Biochem-706

2(2-0)

BIOENERGETICS
 Marks Sessional Mid Final Total

Criteria Assignments Paper Paper

Theory
Assessment
4 (10%) 12 24 40
(100%)
Result
Total: 40 Marks
CONTENTS

Principles of cell bioenergetics, thermodynamics and biological energy

transformation, hydrolysis of phosphorylated compounds, thioesters and group
transfer. Oxidation-reduction reactions: classification of redox enzymes;
oxidases, aerobic dehydrogenases, anaerobic dehydrogenases, peroxidases,
oxygenases. Standard redox potentials, Electron-transfer reactions in
mitochondria, complexes of the respiratory chain and their sequence, free and
membrane bound carriers, shuttle systems for indirect oxidation of cytosolic
NADH in mitochondria. Respiratory chain inhibitors. Photophosphorylation;
noncyclic and cyclic electron flow. Mechanism of ATP synthesis;
Chemiosmotic Model, structural organization of ATP synthase and mechanism
of oxidative phosphorylation, rotational catalysis and Binding-Change
Mechanism, proton pumps, proton motive force and active transport of
protons. Regulation of oxidative phosphorylation.
Suggested Readings

• Ferrier, D. R. 2013. Biochemistry: Lippincott's Illustrated Reviews. 6th ed.

Lippincott Williams and Wilkins. U.S.A.

• Murray, R.K., D.A. Bender, K. M. Botham, P.J. Kennelly, V.W. Rodwell

and P.A.Weil. 2012. Harper’s Illustrated Biochemistry. 29th ed. McGraw
Hill. New York, NY, USA.

• Nelson, D.L and M.M. Cox. 2013. Lehninger Principles of Biochemistry.

6th ed. Worth Publishers, New York, NY, USA.

• Voet, D., J. G. Voet and C.W. Pratt. 2013. Fundamentals of Biochemistry,

Life at the Molecular Level. 4th ed. John Wiley & Sons. Inc. New York,
NY, USA.
• Living cells, organisms must perform work - to stay alive, to grow, & to reproduce

• Fundamental property of living organisms –

1. Ability to harness (produce) energy
2. To channel it into biological work

• Organisms carry out a remarkable variety of energy transductions

• Conversions of one form of energy to another

• Use chemical energy in fuels to bring about synthesis of complex, highly ordered
macromolecules from simple precursors

• Convert chemical energy of fuels into concentration gradients & electrical

gradients, into motion, heat, light (fireflies, deep-sea fish)

• Photosynthetic organisms transduce light energy into all these other forms of
energy
• Energy Transduction:
The action or process of converting something and especially energy or a
message into another form
OR
In biophysics, transduction is the conveyance of energy from one electron (a
donor) to another (a receptor), at the same time that the class
of energy changes

Definition - Bioenergetics
The quantitative study of energy transductions
1. Changes of one form of energy into another
2. Nature & function of chemical processes underlying these
transductions
 Biological Energy Transformations Obey Laws of Thermodynamics
• Two fundamental laws of thermodynamics

First law of thermodynamics (principle of conservation of energy)

“For any physical or chemical change, total amount of energy in universe

remains constant; energy may change form or it may be transported from one
region to another, but it cannot be created or destroyed”

Second law of thermodynamics

(Universe always tends toward increasing disorder: in all natural processes,
entropy of universe increases)

“In all natural processes, entropy of the universe increases”

THERMODYNAMICS: Branch of physical science that deals with relations between heat & other forms
of energy (such as mechanical, electrical, or chemical energy), and, by extension, of relationships
between all forms of energy
Characteristics of living organisms
1. Collections of molecules
2. Much more highly organized than surrounding materials from which they
are constructed
3. Maintain & produce order (seemingly immune to second law of
thermodynamics)

• BUT living organisms do not violate second law

• They operate strictly within it

• Reacting system: collection of matter that is undergoing a particular

chemical or physical process

• It may be an organism, a cell, or two reacting compounds

• Reacting system + its surroundings = the universe

• Closed system: Laboratory (chemical/physical processes conducted
without any exchange of material or energy with surroundings

• Open system: Living cells/organisms - exchange material & energy with

surroundings

• Living systems never at equilibrium with their surroundings

• Constant transactions between system & surroundings

• This transduction explain how organisms can create order within

themselves while operating within 2nd law of thermodynamics
 3 thermodynamic quantities that describe energy changes
occurring in a chemical reaction
1. Gibbs free energy, (G)
• Amount of an energy capable of doing work during a reaction at constant
temperature and pressure

• When a reaction proceeds with release of free energy (that is, when the
system changes so as to possess less free energy), free-energy change, ΔG,
has a negative value

• Reaction is said to be exergonic

• Endergonic reactions, system gains Free energy and ΔG is positive

2. Enthalpy, (H) is heat content of reacting system
• It reflects number & kinds of chemical bonds in reactants & products

• When a chemical reaction releases heat – called exothermic

• Heat content of products is < than that of reactants - ΔH is negative value

• Reacting systems that take up heat from their surroundings - endothermic

• ΔH is positive value

3. Entropy, S, is a quantitative expression for randomness or disorder in a

system

• When products of a reaction are less complex & more disordered than
reactants, the reaction is said to proceed with a gain in entropy
Units
• Δ G & Δ H - joules/mole or calories/mole (1 cal = 4.184 J)
• Entropy - joules/ mole.Kelvin (J/mol?K)
• Under conditions of biological systems (including constant temperature &
pressure), changes in free energy, enthalpy, & entropy are related to each other
quantitatively by equation
ΔG = Δ H - T Δ S
Δ G: change in Gibbs free energy of reacting system
ΔH: change in enthalpy of system
T: absolute temperature
ΔS: change in entropy of system

• By convention, ΔS - a positive sign when entropy increases

• ΔH - a negative sign when heat is released by system to its surroundings

• Either of these conditions, which are typical of energetically favorable processes,

tend to make ΔG negative

• In fact, ΔG of a spontaneously reacting system is always negative

• 2nd law of thermodynamics -entropy of universe increases during all chemical &
physical processes

• BUT, it does not require that entropy increase take place in reacting system itself

• Order produced within cells as they grow & divide is more than compensated for by
disorder they create in their surroundings in course of growth & division

• Summary: Living organisms preserve their internal order by taking from

surroundings free energy in form of nutrients or sunlight, & returning to
their surroundings an equal amount of energy as heat & entropy

Cells Require Sources of Free Energy

• Cells - isothermal systems

• Cells function at essentially constant temperature & pressure

• Heat flow is not a source of energy for cells, because heat can do work only as it
passes to a zone or object at a lower temperature
• Energy that cells can & must use is free energy, described by Gibbs free energy
function G

• G allows prediction of
1. Direction of chemical reactions,
2. their exact equilibrium position,
3. amount of work they can (in theory) perform (constant temperature, pressure)

4. Heterotrophic cells acquire free energy from nutrient molecules

5. Photosynthetic cells acquire it from absorbed solar radiation

6. Both kinds of cells transform this free energy into ATP & other energy-rich
compounds capable of providing energy for biological work at constant temperature
 Standard Free-Energy Change Is Directly Related to Equilibrium Constant

• Composition of a reacting system (mixture of chemical reactants & products) tends

to continue changing until equilibrium is reached

• At equilibrium:

1. concentration of reactants & products are equal

2. rates of forward & reverse reactions are equal

3. no further net change occurs in system

• Concentrations of reactants & products at equilibrium define equilibrium constant,

Keq
• In general reaction
aA +bB cC + dD

where a, b, c, d: number of molecules of A, B, C, D participating

• Equilibrium constant is given as:

where [A], [B], [C], [D]: molar concentrations of reaction components at

equilibrium

• When a reacting system is not at equilibrium, tendency to move toward

equilibrium represents a driving force, magnitude of which can be
expressed as the free-energy change for the reaction, ΔG
• Under standard conditions (298 K = 25oC), when reactants & products are initially
present at 1 M concentrations or, for gases, at partial pressures of 101.3 kilopascals
(kPa), or 1 atm, force driving system toward equilibrium is defined as standard free-
energy change, Δ G

• By this definition, standard state for reactions that involve hydrogen ions is [H] =
1M or pH 0

• Most biochemical reactions, however, occur in well-buffered aqueous solutions

near pH 7; both pH & concentration of water (55.5 M) are essentially constant

KEY CONVENTION:
• For convenience of calculations, biochemists define a standard state different from
that used in chemistry and physics: in biochemical standard state, [H+] = 10-7 M (pH
7) & [H2O] is 55.5 M

• For reactions that involve Mg (which include most of those with ATP as a reactant),
[Mg2+] in solution is commonly taken to be constant at 1 mM
• Physical constants based on this biochemical standard state are called standard
transformed constants & are written with a prime (such as ΔG΄ο , ΔKeq΄)

• Prime distinguish them from the untransformed constants used by chemists &
physicists

• For simplicity transformed constants are described as standard free-energy changes

• Simple relation between ΔG΄ο & ΔKeq΄

• Standard free-energy change of a chemical reaction is simply an alternative

mathematical way of expressing its equilibrium constant
• Table 13-2 shows the relationship between ΔG΄ο and K΄eq

• If equilibrium constant for a given chemical reaction is 1.0, standard free-energy

change of that reaction is 0.0 (natural logarithm of 1.0 is zero)

• If K΄eq of a reaction is greater than 1.0, its ΔG΄ο is negative

• If K΄eq is less than 1.0, ΔG΄ο is positive

• Because relationship between ΔG΄ο & K΄eq is exponential, relatively small changes
in ΔG΄ο correspond to large changes in K΄eq
• ΔG΄ο is difference between free-energy content of products & free-energy content
of reactants, under standard conditions

• When ΔG΄ο - negative, products contain less free energy than reactants

• Reaction will proceed spontaneously under standard conditions

• All chemical reactions tend to go in direction that results in a decrease in free

energy of system

• A positive value of ΔG΄ο - products of reaction contain more free energy than
reactants

• Reaction will tend to go in reverse direction if we start with 1.0 M concentrations of

all components (standard conditions) Table 13–3
 Standard Free-Energy Changes Are Additive
• Sequential chemical reactions:
A↔B and B↔C
• Each reaction has own
1. equilibrium constant
2. standard free-energy change ΔG1΄ο, ΔG2΄ο

• For sequential reaction: B cancels out to give overall reaction

A↔C
• This reaction also has its own equilibrium constant & standard free-energy
change ΔGTotal΄ο

• ΔG΄ο values of sequential chemical reactions are additive

• For overall reaction A ↔ C

• ΔGTotal΄ο is sum of individual standard free-energy changes ΔG1΄ο &
ΔG2΄ο
• ΔGTotal΄ο = ΔG1΄ο + ΔG2΄ο

• Principle of bioenergetics
• Explains how a thermodynamically unfavorable (endergonic) reaction can
be driven in forward direction by coupling it to a highly exergonic reaction
through a common intermediate
EXAMPLE
Synthesis of glucose 6-phosphate is first step in utilization of glucose by many
organisms

• Positive value of ΔG΄ο predicts that under standard conditions reaction will
tend not to proceed spontaneously in direction written
• Another cellular reaction, the hydrolysis of ATP to ADP and Pi, is very
exergonic:

• Both reactions share common intermediates Pi & H2O and may be

expressed as sequential reactions:

• Overall standard free-energy change is obtained by adding values for

individual reactions:
• Overall reaction – exergonic

• Energy stored in ATP is used to drive the synthesis of glucose-6-phosphate

• Even though its formation from glucose & inorganic phosphate (Pi) is
endergonic

• Pathway of glucose 6-phosphate formation from glucose by phosphoryl

transfer from ATP is different from reactions (1) and (2) above

• But net result is same as sum of two reactions

• In thermodynamic calculations, all that matters is state of

system at beginning of process & its state at end; route
between initial and final states is immaterial (unimportant, irrelevant)
• We have said that ΔG΄ο is a way of expressing equilibrium constant for a
reaction
• For reaction (1),

• For reaction (2),

• Equilibrium constant for 2 coupled reactions:

• This calculation illustrates an important point about equilibrium constants:

• Although ΔG΄ο values for two reactions sum to a third value

• Overall reaction are additive

• Keq for overall reaction is product of individual Keq values for 2 reactions

• Equilibrium constants are multiplicative

• By coupling ATP hydrolysis to glucose 6-phosphate synthesis, Keq for

formation of glucose 6-phosphate from glucose has been raised by a factor
of about 2 x 105

• This is a common-intermediate strategy

• Employed by all living cells in synthesis of metabolic intermediates & cellular

components

• Obviously, strategy works only if compounds such as ATP are continuously

available