Reginald H. Garrett
Charles M. Grisham
www.cengage.com/chemistry/garrett
Chapter 3
Thermodynamics of Biological
Systems
Reginald Garrett & Charles Grisham • University of Virginia
Essential Question
• What are the laws and principles of
thermodynamics that allow us to describe the
flows and interchanges of heat, energy, and
matter in biochemical systems?
Outline
• What are the basic concepts of thermodynamics?
• What can thermodynamic parameters tell us about
biochemical events?
• What is the effect of pH on standard-state free energies?
• What is the effect of concentration on net free energy
changes?
• Why are coupled processes important to living things?
• What characteristics define high-energy biomolecules ?
• What are the complex equilibria involved in ATP hydrolysis?
• What is the daily human requirement for ATP?
• What are reduction potentials, and how are they used to
calculate free energy changes in oxidation-reduction
reactions?
3.1 What Are the Basic Concepts of
Thermodynamics?
• Definitions for thermodynamics:
• The system: the portion of the universe
with which we are concerned
• The surroundings: everything else
• Isolated system cannot exchange matter
or energy
• Closed system can exchange energy
• Open system can exchange either or both
3.1 What Are the Basic Concepts of
Thermodynamics?
The First Law – The Total Energy of an Isolated
System is Conserved
• E (or U) is the internal energy - a function
that keeps track of heat transfer and work
expenditure in the system
• E is heat exchanged at constant volume
• E is independent of path
• E2 - E1 = ΔE = q + w
• q is heat absorbed BY the system
• w is work done ON the system
• Thus both q and w are positive when energy
flows into a system
Enthalpy
Enthalpy – a better function for constant pressure
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H = E + PV
If P is constant, ΔH = q
ΔH is the heat absorbed at constant P
Volume is approximately constant for biochemical
reactions (in solution)
• So ΔH is approximately the same as ΔE for
biochemical reactions
The Second Law –
Systems Tend Toward Disorder and Randomness
• Systems tend to proceed from ordered to
disordered states
• The entropy change for (system + surroundings)
is unchanged in reversible processes and
positive for irreversible processes
• All processes proceed toward equilibrium - i.e.,
minimum potential energy
Entropy
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A measure of disorder
An ordered state is low entropy
A disordered state is high entropy
dSreversible = dq/T
“What is Life?”, asked Erwin Schrödinger, in 1944.
A disorganized array of
letters possesses no
information content and is a
high-entropy state,
compared to the systematic
array of letters in a
sentence.
Erwin Schrödinger’s term
“negentropy” describes the
negative entropy changes
that confer organization and
information content to living
organisms. Schrödinger
pointed out that organisms
must “acquire negentropy”
to sustain life.
Energy dispersion
• Entropy can be defined as S = k ln W
• And ΔS = k ln Wfinal – k ln Winitial
• Where Wfinal and Winitial are the final and initial
number of microstates of a system, and k is
Boltzmann’s constant.
• Viewed in this way, entropy represents energy
dispersion – the dispersion of energy among a large
number of molecular motions relatable to quantized
states (microstates).
• The definition of entropy above is engraved on the
tombstone of Ludwig Boltzmann in Vienna, Austria
The Third Law –
Why Is “Absolute Zero” So Important?
• The entropy of any crystalline, perfectly ordered
substance must approach zero as the temperature
approaches 0 K
• At T = 0 K, entropy is exactly zero
• For a constant pressure process:
Cp = dH/dT
Free Energy
• Hypothetical quantity - allows chemists to asses
whether reactions will occur
• G = H - TS
• For any process at constant P and T:
ΔG = ΔH - TΔS
• If ΔG = 0, reaction is at equilibrium
• If ΔG < 0, reaction proceeds as written
G and Go´ - The Effect of Concentration on ΔG
• How can we calculate the free energy
change for reactions not at standard state?
• Consider a reaction: A + B  C + D
• Then:
æ [C][D] ö
DG = DG + RT ln ç
è [ A][B] ÷ø
• Thus concentrations at other than 1 M will
change the value of ΔG
ΔG° Can Be Temperature Dependent
ΔS° Can Be Temperature Dependent
3.3 What is the Effect of pH on Standard
State Free Energies?
• A standard state of 1 M for H+ is not typical for
biochemical reactions.
• It makes more sense to adopt a modified standard
state – i.e., 1 M for all constituents except protons,
for which the standard state is pH 7.
• This standard state is denoted with a superscript
“°”
• For reactions in which H+ is produced:
ΔG°´= ΔG° + RT ln [H+]
• And for reactions in which H+ is consumed:
ΔG°´ = ΔG° - RT ln [H+]
3.4 What Can Thermodynamic Parameters
Tell Us About Biochemical Events?
• A single thermodynamic parameter is not very useful
• Comparison of several thermodynamic parameters
can provide meaningful insights about a process
• Heat capacity values can be useful
• A positive heat capacity change for a process
indicates that molecules have acquired new ways to
move (and thus to store heat energy)
• A negative heat capacity change means that the
process has resulted in less freedom of motion for
the molecules involved
3.4 What Can Thermodynamic Parameters
Tell Us About Biochemical Events?
Unfolding of a soluble protein exposes significant numbers of
nonpolar groups to water, forcing order on the solvent and
resulting in a negative entropy change.
3.4 What Can Thermodynamic Parameters
Tell Us About Biochemical Events?
3.5 What are the Characteristics of HighEnergy Biomolecules?
Energy Transfer - A Biological Necessity
• Energy acquired from sunlight or food must be used
to drive endergonic (energy-requiring) processes in
the organism
• Two classes of biomolecules do this:
• Reduced coenzymes (NADH, FADH2)
• High-energy phosphate compounds – with free
energy of hydrolysis more negative than -25
kJ/mol
High-Energy Biomolecules
Table 3.3 is important
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Note what's high - PEP and 1,3-BPG
Note what's low - sugar phosphates, etc.
Note what's in between - ATP
Note difference (Figure 3.6) between overall
free energy change - noted in Table 3.3 - and
the energy of activation for phosphoryl-group
transfer
3.5 What are the Characteristics of HighEnergy Biomolecules?
3.5 What Are the Characteristics of HighEnergy Biomolecules?
The activation energies
for phosphoryl group
transfer reactions are
substantially larger
than the free energy of
hydrolysis of ATP.
Group Transfer Potentials Quantify the
Reactivity of Functional Groups
Group transfer is analogous to ionization potential and
reduction potential. All are specific instances of free
energy changes.
ATP
An Intermediate Energy Shuttle Device
• PEP and 1,3-BPG are created in the course of
glucose breakdown
• Their energy (and phosphates) are transferred
to ADP to form ATP
• But ATP is only a transient energy carrier - it
quickly passes its energy to a host of energyrequiring processes
ATP Contains Two Pyrophosphate Linkages
ATP contains two pyrophosphate linkages.
The hydrolysis of phosphoric acid anhydrides
is highly favorable.
Phosphoric Acid Anhydrides
How ATP does what it does
• ADP and ATP are examples of phosphoric
acid anhydrides
• Note the similarity to acyl anhydrides
• Large negative free energy change on
hydrolysis is due to:
• electrostatic repulsion
• stabilization of products by ionization and
resonance
• entropy factors
Ionization States of ATP
• ATP has four dissociable protons
• pKa values range from 0-1 to 6.95
• Free energy of hydrolysis of ATP is relatively
constant from pH 1 to 6, but rises steeply at high pH
• Since most biological reactions occur near pH 7, this
variation is usually of little consequence
3.6 What Are the Complex Equilibria
Involved in ATP Hydrolysis?
The Effect of Concentration
Recall that free energy changes are concentrationdependent
So the free energy available from ATP hydrolysis
depends on concentration
• We will use the value of −30.5 kJ/mol for the standard
free energy of hydrolysis of ATP
• At non-standard-state conditions (in a cell, for
example), the ΔG is different
• Equation 3.13 allows the calculation of ΔG - be sure
you can use it properly
• In typical cells, the free energy change for ATP
hydrolysis is typically −50 kJ/mol
3.7 Why Are Coupled Processes Important
to Living Things?
• Many reactions of cells and organisms run against
their thermodynamic potential – that is, in the
direction of positive ΔG
• Examples – synthesis of ATP, creation of ion
gradients
• These processes are driven in the
thermodynamically unfavorable direction via
coupling with highly favorable processes
3.8 What is the Daily Human Requirement
for ATP?
• The average adult human consumes approximately
11,700 kJ of food energy per day
• Assuming thermodynamic efficiency of 50%, about
5860 kJ of this energy ends up in form of ATP
• Assuming 50 kJ of energy required to synthesize one
mole of ATP, the body must cycle through 5860/50
or 117 moles of ATP per day
• This is equivalent to 65 kg of ATP per day
• The typical adult human body contains 50 g of
ATP/ADP
• Thus each ATP molecule must be recycled nearly
1300 times per day
ATP Changes Keq by 108
• Consider a process: A → B
• Compare this to A + ATP → B + ADP + Pi
• Assuming typical cellular concentrations of ATP,
ADP and Pi, and using the cellular free energy
change for ATP hydrolysis, it can be shown that
coupling ATP hydrolysis to the reaction of A → B
changes the equilibrium ratio of B/A by more than
200 million-fold
3.9 What Are Reduction Potentials?
How Are Reduction Potentials Used to Calculate
Free Energy Changes for Oxidation-Reduction
Reactions?
High ℰo' indicates a strong tendency to be reduced
• Crucial equation: ΔGo' = −nℱΔℰo'
Δℰo' = ℰo'(acceptor) - ℰo'(donor)
• Electrons are donated by the half reaction with the
more negative reduction potential and are
accepted by the reaction with the more positive
reduction potential: Δℰo ' positive, ΔGo' negative
• If a given reaction is written so the reverse is true,
then the Δℰo' will be a negative number and ΔGo'
will be positive
3.9 What Are Reduction Potentials?
The standard reduction potential difference describing
electron transfer between two species:
Is related to the free energy change for the process by:
ΔGo' = −nℱΔℰo'
Where n represents the number of electrons transferred, ℱ
is Faraday’s constant, and Δℰo‘ is the difference in
reduction potentials between the donor and acceptor.
Questions
• 1-6, 8,10-11, 18