter 6: An Introduction to Metabolism

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Chapter 6An Introductionto Metabolism
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Metabolism (Overview)

• Metabolism Catabolism Anabolism
• Catabolic reactions are energy yielding
• They are involved in the breakdown of
  more-complex molecules into simpler ones
• Anabolic reactions are energy requiring
• They are involved in the building up of simpler
  molecules into more-complex ones
• We can consider these bioenergetics in terms of
  the physical laws of thermodynamics

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1st 2nd Laws of Thermodynamics
Every energy transfer or transformation
increases the disorder (entropy) of the
universe. p. 143, Campbell Reece (2005) Note
especially the waste heat
Energy can be transferred or transformed but
neither created nor destroyed. p. 143, Campbell
Reece (2005)
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Organisms are Energy Transducers

• Organisms take in energy transduce (change) it
  to new forms (1st law)
• As energy transducers, organisms are less than
  100 efficient (2nd law)
• Organisms employ this energy to
• Grow
• Protect Themselves
• Repair Themselves
• Compete with other Organisms
• Make new Organisms (I.e., babies)
• In the process, organisms generate waste
  chemicals heat
• Organisms create local regions of order at the
  expense of the total energy found in the
  Universe!!! We are Energy Parasites!

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Water Fall Analogy
Get it?
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Laws of Thermodynamics

• First Law of Thermodynamics
• Energy can be neither created nor destroyed
• Therefore, energy generated in any system is
  energy that has been transformed from one state
  to another (e.g., chemically stored energy
  transformed to heat)
• Second Law of Thermodynamics
• Efficiencies of energy transformation never equal
  100
• Therefore, all processes lose energy, typically
  as heat, and are not reversible unless the system
  is open the lost energy is resupplied from the
  environment
• Conversion to heat is the ultimate fate of
  chemical energy

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Movements Toward Equilibrium
Increase stability
Downhill
?G lt 0
Greater entropy
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Entropy!
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Free Energy Spontaneity
What is the name of this molecule?
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Movement Toward Equilibrium
Work
Equilibrium
Potential energy
Spontaneous
Forward reaction
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Movement Toward Equilibrium
Viable organisms exist in a chemical
disequilibrium that is maintained via the
harnessing of energy obtained from the organisms
environment (e.g., you eat to live)
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Waterfall Analogy
Potential Energy
Really
Kinetic Energy
Stayring of a turbine generator, Priest Rapids
Dam, 1958
Waste Heat (once reaches Bottom)
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Movement Toward Equilibrium
Spontaneous
Food
Potential energy
Waste heat
Forward reaction
Work
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Movement Toward Equilibrium in Steps
Note that Spontaneity is not a measure of speed
of a process, only its direction
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Exergonic Reactions
Food
Energy released
Movement toward equilibrium
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Endergonic Reactions
Work
Energy required
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Exergonic Reaction (Spontaneous)

• Decrease in Gibbs free energy (-?G)

• Increase in stability

• Spontaneous (gives off net energy upon going
  forward)

• Downhill (toward center of gravity well, e.g.,
  of Earth)

• Movement towards equilibrium

• Coupled to ATP production (ADP phosphorylation)

• Catabolism

Endergonic Rxn (Non-Spontaneous)

• Increase in Gibbs free energy (?G)

• Decrease in stability

• Not Spontaneous (requires net input of energy to
  go forward)

• Uphill (away from center of gravity well, e.g.,
  of Earth)

• Movement away from equilibrium

• Coupled to ATP utilization (ATP
  dephosphorylation)

• Anabolism

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Coupling Reactions
Minus the cut for the 2nd law
Exergonic reactions can supply energy for
endergonic reactions
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Energy Coupling in Metabolism
Catabolic reactions provide the energy that
drives anabolic reactions forward
Catabolic reaction
Anabolic reaction
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Adenosine Triphosphate (ATP)
Call this A
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Energy Coupling via ATP
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Hydrolysis of ATP
Movement toward equilibrium
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Coupled Reactions
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How that reaction really works
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Various Pi Transfers
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Summary of Metabolic Coupling
Exergonic reaction
Endergonic reaction
Exergonic reaction
Endergonic reaction
Get it? Exergonic processes drive Endergonic
processes
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Movement Toward Equilibrium
Food
Endergonic
Exergonic
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Coupling the Biosphere
Anabolic process
Catabolic process
Chemically stored energy
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Enzyme Catalyzed Reaction
Question Is this reaction endergonic or is it
exergonic?
Enzyme
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Activation Energy (EA)
Anything that doesnt require an input of energy
to get started has already happened!
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Low- (i.e., body-) Temp. Stability

• Why don't energy-rich molecules, e.g., glucose,
  spontaneously degrade into CO2 and Water?
• To be unstable, something must have the potential
  to change into something else, typically
  something that possesses less free energy (e.g.,
  rocks)
• To be unstable, releasing somethings ability to
  change into something else must also be
  relatively easy (i.e., little input energy)
• Therefore, stability already low free energy
• Alternatively, stability high activation energy
• Things, therefore, can be high in free energy but
  still quite stable, e.g., glucose

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Catalysis
Lowering of activation energy
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Catalysis
This is instead of adding heat heat is an
inefficient means of speeding up reactions since
it simply is a means of increasing the random
jostlings of molecules
At a given temperature, catalyzed reactions can
run faster because less energy is required to
achieve the transition state
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Enzyme-mediated Catalysis
Subtle application of energy
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Mechanisms of Catalysis

• Active sites can hold two or more substrates in
  proper orientations so that new bonds between
  substrates can form
• Active sites can stress the substrate into the
  transition state
• Active sites can maintain conducive physical
  environments (e.g., pH)
• Active sites can participate directly in the
  reaction (e.g., forming transient covalent bonds
  with substrates)
• Active sites can carry out a sequence of
  manipulations in a defined temporal order (e.g.,
  step A ? step B ? step C)

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Catalysis as Viewed in 3D
The rest of an enzyme is involved in supporting
active site, controlling reaction rates,
attaching to other things, etc.
Active site is site of catalysis
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Induced Fit (Active Site)
Induced fit not only allows the enzyme to bind
the substrate(s), but also provides a subtle
application of energy (e.g., bending chemical
bonds) that causes the substrate(s) to
destabilize into the transition state
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Enzyme Saturation
Enzyme Activity at Saturation is a Function of
Enzyme Turnover Rate
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Enzyme Saturation
Turnover rate
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Non-Specific Inhibition of Enzyme Activity
Reduced rate of chemical reaction
Instability shape change (too fluid)
Reduced enzyme fluidity
Denatured?
Turnover rate
Change in R group ionization
Change in R group ionization
Even at saturation, rates of enzymatic reactions
can be modified
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Activators of Catalysis
Dont worry about apoenzyme and holoenzyme
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Specific Inhibition
Competitive inhibitors can be competed off by
supplying sufficient substrate densities
Non-competitive inhibitors cannot be competed off
by substrate
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Allosteric Interactions
Reversible interactions, sometimes on, sometimes
off, dependent on binding constant and density of
effector
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Cooperativity
Cooperativity is when the activity of other
subunits are increased by substrate binding to
one subunits active site
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Feedback Inhibition
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Energy-Metabolism Regulation
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Enzyme Localization
Organization of Electron Transport Chain of
Cellular Respiration Substrate ? Enzyme ?
Product ? Enzyme chains are co-localized
Enzymes in single pathway may be co-localized so
that the product of one enzyme increases the
local concentration of the substrate for another
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The End