BIOENERGETICS

Bart Dzudzor
 Lecture Objectives:
• Be able to identify energy sources and there utilization.
• Be able to understand how Endergonic processes
proceed by Coupling to Exergonic processes.
• Be able to predict the spontaneity of biochemical
reactions based on the signs of ΔG, ΔH and ΔS.
• Be able to calculate standard free energy changes of
biochemical reactions given the equilibrium constant and
vice versa.
• How high-energy phosphates (ATP) play a central role in
energy capture and transfer and also acts as the “energy
currency” of the cell.
 Some Biomedical Importance of
Bioenergetics
* Bioenergetics, or biochemical thermodynamics, is the
study of the energy changes accompanying biochemical
reactions.
* Death from starvation occurs when available energy
reserves are depleted.
* Certain forms of malnutrition are associated with energy
imbalance (marasmus).
* Thyroid hormones control the rate of energy release
(metabolic rate), and disease results when they
malfunction.
* Excess storage of surplus energy causes obesity, one of
the most common diseases of Western society.
 Introduction to Metabolism
Metabolism = the sum of all chemical
reactions that take place
in a cell or organism.

Bioenergetics = the quantitative study of

the energy transductions that occur in
in living cells and the nature and function
of the chemical processes underlying these
transductions.
 What do cells and organism use
their energy to do?
• Cells need energy for several cellular processes
including;
• motility
• pumping of molecules across membranes
• maintaining temperature
• cell growth and division
• secreting molecules
• sending signals to one another
• synthesizing or degrading macromolecules
• energy to do work, etc
Sources of energy
• Catabolic pathways generally converge
• Anabolic pathways diverge
• Some pathways are cyclic
Overview of catabolism Complex

Monomeric unit
Glycolysis
Acetyl-Coenzyme A

Learn to
c ogni z e this
re
molecule
 E1 E2 E3
Principles of Metabolic Regulation
A ∆G1
B ∆G2
C D
∆G3
General features of metabolic pathways:
• Individual reaction steps may be reversible, but the overall
pathway is irreversible.

• The irreversible committed step is usually an early reaction step.

(∆ G1 << 0)

• The rate of metabolism (flux) through a pathway is regulated at

the committed reaction step (rate-limiting step).

• Opposing degradation/biosynthetic pathways that proceed through

the same metabolites must differ in at least one enzyme to allow
for independent regulation in each direction. (Often referred to as
“coordinated control” or “reciprocal regulation”.)

• The enzymes that mediate a given reaction pathway are found in

the same cellular compartment or organelle.
Glycolysis

The irreversible committed step is usually

an early reaction step. (∆G1 << 0)
The enzymes that mediate a given reaction pathway are found
in the same cellular compartment or organelle
 II. How are reaction steps regulated?
A. Enzyme amount (esp. procaryotes)
1. Transcription
2. Translation
3. mRNA stability
4. Protein stability (degradation)

B. Enzyme activity (positive or negative effectors)

1. Metabolites
2. Active site inhibitors
3. Allosteric modulators
4. [ATP]/[ADP] energy status
5. [NADH]/[NAD+] reduction status
6. Covalent modification of enzyme
(phosphorylation)
III. Regulation by metabolites within the same pathway

A. Simple feedback inhibition

B.Complex feedback inhibition

1. Cumulative
2. Concerted
3. Sequential
4. Isoenzymes for multiple effectors
 Laws of Thermodynamics
• The first law of thermodynamics states that the total
energy of a system, including its surroundings,
remains constant.

• It implies that within the total system, energy is neither

lost nor gained during any change.

• However, energy may be transferred from one part of the

system to another or may be transformed into another
form of energy.

• In living systems, chemical energy may be transformed

into heat or into electrical, radiant, or mechanical energy.

• Energy-utilizing reactions perform various necessary

and, in many instances, tissue-specific, cellular
functions, for example, nerve impulse conduction,
muscle contraction, growth, and cell division.
 Laws of Thermodynamics cont’d.
• The second law of thermodynamics states that
the total entropy of a system must increase
if a process is to occur spontaneously.

• Entropy is the extent of disorder or

randomness of the system and becomes
maximum as equilibrium is approached.
Biological Systems Obey the Physical
Laws of Thermodynamics

∆ G=∆ H-
T∆ S
∆ H = ∆ U + P∆ V
G = Gibbs Free Energy
H = Enthalpy
S = Entropy
U = Internal Energy
 Free Energy
• Hypothetical quantity - allows chemists to asses whether reactions will
occur

• The Gibbs free energy: G = H - TS

• For any process at constant P and T:

∆ G = ∆ H - T∆ S
If ∆ G = 0, reaction is at equilibrium
If ∆ G < 0, reaction proceeds as written

Exergonic:
Spontaneous processes with negative (-) ∆ G

Endergonic:
Processes that are not spontaneous with positive (+) ∆ G
 Variation of Reaction Spontaneity (Sign of ∆ G)
with the signs of ∆ H and ∆ S
Page 56
 Free Energy Calculations:
enzyme

aA + bB cC + dD , ∆Grxn
c d
[C] [D]
Standard free E change at pH 7 ∆G = ∆ G'o + RT ln [A]a [B]b
Biochemists use this

∆ G < 0, product formation is favored

∆ G = 0, reaction at equilibrium
∆ G > 0, substrate formation favored
c d
[C] [D]eq
At equilibrium, ∆G'o = -RT ln [A] [B]b eq
a
eq eq

If all [i] = 1 M, ∆G = ∆G'o

Standard free E change under standard conditions
pH 0, 1 atm pressure &
When recatants & products are present initially at 1 M
Living systems can couple energy requiring reactions to
those which are spontaneous (exergonic)
A chemical example of reaction coupling
 Some coupled reactions involving ATP

Exergonic reaction drives the endergonic processes

 Reasons why Certain compounds or
Bonding arrangements are energy rich
1. Products of hydrolysis of an energy-rich bond may exist in more resonance forms
than the precursor molecule.
• The more possible resonance forms in which a molecule can exist stabilize that
molecule. Eg. Fewer resonance forms can be written for ATP or PPi than for Pi.
2. Many high-energy bonding arrangements have groups of similar electrostatic charges
located in close proximity to each other in such compounds.
• Because like charges repel one another, hydrolysis of energy-rich bonds alleviates
this situation lending stability to products of hydrolysis.
3. Hydrolysis of certain high-energy bonds results in formation of an unstable compound
which may isomerize spontaneously to form a more stable compound. ΔGo’ for
isomerization is considerable, and the final product is much more stable. e.g. PEP
enolpyruvate to pyruvate.
4. If a product of hydrolysis of a high-energy bond is an undissociated acid, dissociation
of the proton and its subsequent buffering may contribute to the overall ΔGo’ of the
hydrolytic reaction.
In general, any property or process that lends stability to products of hydrolysis tends to
confer a high-energy character to that compound.
 Adenosine triphosphate (ATP)

High-energy bonds
Why is ATP a “high-energy” compound ?
 ATP is
kinetically
very
stable

ATP + H2O
Slow reaction

ADP + HPO42-
Garrett & Grisham
ATP in water is not readily converted Fig. 3.8
to ADP, but needs enzymes to mediate hydrolysis.
ATP the universal energy carrier

It releases a significant amount of free energy upon hydrolysis.

But not too much so it can be a between “high energy”
phosphate donors and low energy acceptors.
Why are the hydrolysis products (ADP+Pi) more stable than the reactant (ATP)?

(1) More resonance forms per phosphate in hydrolysis products

ATP
* More possible forms a molecule can exist
stabilizes the molecule
* Pi has more resonance forms than ATP

ADP Pi
(2) Charge separation in products
Similar electrostatic charges close
together in ATP compared to products
Creatine
Hydrolysis of energy rich compound can form an unstable compound
but can isomerize spontaneously to form stable compund

Stable form

Spontaneous isomerization
Consider a reaction: A + B C
Then:
∆ G = ∆ Go + RT ln ([C]/[A][B])
∆ Go = free energy change of the reaction under standard conditions

∆ Go used in physical chemistry

∆ Go' used in biochemistry

In "Chemistry":
The standard state convention defines the standard state of
solute as that with unit activity at 25oC and 1 atm. (So if H+ is a
reactant or product, pH = 0.)

In "Biochemistry":
The standard state convention is modified because most
reactions occur in dilute solutions near pH 7 with activities of
water and proton at unity

Remember that ∆ G = ∆ G'

 Free energy change is dependent on concentration

∆ G Actual free energy change under specified

conditions, including concentration of
reactants and products

∆ G0 Standard Free energy change, all reactants

and products in their standard states, i.e.
1 M concentration.

Unfortunately, if [H+] = 1 M, pH = 0, which is

not consistent with biochemical processes.

∆ G0' Standard Free Energy change for the

biochemical standard state, all reactants and
products at 1 M

except

[H+] = [OH-] = 10-7 M, which allows pH = 7.

standard transformed constants
 Free Energy Calculations:
enzyme

aA + bB cC + dD , ∆Grxn
c d
[C] [D]
Standard free E change at pH 7 ∆G = ∆ G'o + RT ln [A]a [B]b
Biochemists use this

∆ G < 0, product formation is favored

∆ G = 0, reaction at equilibrium
∆ G > 0, substrate formation favored
c d
[C] [D]eq
At equilibrium, ∆G'o = -RT ln [A] [B]b eq
a
eq eq

If all [i] = 1 M, ∆G = ∆G'o

Standard free E change under standard conditions
pH 0, 1 atm pressure &
When reactants & products are present initially at 1 M
1) Calculate the equilibrium constant for the hydrolysis of
glucose-1-phosphate at 37oC.

c d
[C] [D]
∆G = ∆G' o + RT ln [A]a [B]b
K
c d
[C] [D]
∆G'o = -RT ln [A] [B]eqb
eq
a
eq
eq

From table ∆Go’ = - 20.9 kJ.mol-1

@ equilibrium ∆ G = 0

Answer: K = 3300
Consider a reaction: A + B C
Go = free energy change of the reaction under standard conditions

∆ G = ∆ Go + RT ln Keq

∆ G = ∆ Go + RT ln([C]/[A][B])

At equilibrium, ∆ G = 0

Therefore, ∆ Go = - RT ln Keq = - RT ln ([C]/[A][B])

Thus the equilibrium constant can be calculated from standard

free energy data and vice versa.
 Free energy change can be very different from standard
state if concentration of reactant and product are
Phosphocreatine + Hunit
different from 2O activityCreatine
(1 M) + Pi

∆ Go' at 37oC = - 43.1 kJ/mol

Physiological concentrationsof phosphocreatine, creatineandPiarebetween1and10

mM.

Assuming1mMconcentrationandusingequation

∆ G = ∆ Go' + RT ln ([C][D]/[A][B])
∆ G = - 43.1 kJ/mol + (8.314 J/mol. K) (310 K) ln ([0.001][0.001]/[0.001])

∆ G = - 60.9 kJ/mol

Difference between standard state and 1 mM concentration for the

 Variation of Keq with ∆ G° at 25°C

-
-
-
-
Page 57
Free Energies of Formation of Some Compounds
of Biochemical Interest
Page 58
Page 58
Consider a reaction: A + B C
Go = free energy change of the reaction under standard conditions

∆ G = ∆ Go + RT ln Keq

∆ G = ∆ Go + RT ln([C]/[A][B])

At equilibrium, ∆ G = 0

Therefore, ∆ Go = - RT ln Keq = - RT ln ([C]/[A][B])

Thus the equilibrium constant can be calculated from standard

free energy data and vice versa.
Many biological reactions lead to an increase
in order (decrease in entropy)

Linking of individual amino acids

Protein Cells cope this situation by

coupling this reaction to a
highly negative ∆ G reaction
 An unfavorable reaction can proceed
spontaneously if it is coupled to an
energetically favorable reaction

A B + X ∆ G = + 50 kJ/mol
X Y + Z ∆ G = -100 kJ/mol

Overall reaction: A B + Y + Z

∆ G = - 50 kJ/mol
Values from human erythrocytes

PEP + H2O Pyruvate + Pi ∆ G = -78 kJ/mol

ADP + Pi ATP + H2O ∆ G = 55 kJ/mol

PEP + ADP Pyruvate + ATP Total ∆ G = -23 kJ/mol