BIOLOGICAL

OXIDATION
.
Bioenergetics predicts if A
process is possible, whereas
kinetics measures how fast the
reaction occurs
 LAWS OF THERMODYNAMICS
 FIRST LAW - “The total energy of a system
plus its surroundings remain constant”

 SECOND LAW – “ The total entropy of a

system must increase if a process is to
occur spontaneously”
 Under conditions of
constant temp. &
pressure, the
relationship between
free energy
change(ΔG) of a
reacting system & the
change in entropy(ΔS)
is expressed by the
equation:-----
FREE ENERGY
(ΔG )
 ΔG is that portion of total
energy change in a
system that is available
for executing a task, i.e. it
is the actual useful
amount of energy, also
known as CHEMICAL
POTENTIAL.
 If ΔG is –ve, Exergonic.
 If ΔG is +ve, Endergonic.
 If ΔG is zero, Equilibrium,
no net change.
 Free Energy Change
 The change in free energy comes in two forms, ΔG and ΔGo.
 The first, ΔG (without the superscript “o”), is the more
general because it predicts the change in free energy and,
thus, the direction of a reaction at any specified
concentration of products and reactants.
 This contrasts with the change in standard free energy, ΔGo
(with the superscript “o”), which is the energy change when
reactants and products are at a concentration of 1 mol/L.
 The concentration of protons is assumed to be 10 -7mol/L,
pH = 7.
 Although ΔGo represents energy changes at these non
physiologic concentrations of reactants and products, it is
useful in comparing the energy changes of different
reactions.
 ΔGo can readily be determined from measurement of the
equilibrium constant .
ΔG depends on 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, the following relationship
can be derived:

R=gas constant (1.987 cal/mole)

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).
 R=gas constant (1.987 cal/mole)
 For example, consider the reaction

 Reaction shows conditions in which the

concentration of reactant, 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
ΔGobeing positive.
 Thus, the reaction can proceed in the forward
direction.
Standard free energy change, ΔGo

 The standard free energy change, ΔGo, is so

called because it is equal to the free energy
change, ΔG, under standard conditions—
that is, when reactants and products are
kept at 1 mol/L concentrations.
 Under these conditions, the natural
logarithm (ln) of the ratio of products to
reactants is zero (ln 1 = 0) and, therefore,
the equation becomes:
ΔG = ΔGo + 0
ΔGo is predictive only under standard
conditions:
 Under standard conditions, ΔGo can be

used to predict the direction a reaction

proceeds because, under these conditions,
ΔGo is equal to 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, therefore, not altered
by changes in product or substrate
concentrations.
Relationship between ΔGo and Keq:
 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:

Keq is the equilibrium constant

[A]eq and [B]eq are the concentrations of A
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 free
energy change (ΔG) is zero. Therefore,

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 as shown
above is equal to the Keq. Thus,
This equation allows some simple
predictions:
ΔGo of two consecutive reactions
are additive
The standard free energy changes (ΔGo) are
additive in any sequence of consecutive
reactions, as are the free energy changes (ΔG).
For example
ΔGs of a pathway are additive:
 This additive property of free energy changes is
very important in biochemical pathways through
which substrates must pass in a particular
direction (for example, A → B → C → D → …).
 As long as the sum of the ΔGs of the individual
reactions is negative, the pathway can potentially
proceed as written, even if some of the individual
component reactions of the pathway have a
positive ΔG.
 The actual rate of the reactions does, of course,
depend on the activity of the enzymes that
catalyze the reactions
Mechanical model of
coupling of favourable
and unfavourable
processes
ENERGY IS CARRIED BY
ATP
High-Energy Phosphates Play a
Central Role in Energy Capture
and Transfer
ATP plays a central role in transference of free
energy from the exergonic to the endergonic
processes.

Adenosine
triphosphate (ATP)
shown as
magnesium
complex.

ADP also forms a

similar complex
with Mg2+
The standard free energy of
hydrolysis of biochemically
important phosphates
High-Energy
Phosphates Are
Designated by
 The symbol indicates that the
group attached to the bond, on
transfer to an appropriate
acceptor, results in transfer of
the larger quantity of free
energy.
 For this reason, the term group
transfer potential, rather than
"high-energy bond," is also in
use.
 Thus, ATP contains two high-
energy phosphate groups and
ADP contains one, whereas the
phosphate in AMP (adenosine
monophosphate) is of the low-
energy type, since it is a normal
ester link.
 Other High Energy Compounds
1) Acetyl CoA
2) Acyl carrier protein
3) Amino acid esters involved in protein
synthesis
4) S- adenosylmethionine
5) UDP – Glucose, UDP- Galactose
6) 5 –phosphoribosyl- 1 pyrophosphate
Role of ATP/ADP cycle in
transfer of high-energy
phosphate
ATP/ADP cycle
connects those
processes that generate
high energy Phosphate
to those processes that
utilize it, continuously
consuming and
regenerating ATP.

This occurs at a very

rapid rate, since the
total ATP/ADP pool is
extremely small and
sufficient to maintain an
active tissue for only a
few seconds
There are three major sources of
taking part in energy transfer

1) Oxidative phosphorylation
2) Glycolysis
3) The citric acid cycle
Phosphagens act as storage forms of
high-energy phosphate--- ( creatine
phosphate)

Transfer of high-energy phosphate

between ATP and creatine
When ATP acts as a phosphate donor to form those
compounds of lower free energy of hydrolysis , the
phosphate group is invariably converted to one of
low energy.
ATP Allows the Coupling of
Thermodynamically Unfavorable
Reactions to Favorable Ones

When (1) and (2) are coupled in a reaction catalyzed

by hexokinase, phosphorylation of glucose readily
proceeds in a highly exergonic reaction that under
physiologic conditions is irreversible.
 Adenylyl Kinase (Myokinase)
Interconverts Adenine Nucleotides
 This enzyme is present in most cells.
 It catalyzes the reaction

This allows:---
1. High-energy phosphate in ADP to be used in the synthesis
of ATP.
2. AMP, formed as a consequence of several activating
reactions involving ATP, to be recovered by
rephosphorylation to ADP.
3. AMP to increase in concentration when ATP becomes
depleted and act as a metabolic (allosteric) signal to
increase the rate of catabolic reactions, which in turn lead
to the generation of more ATP
When ATP Forms AMP, Inorganic
Pyrophosphate (PPi) Is Produced
 ATP can also be hydrolyzed directly to AMP, with the
release of PPi. This occurs, for e.g., in the activation
of long-chain fatty acids.

ΔG0' of –19.2 kJ/mol

A combination of the above reactions makes it

possible for phosphate to be recycled and the
adenine
Other Nucleoside Triphosphates also
Participate in the Transfer of High-Energy
Phosphate
 By means of the enzyme nucleoside
diphosphate kinase, UTP, GTP, and CTP can be
synthesized from their diphosphates, e. g., UDP
reacts with ATP to form UTP.

All of these triphosphates take part in

phosphorylations in the cell.
Specific Nucleoside Monophosphate
Kinases Catalyze The Formation Of
Nucleoside Diphosphates From The
Corresponding Monophosphates

Thus, adenylyl kinase is a specialized

monophosphate kinase
Electron Transport
Chain
Metabolic Breakdown Of Energy
Yielding Molecules
•The metabolic intermediates of these
reactions donate electrons to specific
coenzymes- (NAD+) and (FAD)—to form the
energy-rich reduced coenzymes, NADH and
FADH2.

• These reduced coenzymes can donate a

pair of electrons to a specialized set of
electron carriers, collectively called electron
transport chain.

•As electrons are passed down the electron

transport chain, they lose much of their free
energy. Part of this energy can be captured
and stored as ATP
This process is called oxidative phosphorylation
Electron transport and
ATP synthesis proceed
continuously in all
tissues.
 The inner mitochondrial
membrane is a specialized
structure that is impermeable
to most small ions, including
H+, Na+, and K+, and small
molecules such as ATP, ADP,
pyruvate, and other
metabolites important to
mitochondrial function

Mitochondria is the power

house of the cell.
 Electron Transport Chain

The reduced coenzymes NADH and FADH2 each donate a pair of

electrons to a specialized set of electron carriers, consisting of
FMN, coenzyme Q, and a series of cytochromes, collectively
called the electron transport chain.
Components of ETC
Q and cyt c are mobile components of the system as
indicated by the dotted arrows.
Many Dehydrogenases Depend
Upon Nicotinamide Coenzymes

 Both electrons but only one proton (e.g., a hydride

ion, :H-) are transferred to the NAD+, forming NADH
plus a free proton, H+.
•The free proton plus the hydride Iron-sulfur
ion carried by NADH are next
transferred to NADH
center
dehydrogenase, an enzyme
complex (Complex I) embedded in
the inner mitochondrial
membrane.
• This complex has a tightly bound
molecule of flavin
mononucleotide (FMN, a
coenzyme structurally related to
FAD, that accepts the two
hydrogen atoms (2e-+2H+),
becoming FMNH2.
•These are necessary for the
• NADH dehydrogenase also
transfer of the hydrogen
contains several iron atoms
atoms to the next member
paired with sulfur atoms to
of the chain, ubiquinone
make iron–sulfur centers .
(known as coenzyme Q).
Other Dehydrogenases Depend On
Riboflavin

Oxidoreduction of isoalloxazine ring in flavin nucleotides

via a semiquinone (free radical) intermediate
Fig. 25-5a, p. 923
Site-specific
inhibitors of
electron transport
 These compounds prevent the
passage of electrons by binding to a
component of the chain, blocking
the oxidation/reduction reaction.
 Therefore, all electron carriers
before the block are fully reduced,
whereas those located after the
block are oxidized
Electron transport and ATP
synthesis are tightly coupled
processes; therefore, inhibition of
the electron transport chain also
results in inhibition of ATP
synthesis
 Oxidation ( -e) of one
compound is always
accompanied by
reduction
( +e) of a second
•substance
Redox pairs differ in their
tendency to lose electrons.
•This tendency is a
characteristic of a particular
redox pair, and can be
quantitatively specified by a
constant, Eo
(the standard reduction
potential), with units in volts.

The components of the electron

transport chain are arranged in order
of increasingly positive E0 values.
•The standard reduction
potentials of various redox pairs
can be listed to range from the
most negative Eo to the most
positive.
•The more negative the
standard reduction potential of
a redox pair, the greater the
tendency of the reductant
member of that pair to lose
electrons.
• The more positive the Eo, the
greater the tendency of the
oxidant member of that pair to
accept electrons.
•Therefore, electrons flow from the
pair with the more negative Eo to
that with the more positive Eo
Redox Potentials Of
Mammalian Oxidation Systems.
P:O RATIO & EFFICIENCY OF ETC
 The standard free energy for the phosphorylation of
ADP to ATP is +7.3 kcal/mol. The transport of a pair
of electrons from NADH to oxygen via the electron
transport chain produces 52.58 kcal.
 Therefore, more than sufficient energy is available
to produce three ATP from three ADP and three Pi(3
× 7.3 = 21.9 kcal/mol), sometimes expressed as a
P:O ratio (ATP made per O atom reduced) of 3:1.
 The remaining calories are used for ancillary
reactions or released as heat.
 P:O for FADH2 is 2:1
 COMPLEX І (NADH -Ubiquinone oxidoreductase )

•Also called NADH- CoQ

reductase.
•Tightly bound to inner
mitochondrial membrane.
•Contains a flavoprotein
consisting of FMN as
prosthetic group & an Fe-
S protein.
•NADH FMN FeS
CoQ
•There is a large energy
4H+
released (12 Kcal/mol)
and 4 protons are
pumped
NADH + Co out .
Q(oxidized) → NAD+ + Co Q(reduced)
∆ G0= - 69.5
kj.mol-1
 COMPLEX ІІ (succinate -Ubiquinone
oxidoreductase )
•The electrons from
FADH2 enter the ETC at
the level of CoQ.

•This step does not

liberate enough energy
to act as proton pump.

•Substrates oxidised by
FAD-linked enzymes
bypass Complex- I.

FADH2 + CO Q(oxidized) → FAD + CO Q(reduced)

∆ G0= - 16.4 kj.mol-1
 COMPLEX ІІІ (Co Q – Cyt c oxidoreductase
)
This is a cluster of FeS
protein, cytochrome b
and cytochrome c.
During this process of
transfer of electron,
the iron in haem group
shuttels between Fe3+
and Fe2+ forms.
The free energy change
is -10KCal/mol and 4
protons are pumped
out.

Co Q(reduced) + 2 Cyt c(oxidized) → Co Q(oxidized) + 2 Cyt c

(reduced)

∆ G0= - 36.7 kj.mo

 QH
QH 2
2
 COMPLEX ІV (Cyt c Oxidase)
•It contains different
proteins, including
cytochrome a &
cytochrome a3.
•It is tightly bound to the
mitochondrial
membrane.
•Four electrons are
accepted from
cytochrome c & passed
on to molecular oxygen.
Two protons are
2 pumped out.+ ½ O2 → 2 Cyt c(oxidized) + H2O
Cyt c (reduced)
∆ G0= - 112 kj.mol-1
COMPLEX І
NADH + Co Q(oxidized) → NAD+ + Co Q(reduced)
∆ G0= - 69.5 kj.mol-1
COMPLEX ІІ
FADH2 + Co Q(oxidized) → FAD + Co Q(reduced)
∆ G0= - 16.4 kj.mol-1
COMPLEX ІІІ
Co Q(reduced) + 2 Cyt c(oxidized) → Co Q(oxidized) + 2 Cyt c

(reduced)
∆ G0= - 36.7 kj.mol-1
COMPLEX ІV
2 Cyt c (reduced) + ½ O2 → 2 Cyt c(oxidized) + H2O
∆ G0= - 112 kj.mol-1
Oxidative Phosphorylation
The transfer of electrons down the electron transport chain is energetically
favoured because NADH is a strong electron donor and molecular oxygen is an
avid electron acceptor
 ++++

++

The Proton Gradient Serves As The Common

Intermediate That Couples Oxidation To
Membrane transport systems
 ATP-ADP transport: The inner mitochondrial
membrane requires specialized carriers to transport
ADP and Pi from the cytosol (where ATP is used and
converted to ADP in many energy-requiring reactions)
into mitochondria, where ATP can be resynthesized.
 An adenine nucleotide carrier transports one molecule

of ADP from the cytosol into mitochondria, while

exporting one ATP from the matrix back into the cytosol
.
 This carrier is strongly inhibited by the plant toxin

atractyloside, resulting in a depletion of the

intramitochondrial ADP pool and cessation of ATP
Aproduction.
phosphate carrier is responsible for transporting
inorganic phosphate from the cytosol into
mitochondria.
Adenine Nucleotide and Phosphate
Translocases

Table 19-4
 The chemiosmotic theory of
oxidative phosphorylation

Complexes I, III, and The proton motive force

IV act as proton generated drives the
pumps creating a synthesis of ATP as the
proton gradient across protons flow back into the
the membrane, which matrix through the ATP
is negative on the synthase enzyme
matrix side
Re- entry of H+
across mitochondrial
membrane by 2,4-
dinitrophenol

Uncouplers increase the

permeability of the membrane
to ions, collapsing the proton
gradient by allowing the H+ to
pass across without going
through the ATP synthase, and
thus uncouple electron flow
through the respiratory
complexes from ATP synthesis.
 Uncoupling proteins
(UCP):
 These proteins create a “proton leak, they allow
protons to re-enter the mitochondrial matrix
without energy being captured as ATP .Energy is
released as heat, and the process is called
nonshivering thermogenesis.
 UCP1, also called thermogenin, is responsible for
the activation of fatty acid oxidation and heat
production in the brown adipocytes of mammals.
 Brown fat, unlike the more abundant white fat,
uses almost ninety percent of its respiratory
energy for thermogenesis in response to cold, at
birth, and during arousal in hibernating animals.
Complex I, NADH: ubiquinone oxidoreductase;
Complex II, succinate: ubiquinone oxidoreductase;
ComplexIII,
ubiquinol:ferricytochrome c
oxidoreductase;
Complex IV, ferrocytochrome
c:oxygen oxidoreductase

Sites Of Inhibition (− ) Of The Respiratory Chain By

Specific Drugs, Chemicals, And Antibiotics.
 Synthetic Uncouplers: 2,4-
dinitrophenol
◦ Electron transport and phosphorylation can also be
uncoupled by compounds that increase the
permeability of the inner mitochondrial membrane to
protons.
◦ The classic example is 2,4-dinitrophenol, a lipophilic
proton carrier that readily diffuses through the
mitochondrial membrane.
◦ This uncoupler causes electron transport to proceed at
a rapid rate without establishing a proton gradient,
much as do the UCPs Again, energy is released as heat
rather than being used to synthesize ATP.
◦ In high doses, the drug aspirin and other salicylates
uncouple oxidative phosphorylation. This explains the
fever that accompanies their toxic over dosage.
Transport of reducing
equivalents
 The inner mitochondrial membrane lacks
an NADH transport protein, and NADH
produced in the cytosol cannot directly
enter mitochondria.
 However, two electrons of NADH (i.e.,

reducing equivalents) are transported

from the cytosol into the mitochondria
using shuttle mechanisms:----
1) The Glycerophosphate Shuttle
2) The Malate-Aspartate Shuttle
The
Glycerophospha
te Shuttle
Malate-
Aspartate
Shuttle
Glycerol 3-
Phosphate
Shuttle
•Liver and heart utilize
malate-aspartate
shuttle and yield 3 ATP
per mol of NADH.
•Most of other tissues,
however, employ
Glycerol-Phosphate
shuttle and liberate 2
ATP from NADH.
The Creatine Phosphate Shuttle
Facilitates Transport of High-Energy
Phosphate from Mitochondria
 creatine phosphate shuttle acts as a
dynamic system for transfer of high-energy
phosphate from mitochondria in heart and
skeletal muscle.
 An isoenzyme of creatine kinase (CK )
m
found in the mitochondrial intermembrane
space, catalyzes phosphorylation of creatine
to creatine phosphate by using ATP.
 In turn, the creatine phosphate is transported

into the cytosol via protein pores in the outer

mitochondrial membrane, becoming available
for generation of extramitochondrial ATP.
Mechanism of oxidative
phosphorylation
 Several hypothesis have been proposed to
explain oxidative phosphorylation.
 The most important among them are:---

1) Chemical coupling
2) Chemiosmotic Hypothesis
Chemical Coupling Hypothesis
 ---Edward Slater (1953)
 --During the course of electron transfer in

respiratory chain, a series of

phosphorylated high energy intermediates
are first produced which are utilzed for the
synthesis of ATP.
 These reactions are analogous to substrate

level phosphorylation.
 NO EXPERIMENTAL EVIDENCE, as the high

energy intermediates have never been

isolated
CHEMIOSMOTIC THEORY
 Proposed by British Biochemist Peter
Mitchell in 1961. (Noble prize- 1978).
 The transport of protons from inside to
outside of inner mitochondrial membrane
results in generation of proton gradient
across the membrane.
 Protons accumulate outside the membrane
creating an electrochemical potential
difference.
The Chemiosmotic Theory Can Account for

Respiratory Control and the Action of

Uncouplers
 Due to this electrochemical potential, the
H+ ions flow back into mitochondrial matrix
down its electrochemical gradient through
a specific H+ (Fo) of ATP synthase
molecule.
 Free energy is released as H+ flows back

into lower H+ concentration zone.

 This free energy is coupled with

phosphorylation of ADP to ATP in F1 unit of

ATP synthase.
 ATP SYNTHASE (Complex V)
 It is a protein assembly in
inner mitochondrial
membrane.
 Sometimes referred to

as 5th complex.
 It has two functional

units, named as F1 and Fo.

Rotary Motor Model For ATP
Generation
 Proposed By Paul Boyer (1964) Nobel Prize
( 1997)
 A Conformational change in the

mitochondrial membrane proteins leads to

the synthesis of ATP
 Other names are:----
 -- Rotary motor model
 Engine driving model
 Bindig
Explains Thechange model
Synthesis Of ATP By The Proton
Gradient
•The enzyme ATP Synthase
is F0F1 complex (complex
V)
•The Fo subcomplex is
composed of channel
protein C subunits to which
F1-ATP synthase is
attached.
• F1-ATP synthase consists
of a central γ-subunit
surrounded
•In responsebytoalternating
the protonαflux ,the γ-subunit
and β subunit.(α3
physically rotates.and β3)
•This induces conformational changes in β3 –subunit
that finally leads to the release of ATP
A MEMBRANE LOCATED ATP
SYNTHASE FUNCTIONS AS A
ROTARY MOTOR
 According to the binding
change mechanism the
three β subunits of F1 –
ATP synthase adopt
different conformations.

•One subunit has open

(O) conformation ,
• The second has
loose(L) conformation
while
• The third one has
tight(T) conformation.
 ATP SYNTHASE-- A
ROTARY MOTORADP &
The substrates
Pi bind to β subunit
in L – conformation.
 The L site changes

to T conformation ,
and this leads to ATP
synthesis.
 The O site changes to

L – conformation
which binds to ADP&
Pi.
 The T site changes toThis cycle of conformation
change of β subunit is repeated
O- conformation, and
& three ATP are generated for
releases ATP.
each revolution
Mechanism of ATP
production----Summary
 The enzyme complex consists of an F0
subcomplex
which is a disk of “C” protein subunits.
 Attached with it is a γ-subunit in the form of

a “bent axle.”
 The γ-subunit fits inside the F1 subcomplex

of three α- and three β-subunits , which are

fixed to the membrane and do not rotate.
 ADP and Pi are taken up sequentially by the

β-subunits to form ATP, which is expelled as

the rotating γ-subunit squeezes each β-
subunit in turn.
 Thus, three ATP molecules are generated per
Oxidative Phosphorylation

 Oxidative phosphorylation The coupling of

oxidation with phosphorylation is termed oxidative
phosphorylation.
 The process produces more than 90 percent of the ATP
used by body cells.
 Peter Mitchell in 1961 (Nobel Prize 1978) proposed this
theory to explain the oxidative phosphorylation. The
transport of protons from inside to outside of inner
mitochondrial membrane is accompanied by the
generation of proton gradient across the membrane.
 Protons accumulate outside the membrane creating an
electrochemical potential difference.This proton motive
force drives the synthesis of ATP by ATP synthase.
Fig. 25-5, p. 923
Fig. 25-5b, p. 923
MECHANISM OF ATP SYNTHESIS

 Translocation of protons carried out by the

Fo catalyses the formation of
phosphoanhydride bond of ATP by
F1.Coupling of the dissipation of proton
gradient with ATP synthesis ( oxidatve
phosphorylation ) is through the interaction
of F1 & Fo
 BINDING CHANGE MECHANISM

PROPOSED BY PAUL BOYER NOBEL

PRIZE 1997 EXPLAINS THE SYNTHESIS
OF ATP BY THE PROTON GRADIENT.
THE ATP SYNTHASE IS
MOLECULAR MACHINE
 COMPARABLE TO A WATER DRIVEN HAMMER
,MINTING COINS
 F o is the WHEEL, Flow of protons is the

water fall.and the structural changes in F1

lead to ATP COIN BEING MINTED FOR EACH
TURN OF THE WHEEL.
 THE F1 HAS 3 CONFORMATION STATES FOR

THE ALPHA BETA FUNCTIONAL UNIT

 O STATE—DOES NOT BIND SUBSTRATE OR
PRODUCTS.
 L STATE-LOOSE BINDING OF SUBSTRATE

AND PRODUCTS.
 T STATE– TIGHT BINDING OF SUBSTRATE

AND PRODUCTS
 According to this theory, the 3 beta

subunits (catalytic sites)are in three

functional states.
THE BOND IS SYNTHESIZED IN THE T STATE
AND ATP IS RELEASED IN THE O STATE.
THIS IS KNOWN AS CONFORMATION THEORY
OF ATP SYNTHESIS
O –FORM IS OPEN &HAS NO
AFFINITY FOR SUBSTRATES
 L- FORM BINDS THE SUBSTRATE WITH
SLUGGISH AFFINITY
 T FORM BINDS SUBSTRATE TIGHTLY

&CATALYSES ATP SYNTHESIS.

 AS PROTONS TRANSLOCATE TO THE

MATRIX ,THE FREE ENERGY IS RELEASED

AND THIS IS HARNESSED TO INTERCONVERT
THESE THREE STATES .
THE BOND IS SYNTHESIZED IN THE
T STATE AND ATP IS RELEASED IN
THE O STATE.
THIS IS KNOWN AS CONFORMATION
THEORY OF ATP SYNTHESIS
INHIBITORS OF OXIDATIVE
PHOSPHORYLATION
 ATRACTYLOSIDE –INHIBITS THE
TRANSLOCASE
 OLIGOMYCIN-INHIBITS FLOW OF PROTONS

THROUGH Fo
 Ionophores e.g. Valinomycin allows

potassium to permeate mitochondria and

dissipate the proton gradient.
UNCOUPLERS OF OXIDATIVE
PHOSPHORYLATION
 2,4-Dinitrophenol
 2,4-Dinitrocresol
 CCCP-CHLOROCARBONYLCYANIDEPHENYL

HYDRAZONE.
 Physiological Uncouplers-
 Thyroxine –In high doses
 Thermogenin[Uncoupler protein] in brown

adipose tissue. In hibernating animals

&infants heat is reqd to maintain body
temperature.
Fig. 25-6, p. 925
Fig. 25-6, part 1, p. 925
Fig. 25-6, part 2, p. 925
Fig. 25-6, part 3, p. 925
Fig. 25-6, part 4, p. 925