Bioenergetics is the quantitative study of energy transformations that occur in living cells. It concerns the initial and final energy states of biochemical reactions, not reaction rates. The goal is to describe how organisms acquire and transform energy to perform biological work. Reactions are classified as exergonic (energy releasing) or endergonic (energy consuming). Gibbs free energy determines the direction of reactions. It is related to enthalpy, entropy, and temperature based on the equation ΔG = ΔH - TΔS. Redox potential is a quantitative measure of an element or compound's ability to oxidize or reduce. It indicates the tendency of chemical species to gain or lose electrons in redox reactions.

1. BIOENERGETICS
DEVIPRIYA PV
M PHARM

2. CONTENTS
 Concept of free energy, endergonic and exergonic reaction, Relationship
between free energy, enthalpy and entropy; Redox potential.
 Energy rich compounds; classification; biological significances of ATP and
cyclic AMP

3. BIOENERGETICS
 Bioenergetics or biological thermodynamics is the
quantitative study of energy transductions (changes of
one form of energy into another)that occur in living cells,
and of the nature and function of the chemical processes
underlying these transductions.
 ie. Bioenergetics deals with the study of energy changes
(transfer and utilization ) in biochemical reactions

4. BIOENERGETICS
 Bioenergetics concerns only the initial and final energy
states of reaction components, not the mechanism or
how much time is needed for the chemical change to
take place (the rate).
 It predicts if a process is possible
 The goal of bioenergetics is to describe how living
organisms acquire and transform energy in order to
perform biological work.
 The reactions are classified as exergonic (energy
releasing) and endergonic (energy consuming)

5.  Biological energy transformations obey the Laws of
Thermodynamics.
 [Note : Thermodynamics is concerned with the flow of heat
and it deals with the relationship between heat and work.]
 First Law ofThermodynamics
 The total energy of a system, including its surroundings,
remains constant.
 This is also called the law of conservation of energy.
 Second Law ofThermodynamics
 The total entropy of a system must increase if a process is
to occur spontaneously.

6. GIBB’S FREE ENERGY(G)
 Gibbs free energy (G) expresses the amount of an energy
capable of doing work during a reaction at constant
temperature and pressure.
 The direction and extent to which a chemical reaction
proceeds is determined by the degree to which two factors
(enthalpy and entropy) change during the reaction.

7.  Enthalpy (H) is the heat content of the reacting system.
 It reflects the number and kinds of chemical bonds in the
reactants and products.
 When a chemical reaction releases heat, it is said to be
exothermic; the heat content of the products is less than
that of the reactants and ΔH has a negative value.
 Reacting systems that take up heat from their surroundings
are endothermic and have positive values of ΔH.
 Entropy (S) is a quantitative expression for the randomness
or disorder in a system
 When the products of a reaction are less complex and more
disordered than the reactants, the reaction is said to
proceed with a gain in entropy.

9.  The units of ∆G and ∆H are joules/mole or calories/mole
 Units of entropy are joules/mole x Kelvin (J/mol *K)
 Under the conditions existing in biological systems
(including constant temperature and pressure), changes
in free energy, enthalpy, and entropy are related to each
other quantitatively by the equation
∆G = ∆H -T ∆ S
 ∆G is the change in Gibbs free energy of the reacting
system
 ∆H is the change in enthalpy of the system
 T is the absolute temperature
 ∆S is the change in entropy of the system.
∆S has a positive sign when entropy increases and ∆H has a negative sign when
heat is released by the system to its surroundings.

10. •Relationship between changes in free energy (G), enthalpy (H), and entropy(S)
•T is the absolute temperature in Kelvin (K)

11.  The change in free energy is represented in two ways, ΔG and
ΔGo.
 ΔG represents the change in free energy and, thus, the
direction of a reaction at any specified concentration of
products and reactants. ΔG, then, is a variable.
 ΔGo is the energy change when reactants and products are at
a concentration of 1 mol/l. [Note: The concentration of
protons is assumed to be 10–7 mol/l (that is, pH = 7).
 Although ΔGo, a constant, represents energy changes at
these non physiologic concentrations of reactants and
products, it is nonetheless useful in comparing the energy
changes of different reactions.

12. (A)Sign of ΔG and the direction of a reaction:
 ΔG can be used to predict the direction of a reaction at
constant temperature and pressure.
 Negative ΔG: If ΔG is negative, there is a net loss of energy
and the reaction is said to be exergonic.
 Positive ΔG: If ΔG is positive, there is a net gain of energy,
and the reaction is said to be endergonic.
 ΔG is zero: If ΔG = 0, the reactants are in equilibrium. [Note:
When a reaction is proceeding spontaneously (that is, free
energy is being lost) then the reaction continues until ΔG
reaches zero and equilibrium is established.]

13. (B) ΔG of the forward and back reactions:
 The free energy of the forward reaction (A → B) is equal
in magnitude but opposite in sign to that of the back
reaction (B → A).
 For example, if ΔG of the forward reaction is −5 kcal/mol,
then that of the back reaction is +5 kcal/mol.
(C) ΔG and the concentration of reactants and products:
 The ΔG of the reaction A → B depends on the
concentration of the reactant and product.
 At constant temperature and pressure,
ΔG = ΔG0 +RT ln [B]
[A]

14.  where ,
 ΔGo is the standard free energy change
 R is the gas constant (1.987 cal/mol K)
 T is the absolute temperature (K)
 [A] and [B] are the actual concentrations of the reactant
and product
 ln represents the natural logarithm.
 A reaction with a positive ΔGo can proceed in the forward
direction (have a negative overall ΔG) if the ratio of
products to reactants ([B]/[A]) is sufficiently small (that is,
the ratio of reactants to products is large).

15.  For example, consider the reaction:
 Concentration of Glucose 6-phosphate, is high compared
with the concentration of product, fructose 6-
phosphate.
 This means that the ratio of the product to reactant is
small, and RT ln([fructose 6-phosphate]/[glucose 6-
phosphate]) is large and negative, causing ΔG to be
negative despite ΔGo being positive.
 Thus, the reaction can proceed in the forward direction.

16. (D) Standard free energy change
 Τhe standard free energy change, ΔGo, is the free energy
change, ΔG, under standard conditions (ie, when reactants
and products are at 1 mol/l concentrations or at PH 7).
 Under these conditions, the natural logarithm of the ratio
of products to reactants is zero (ln1 = 0), and, therefore,
the equation becomes:
ΔG = ΔGo + 0
(i) ΔGo and the direction of a reaction:
 Under standard conditions, ΔGo can be used to predict the
direction a reaction proceeds because, under these
conditions, ΔGo = ΔG.
 However, ΔGo cannot predict the direction of a reaction
under physiologic conditions, because it is composed
solely of constants (R, T, and Keq and is not, therefore,
altered by changes in product or substrate concentrations.

17. (ii) Relationship between ΔGo and Keq (equilibrium constant)
 In a reaction A B, a point of equilibrium is reached at
which no further net chemical change takes place (that is,
when A is being converted to B as fast as B is being
converted to A).
 In this state, the ratio of [B] to [A] is constant, regardless of
the actual concentrations of the two compounds:
 where Keq is the equilibrium constant, and [A]eq and [B]eq
are the concentrations ofA and B at equilibrium.
 If the reaction A B is allowed to go to equilibrium at
constant temperature and pressure, then, at equilibrium, the
overall ΔG is zero.
 Therefore,

18.  where the actual concentrations of A and B are equal to
the equilibrium concentrations of reactant and product
[A]eq and [B]eq, and their ratio is equal to the Keq.
 Thus,
 This equation allows some simple predictions:
(iii) ΔGo of two consecutive reactions:
 The ΔG0 s are additive in any sequence of consecutive
reactions, as are the ΔG-s.
 For eg:

19. (iv) ΔGs of a pathway:
 The additive property of free energy changes is very
important in biochemical pathways through which
substrates must pass in a particular direction(A B C….)
 As long as the sum of the ΔGs of the individual reactions is
negative, the pathway can potentially proceed, even if
some of the individual reactions of the pathway have a
positive ΔG.
 The actual rate of the reactions depend on the lowering of
activation energies by the enzymes that catalyze the
reactions

20. Redox potential
 Redox potential or oxidation reduction potential is a
quantitative measure of the tendency of a redox pair to lose
or gain electrons (ie. It is the electron transfer potential of a
system).
 The redox pairs are assigned specific standard redox
potential (E0 volts) at PH 7 and at 25°C
 Oxidation is the loss of electrons and reduction is the gain of
electrons.
 When a substance exists both in the reduced state and in
the oxidized state, the pair is called a redox couple.

21.  The flow of electrons in oxidation-reduction reactions is
responsible, directly or indirectly, for all work done by living
organisms
 Electrons are transferred from one molecule (electron
donor) to another (electron acceptor) in one of four ways:
1. Directly as electrons.
2. As hydrogen atoms.
3. As a hydride ion (:H-), which has two electrons.
4. Through direct combination with oxygen.
 The redox potential of this couple is estimated by
measuring the electromotive force (EMF) of a sample half
cell connected to a standard half cell.

22.  The sample half cell contains one molar solution each of
the reductant and oxidant.
 The reference standard half cell has 1 M H+ solution in
equilibrium with hydrogen gas at one atmosphere
pressure.
 The reference half cell has a reduction potential of zero
meV.
 When a substance has lower affinity for electrons than
hydrogen, it has a negative redox potential.
 If the substance has a higher affinity for electrons than
hydrogen, it has a positive redox potential.

23. Measurement of the standard reduction potential of a redox pair.

24.  Standard reduction potential can be used to calculate free
energy change.
 Electrons tend to flow to the half-cell with the more positive
reduction potential, and the strength of that tendency is
proportional to ∆E, the difference in reduction potential.
 The energy made available by this spontaneous electron
flow (the free-energy change, ∆G, for the oxidation-
reduction reaction) is proportional to ∆E:
∆G0 = -n F ∆Eo.
 where
 n is the no: of electrons transferred in the reaction.
 F = Faraday constant (23.1 kcal/volt mol)
 ΔEo = Eo of the electron-accepting pair minus the Eo of the
electron-donating pair
 ΔGo = change in the standard free energy

25. The redox potentials of some of the important redox couples of
the biological system.

26. ENERGYRICHCOMPOUNDS
 Certain compounds in the biological system on
hydrolysis yield energy.
 High energy compounds or energy rich compounds are
those substances which possess sufficient free energy to
liberate at least 7 Cal/mol at pH 7.0
 The compounds that liberate less than 7 Cal/mol are
known as low energy compounds.
 Most of the high energy compounds contain phosphate
group and hence they are known as the high energy
phosphate compounds

27. Compounds ∆G0 (Cal/mol)
High energy phosphate
Phosphoenol pyruvate -14.8
Carbamoyl phosphate -12.3
Cyclic AMP -12.0
1,3-Bisphosphoglycerate -11.8
Phosphocreatine -10.3
Acetyl phosphate -10.3
S-Adenosylmethionine -10.0
Pyrophosphate -8.0
AcetylCoA -7.7
ATP ADP+Pi -7.3
Low energy phosphates
ADP AMP + Pi -6.6
Glucose-1-phosphate -5.0
Fructose-6-phosphate -3.8
Glucose-6-phosphate -3.3
Glycerol-3-phosphate -2.2

28. CLASSIFICATIONOFHIGHENERGYCOMPOUNDS
 There are at least 5 groups of high energy compounds
1. Pyrophosphates
2. Acylphosphates
3. Enol phosphates
4. Thioesters
5. Phosphagens

30. HIGHENERGYBONDS
 The high energy compounds possess acid anhydride
bonds (mostly phosphoanhydride bonds ) which are
formed by the condensation of two acidic groups or
related compounds.
 These bonds are called high energy bonds since the free
energy is liberated when these bonds are hydrolysed.
 The symbol ~ is used to represent high energy bonds
 Eg: ATP ~ P ~ P

31. ATP
 ATP is the most important high energy compound in the living
cells.
 It consists of an adenine, a ribose & a triphosphate moiety.
 ATP is a high-energy compound due to the presence of two
phosphoanhydride bonds in the triphosphate unit.
 ATP serves as the energy currency of the cell.

32. BIOLOGICAL SIGNIFICANCE:
 The hydrolysis of ATP is associated with the release of large
amount of energy.
ATP + H2O ADP + Pi + 7.3 Cal
 The energy liberated is used for various processes like muscle
contraction, active transport etc.
 ATP can act as a donor of high-energy phosphate to low-
energy compounds, to make them energy rich.
 ADP can accept high-energy phosphate from the compounds
possessing higher free energy content to formATP.
 ATP is constantly being utilized and regenerated.
 This is represented by ATP-ADP cycle, the fundamental basis
of energy exchange reactions in living system.
 ATP acts as an energy link between the catabolism
(degradation of molecules) and anabolism( synthesis) in the
biological system.

33. SYNTHESIS OF ATP:
 ATP can be synthesized in two ways:
1. Oxidative phosphorylation :
 This is the major source of ATP in aerobic organisms
 lt is linked with the mitochondrial electron transport chain .
2. Substrate level phosphorylation :
 ATP may be directly synthesized during substrate oxidation in
the metabolism.
 The high-energy compounds such as phospho enolpyruvate
and 1,3-bisphosphoglycerate and succinyl CoA can transfer
high-energy phosphate to ultimately produceATP.

35. CYCLICAMP
 cAMP is a cyclic nucleotide.
 Chemically it is 3΄5΄ adenosine monophosphate.
 It is synthesized in tissues from ATP under the influence of
adenylyl cyclase in presence of Mg ions.
 cAMP decomposition into AMP is catalyzed by the enzyme
phosphodiesterase.
 cAMP is a second messenger.
 It is used for intracellular signal transduction, such as
transferring the effects of hormones like glucagon and
adrenaline, which cannot pass through the cell membrane.
second messengers are short lived intracellular signaling molecules released by the cell to
trigger physiological changes such as proliferation, differentiation, migration, survival and
apoptosis

36.  cAMP is involved in the activation of protein kinases and
regulates the effects of adrenaline and glucagon.
 cAMP also regulates the passage of Ca2+ through ion channels.
 cAMP and its associated kinases function in several
biochemical processes including the regulation of glycogen,
sugar and lipid metabolism by activating protein kinase.
cAMP is a mediator of hormone action
Activates protein kinase A
Causes glycogenolysis
Causes lipolysis.
Modulates transcription
Activates hormone secretion
Increases gastric secretion.
Regulates cell permeability to water