Department of chemistry

GFGC. Chickballapur
BIOENERGETICS & BIOLOGICAL OXIDATION

All living organisms require energy for different activities like motion, transport across
membrane barriers, synthesis of biomolecules, information transfer, maintain body
temperature etc. The energy comes from sun (light energy) which is converted to
chemical energy. Living organisms can change energy from one form to another. The
branch of chemistry which deals with the use and transformation of energy by living
organisms is called bioenergetics.

The major stages of biological energy transformation

The flow of energy through living organisms takes by 3 steps.

1. Photosynthesis- conversion of solar energy into chemical bond energy

6CO2 + 6H2O C6H12O6 + O2

2. Cellular respiration- oxidation of food to generate ATP

C6H12O6 + O2 6CO2 + 6H2O +ATP

3. Utilisation of ATP

Living organisms and thermodynamics

The most important and universal form of energy is heat. This is simplest medium by
which energy may be transformed. However it is not the medium to transform in
biological systems because living organisms are isothermal and there is no temperature
difference between different parts of a cell. Under isothermal conditions free energy is
the useful medium of energy transformation.

Free energy is that portion of energy that is available to do work under isothermal
conditions. Living organisms derive energy from food stuff and denoted by G. it is the
most useful criteria for predicting spontaneity or feasibility of a process.
The change in free energy ΔG of a reaction depends on the change in enthalpy ΔH (sum
of bond energies), the change in entropy ΔS (the randomness of molecular motion), and
the temperature. The change in free energy ΔG is the most useful measure for
predicting the direction of chemical reactions in biological systems.

ΔG= ΔH − T ΔS

The sign and magnitude of ΔG helps to predict the spontaneity of a reaction.

 If ΔG is positive, the reaction is non spontaneous and input of energy for the reaction to
occur. Such reactions are called endergonic reactions.

If ΔG is negative, the reaction is spontaneous and energy is liberated. Such reactions

are called exergonic reactions.

Exergonic and endergonic reactions

An exergonic reaction is one in which free energy is released and ΔG is negative and the
reaction proceeds spontaneously.

ATP + H2O ADP + Pi ΔG0 = -7.3 Kcal/moll

ADP + H2O AMP + Pi ΔG0 = -7.3 Kcal/mol

PPi 2 Pi ΔG0 = -8.0 Kcal/mol

Pyrophosphate

Endergonic reaction

An endergonic reaction is one in which free energy is absorbed and ΔG is positive and
the reaction cannot proceed spontaneously.

ADP + Pi ATP + H2 O ΔG0 = +7.3 Kcal/mol

AMP + Pi ADP + H2O ΔG0 = +7.3 Kcal/mol

2 Pi PPi ΔG0 = -8.0 Kcal/mol

If a reaction is exergonic in one direction, it is endergonic in opposite direction.

Energy coupling

Living cells require energy for many processes. In many cases substances must be
activated before they can release energy contained in them. This requires energy which
is obtained by the coupling of exergonic reactions with endergonic reaction. This is
called energy coupling.
In energy coupling free energy in thermodynamically favourable exergonic reaction is
used to drive thermodynamically unfavourable endergonic reactions. An exergonic
reaction and endergonic reactions are coupled by the common intermediate. So that the
overall free energy change for the coupled reaction is negative. Usually ATP acts as a
common intermediate between coupled reactions.

1. Glucose + Pi Glucose -6- phosphate + H2O ΔG0 = +3.3 Kcal/mol

ATP+ H2O ADP + H2O ΔG0 = -7.3 Kcal/mol

Glucose + ATP Glucose-6- phosphate +ADP ΔG0 = -4.0 Kcal/mol

2. Phosphoenol pyruvate pyruvate +Pi ΔG0 = -14.8 Kcal/mol

ADP + Pi ATP + H2O ΔG0 = +7.3 Kcal/mol

Phosphoenol pyruvate + ADP Pyruvate +ATP ΔG0 = -7.5 Kcal/mol

High energy compounds or energy rich compounds

Energy can be stored in the chemical bonds within molecules. When these bonds are
broken, large amount of energy will be released. Molecules containing high-energy
bonds are called energy-rich compounds. These energy-rich compounds are the cell’s
currency — they can be used to power energy-consuming biochemical reactions.

Many biochemical reactions are thermodynamically unfavourable. So one of the

biomolecules mediate the flow of energy from exergonic to endergonic reactions or
energy requiring processes. ATP is the common coupling intermediate molecule which
mediates many biochemical reactions.

Cells contain other high energy compounds with std. free energy values more than ATP.
Such compounds are called super high energy compounds.

The following table gives some high energy compounds other than ATP.
ADENOSINE TRIPHOSPHATE

The ATP molecule is composed of three components. Ribose, sugar, adenine base and
three phosphate groups.

1. ATP serves as a high-energy compound.

The three phosphate groups are linked to one another by two high-
energy bonds called phosphoanhydride bonds which are referred as
high-energy bonds. The phosphoanhydride bond has a high free energy change
on hydrolysis.
2. The ∆Go for hydrolysis of ATP is –30 kJ/mol. (-7.3 kcal/mol) which is more
negative than most biochemical reactions than hydrolysis of phosphorylated
compounds such as Glc-6-PO4 or Glycerol-3-PO4. This means that ATP has a
higher phosphoryl transfer potential than these compounds.
3. The products of ATP hydrolysis, ADP and Pi are much more stable than ATP.
Factors that make ADP + Pi more stable than ATP:
4. Phosphate groups are negatively charged and thus repel one another when they
are arranged in series, as they are in ADP and ATP. This repulsion makes the
ADP and ATP molecules unstable. The hydrolysis relieves the electron-electron
repulsions experienced by the negatively charged phosphate groups.

BIOLOGICAL OXIDATION

An oxidation-reduction (redox) reaction is a type of chemical reaction that involves a

transfer of electrons between two atoms or compounds. The substance that loses
the electrons is said to be oxidized, while the substance that gains the electrons is
said to be reduced. Redox reactions always have to occur together. If one molecule
is oxidized, then another molecule has to be reduced.
Redox reactions occurring in biological systems are known as biological oxidation.
Redox reactions contains 2 half reactions i.e. reduction half and the oxidation half.
In biological systems redox reactions are common and they form the basis of
bioenergetics.

Fe2

Comparison of biological oxidation with combustion

Combustion is the complete oxidation of organic compound into carbon dioxide
and water molecules in presence of oxygen gas whereas oxidation is the addition of
oxygen in a compound or addition with an element. Combustion reactions involve
heat and light whereas oxidation reaction does not involve heat.
When one molecule of glucose undergoes combustion in a single step, the change in
free energy is -686k cal /mol. If this energy is released in a one step in biological
systems which cannot be conserved efficiently, because only one ATP can be
synthesized per step.

C6H12O6 + O2 6CO2 + 6H2O ΔG0 = +7.3 Kcal/mol

But in biological systems glucose is oxidized in many steps which enable
the control of energy input and energy output at each step and energy
released can be conserved much more efficiently than in combustion.
Only a part of energy appears as heat and remaining is converted to
chemical energy i.e. ATP.
Totally 38 ATPs are obtained from each glucose oxidation.
Free energy content of 1ATP - -7.3k cal/mol
Free energy content of 38 ATP - -7.3 x 38 = -277.4k cal/mol

ΔG0 corresponding to 38 ATP Molecules x100

ΔG0 corresponding to 1 ATP Molecules

= 277.4 x100 =40%

686

Electron transport chain

It is the final metabolic pathway in which electrons derived from various fuel
molecules are transferred to oxygen. In aerobic organisms glucose and fatty acids
are oxidized to CO2 and H2O with the release of electrons which are transferred to
electron carriers or co enzymes like NAD and FAD. NAD and FAD get reduced to
NADH and FADH2 which are high energy molecules. They donate a pair of
electrons to oxygen and large amount of energy will be released at one time and
wasted as heat. Hence aerobic organisms use a special mechanism to ensure that
energy is released in steps so that energy is conserved. Electrons from NADH and
FADH2 are transferred to oxygen through a specialized set of electron carriers
called electron transport chain. These carriers are arranged in the sequence of
decreasing redox potential. (Tendency of a molecule to donate or to accept electrons
is called redox potential). Energy released at each step is directly proportional to
the difference in the redox potential of 2 consecutive systems operating in that step.
Part of the energy is conserved as ATP.

In the ETC electron carriers are arranged such that electrons accepted from
NADH and FADH2flow in the direction of increasing redox potential to oxygen.
As the electrons move from NADH to FADH2 through electron carriers there will
be release of energy which is used to convert ADP to ATP. Since ATP is synthesized
in this way require oxygen and it is called oxidative phosphorylation.
The components of ETC are organized into 4 complexes which are embedded in
the inner mitochondrial membrane.
In Krebs cycle and glycolysis many intermediates undergo oxidation and electrons
are transferred to NAD and FAD which gets reduced to NADH and FADH2. These
reduced coenzymes donate electrons in the ETC.

Complex I
NADH dehydrogenase complex- As the name only indicates it carries out the
dehydrogenation of NADH and removes hydrogen and transfer into complex II. It
also contains FMN and Fe-S clusters. The first is the transfer of electrons from
NADH to FMN. Flavo proteins accept 2 electrons and get reduced to FMNH2.
FMNH2 is reoxidised and then passes one electron at a time to Coen Q which is
converted too CoenH2.

Complex-II
Succinate dehydrogenase complex- It contains prosthetic group FAD. It accepts
electrons from substrate and gets converted to FADH2. FADH2 then reoxidised by
donating electrons to Coen Q. Coen Q receives electrons from both Complex I and
II. It contains the Fe-S clusters.

Complex-III
Cytochrome bc1 complex- it contains cytochrome b and c1. Cytochrome is group of
proteins which has heme as prosthetic group and Fe core. The Fe will be in Fe2+ or
Fe3+state depending on the electrons.it accepts electrons from C-II and transfers
into C-IV

Complex-IV
Cytochrome oxidase- it transfers electrons from cytochrome-C to oxygen. It
contains 2 cytochromes a and a3.

Substrate NADH FMN Co-Q Cyto-bc1 Cyt-C Cyt- aa3

FAD

Substrate

Schematic diagram of electron transport chain

 The P/O ratio is the number of ATPs produced per pair of electrons travelling
through the ETC. depending on the point at which electrons enter the chain, the p/o
ratio will change. Electrons entering from NADH produce 3 ATPs per pair of
electrons. From FADH2 produces 2ATPs per pair of electrons.

Oxidative Phosphorylation

The products NADH and FADH2 formed during glycolysis and Krebs cycle are able to
reduce molecular oxygen thereby releasing large amount of energy to make ATP. The
process by which electrons are transferred from NADH or FADH2 to Q2 by a series of
electron carriers is known as oxidative phosphorylation.

Differences between oxidative and substrate level phosphorylation

Oxidative phosphorylation Substrate level phosphorylation

ADP and Pi are converted to ATP ADP and Pi are converted to ATP
using the energy released in the using the energy released by the
ETC by transfer of electrons hydrolysis of high energy
from high energy reduced
coenzymes.
Requires oxygen as final electrons
acceptor
Takes place in the mitochondrial
membrane
Carried out by ATP synthetase
compounds
Does not require oxygen
Takes place in the cytoplasm or
mitochondrial matrix
Carried out by various kinase
enzymes