FirstRanker Logo

FirstRanker.com - FirstRanker's Choice is a hub of Question Papers & Study Materials for B-Tech, B.E, M-Tech, MCA, M.Sc, MBBS, BDS, MBA, B.Sc, Degree, B.Sc Nursing, B-Pharmacy, D-Pharmacy, MD, Medical, Dental, Engineering students. All services of FirstRanker.com are FREE

📱

Get the MBBS Question Bank Android App

Access previous years' papers, solved question papers, notes, and more on the go!

Install From Play Store

Download MBBS Electron Transport Chain Lecture PPT

Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Electron Transport Chain Lecture PPT

This post was last modified on 30 November 2021


ELECTRON TRANSPORT

CHAIN

--- Content provided by FirstRanker.com ---

DR. S. SHEKHAR

ASSOC. PROFESSOR

DEPT. OF

--- Content provided by FirstRanker.com ---


BIOCHEMISTRY


SYNTHESIS OF ATP

--- Content provided by FirstRanker.com ---


ATP can be synthesized in two

ways

--- Content provided by FirstRanker.com ---

1. Oxidative phosphorylation:
Major source of ATP in aerobic

organisms.

--- Content provided by FirstRanker.com ---

It is linked with mitochondrial

ETC.

2.

--- Content provided by FirstRanker.com ---


Substrate

level

--- Content provided by FirstRanker.com ---

phosphorylation:

When the energy of high energy

compound

--- Content provided by FirstRanker.com ---


is

directly

--- Content provided by FirstRanker.com ---



transferred

to

--- Content provided by FirstRanker.com ---


nucleoside

diphosphate

--- Content provided by FirstRanker.com ---

to

form

a

--- Content provided by FirstRanker.com ---


triphosphate without the help
from ETC.


--- Content provided by FirstRanker.com ---

The high-energy compounds such as
? PEP
? 1,3-bisphosphoglycerate
? Succinyl CoA
can transfer high-energy phosphate to ultimately

--- Content provided by FirstRanker.com ---


produce ATP.

STORAGE FORMS
? Phosphocreatine ( creatine phosphate)

--- Content provided by FirstRanker.com ---

? Provides high energy reservoir of ATP to regenerate

ATP rapidly, catalyzed by creatine kinase.

? Stored mainly in Muscle, Heart & Brain.

--- Content provided by FirstRanker.com ---

BIOLOGICAL OXIDATION

The transfer of electrons from the reduced

coenzymes through the respiratory chain to

--- Content provided by FirstRanker.com ---

oxygen is known as biological oxidation.

Energy released during this process is trapped

as ATP.

--- Content provided by FirstRanker.com ---


This

coupling

--- Content provided by FirstRanker.com ---

of

oxidation

with

--- Content provided by FirstRanker.com ---


phosphorylation

is

--- Content provided by FirstRanker.com ---

called

oxidative

phosphorylation.

--- Content provided by FirstRanker.com ---

TRANSPORT OF REDUCING EQUIVALENT

:SHUTTLE PATHWAY

? The inner mitochondrial is impermeable to

--- Content provided by FirstRanker.com ---


NADH.

? Therefore, the NADH produced in the cytosol

--- Content provided by FirstRanker.com ---

cannot directly enter the mitochondria.

? Two pathways
A. Glycerol-phosphate shuttle- In muscle and

--- Content provided by FirstRanker.com ---

brain

B. Malate-aspartate shuttle - In liver and heart
GLYCEROL-PHOSPHATE SHUTTLE

--- Content provided by FirstRanker.com ---

? Cytosolic glycerol 3-phosphate dehydrogenase

oxidizes NADH to NAD+

? The reducing equivalents are transported

--- Content provided by FirstRanker.com ---


through glycerol 3-phosphate into the
mitochondria.

? Glycerol 3-phosphate dehydrogenase-present

--- Content provided by FirstRanker.com ---


on outer surface of inner mitochondrial
membrane ? reduces FAD to FADH2.
.

--- Content provided by FirstRanker.com ---

? Dihydroxyacetone phosphate (DHAP) escapes

into the cytosol & the shuttling continues.

? FADH2 gets oxidized via ETC to generate

--- Content provided by FirstRanker.com ---


1.5ATP


GLYCEROL PHOSPHATE SHUTTLE

--- Content provided by FirstRanker.com ---

MALATE-ASPARTATE SHUTTLE

? In the cytosol, oxaloacetate accepts the

reducing equivalents (NADH) & becomes

--- Content provided by FirstRanker.com ---


malate.

? Malate enters the mitochondria where it is

--- Content provided by FirstRanker.com ---

oxidized by mitochondrial MDH

? In this reaction, NADH & oxaloacetate are

regenerated.

--- Content provided by FirstRanker.com ---


? NADH gets oxidized via ETC & 2.5 ATP are

produced.

--- Content provided by FirstRanker.com ---


MALATE-ASPARTATE SHUTTLE .


? In the mitochondria, oxaloacetate participates

--- Content provided by FirstRanker.com ---


in transamination reaction with glutamate to
produce aspartate & ketoglutarate.

? The aspartate enters the cytosol &

--- Content provided by FirstRanker.com ---


transaminates with -ketoglutarate to give
oxaloacetate & glutamate.
REDOX POTENTIAL

--- Content provided by FirstRanker.com ---

Oxidation:
? Oxidation is defined as the loss of electrons
and reduction as the gain in electrons.

? When a substance exists both in the reduced

--- Content provided by FirstRanker.com ---


state & in the oxidized state, the pair is called a
redox couple.


--- Content provided by FirstRanker.com ---

Redox potential(E0):
? The oxidation-reduction potential or redox

potential, is a quantitative measure of the
tendency of a redox pair to lose or gain

--- Content provided by FirstRanker.com ---

electrons.

? The redox pairs are assigned specific standard

redox potential at pH 7.0 & 250C

--- Content provided by FirstRanker.com ---



? The more negative redox potential represents a

greater tendency to lose electrons.

--- Content provided by FirstRanker.com ---


? A more positive redox potential indicates a

greater tendency to accept electrons

--- Content provided by FirstRanker.com ---

? The electrons flow from a redox pair with more

negative E0 to another redox pair with more

positive E0

--- Content provided by FirstRanker.com ---


? The redox potential (E0) is directly related to

the change in the free energy (G0)

--- Content provided by FirstRanker.com ---



ELECTRON TRANSFER CHAIN

? The flow of electrons occurs through

--- Content provided by FirstRanker.com ---


successive

dehydrogenase

--- Content provided by FirstRanker.com ---

enzymes

in

mitochondria , together known as the ETC.

--- Content provided by FirstRanker.com ---

(the electrons are transferred from higher to
lower potential.)

Significance:
? The free energy released during the transport

--- Content provided by FirstRanker.com ---

of electrons is utilized for the formation of ATP


MITOCHONDRIAL ORGANIZATION

--- Content provided by FirstRanker.com ---

? Mitochondria consists of five distinct parts
? Outer membrane, inner membrane, intermembrane

space, cristae & matrix

--- Content provided by FirstRanker.com ---


Inner mitochondrial membrane:
? The ETC & ATP synthesizing system are located on

inner mitochondrial membrane, which is specialized

--- Content provided by FirstRanker.com ---

structure, rich in proteins

? Inner membrane is highly folded to form cristae.
? Surface area of inner mitochondrial membrane is

--- Content provided by FirstRanker.com ---

increased due to cristae.

? The inner surface of inner mitochondrial membrane

possesses specialized particles, the phosphorylating

--- Content provided by FirstRanker.com ---

subunits which are centres for ATP production.


2H+

--- Content provided by FirstRanker.com ---

4H+

Organisation of electron transport chain and route-

map of electron flow through ETC.

--- Content provided by FirstRanker.com ---


ETC consists of four enzymes complexes & two

free electron carriers

--- Content provided by FirstRanker.com ---

Complex I: NADH-ubiquinone oxidoreductase
Complex II: Succinate dehydrogenase
Complex III: Ubiquinol cytochrome oxidoreductase
Complex IV: Cytochrome oxidase
? Two free electron carriers are coenzyme Q &

--- Content provided by FirstRanker.com ---


Cytochrome C.

? Complex V: It is ATP synthase.
? The complexes I-IV are carriers of electrons while

--- Content provided by FirstRanker.com ---


complex V is responsible for ATP synthesis.


? The enzyme complexes & mobile carriers are

--- Content provided by FirstRanker.com ---


collectively involved in the transport of
electrons which, ultimately, combine with
oxygen to produce water.

--- Content provided by FirstRanker.com ---

? Largest proportion of O2 supplied to body is

utilized by mitochondria for the operation of
ETC.
Complex I

--- Content provided by FirstRanker.com ---


? Of the two coenzymes NAD+& NADP+, NAD+

is more actively involved in ETC.

--- Content provided by FirstRanker.com ---

? Tightly bound to the inner membrane
? NAD+ is reduced to NADH + H+ by

dehydrogenases with the removal of two

--- Content provided by FirstRanker.com ---

hydrogen atoms from the substrates, the

substrates includes pyruvate, gly-3-P. etc.

? NADPH is more effectively utilized for

--- Content provided by FirstRanker.com ---


anabolic reactions - fatty acid synthesis,

cholesterol synthesis.

--- Content provided by FirstRanker.com ---


? The enzyme NADH dehydrogenase (NADH

coenzyme Q reductase) is a flavoprotein with FMN as
the prosthetic group.

--- Content provided by FirstRanker.com ---


? The coenzyme FMN accepts two electrons & a proton

to form FMNH2.

--- Content provided by FirstRanker.com ---

? NADH dehydrogenase is a complex enzyme closely

associated with non- heme iron proteins or iron-sulfur
proteins.

--- Content provided by FirstRanker.com ---

? In this, 4 protons are pumped out from mitochondria.
? NADH + H+ + FMN NAD+ + FMNH2
Complex II ? Succinate - Co Q- Reductase

? The electrons from FADH2 enter ETC at the level of

--- Content provided by FirstRanker.com ---


Co Q.

? Succinate DH is an enzyme found in inner

--- Content provided by FirstRanker.com ---

mitochondrial membrane.

? It is also a flavoprotein with FAD as coenzyme.
? The 3 major enzyme systems that transfer their

--- Content provided by FirstRanker.com ---

electrons directly to ubiquinone are:

a. Succinate dehydrogenase
b. Fatty acyl CoA dehydrogenase
c. Mitochondrial glycerol phosphate

--- Content provided by FirstRanker.com ---






--- Content provided by FirstRanker.com ---






--- Content provided by FirstRanker.com ---


dehydrogenase.



--- Content provided by FirstRanker.com ---

Iron-sulfur centers

? Iron-sulfur centers (Fe-S) are prosthetic groups

containing 1-4 iron atoms

--- Content provided by FirstRanker.com ---


? Iron-sulfur (Fe-S) proteins exist in the oxidized

(Fe3+) or reduced (Fe2+) state.

--- Content provided by FirstRanker.com ---

? Iron-sulfur centers transfer only one electron, even

if they contain two or more iron atoms

? Fe-S participates in the transfer of electrons from

--- Content provided by FirstRanker.com ---


FMN to coenzyme Q.

? Other Fe-S proteins associated with cytochrome b

--- Content provided by FirstRanker.com ---

& cytochrome c1 participate in the transport of

electrons.
Coenzyme Q

--- Content provided by FirstRanker.com ---

? It is also known as ubiquinone.
? It is a quinone derivative with isoprenoid side chain
? The ubiquinone is reduced successively to

semiquinone (QH) & finally to ubiquinol (QH2)

--- Content provided by FirstRanker.com ---


? It accepts a pair of electrons from NADH or

FADH2 through complex I or complex II

--- Content provided by FirstRanker.com ---

respectively.

? 2 molecules of cytochrome c are reduced.
? The Q cycle facilitates the switching from the 2

--- Content provided by FirstRanker.com ---

electron carrier ubiquinol to the single electron

carrier cytochrome c.

? This is a mobile carrier.

--- Content provided by FirstRanker.com ---






--- Content provided by FirstRanker.com ---


Complex III Cytochrome - Reductase

? This is a cluster of iron-sulphur proteins, cytochrome b

--- Content provided by FirstRanker.com ---

& cytochrome c1, both contain heme prosthetic group.

? Consists of a porphyrin ring with iron atom.
? The iron of heme in cytochromes is alternately oxidized

--- Content provided by FirstRanker.com ---

(Fe3+) & reduced (Fe2+ ) which is essential for transport
of electrons in the ETC.

? In this, 4 protons are pumped out.
? This complex transfers 2 electrons to cytochrome c from

--- Content provided by FirstRanker.com ---


2 molecules of CoQH2 along with the vectorial
movement of 4H+ from mitochondrial matrix to
intermembranous space.

--- Content provided by FirstRanker.com ---


? The property of



--- Content provided by FirstRanker.com ---

reversible oxidation reduction of

heme iron present in cytochromes allows them to
function as effective carriers of electrons in ETC.

--- Content provided by FirstRanker.com ---

? Cytochrome C:
It is a small protein containing 104 amino acids & a

heme group.

--- Content provided by FirstRanker.com ---

It is a loosely bound to inner mitochondrial

membrane & can be easily extracted.
Complex IV Cytochrome - Oxidase

--- Content provided by FirstRanker.com ---

? Contains cytochrome a and cytochrome a3 which

is the terminal component of ETC

? Tightly bound to inner mitochondrial membrane.

--- Content provided by FirstRanker.com ---

? Cytochrome oxidase is the only electron carrier,

heme iron of which can directly react with

molecular oxygen.

--- Content provided by FirstRanker.com ---


? It also contains copper that undergoes oxidation

reduction during transport of electrons.

--- Content provided by FirstRanker.com ---

? 2 protons are pumped out.
? In the final stage of ETC, the transported electrons,

the free protons & the molecular oxygen combine

--- Content provided by FirstRanker.com ---

to produce water




--- Content provided by FirstRanker.com ---


.
INHIBITORS OF ETC

? The inhibitors bind to one of the components of ETC

--- Content provided by FirstRanker.com ---


& block the transport of electrons

? This causes the accumulation of reduced

--- Content provided by FirstRanker.com ---

components before the inhibitor blockade step &
oxidized components after that step.

? The synthesis of ATP is dependent on ETC.
? All the site-specific inhibitors of ETC also inhibit

--- Content provided by FirstRanker.com ---


ATP formation.

Complex I: NADH & coenzyme Q
? Fish poison rotenone, barbiturate drug amytol &

--- Content provided by FirstRanker.com ---


antibiotic piercidin A inhibit this.


Complex II:

--- Content provided by FirstRanker.com ---

Carboxin inhibit this site.
Complex III Between cytochrome b & c1
? Antimycin A ?an antibiotic,
? British antilewisite (BAL) ?an antidote used

--- Content provided by FirstRanker.com ---

against war-gas

? Naphthoquinone are important inhibitors of the

site between cytochrome b & c1.

--- Content provided by FirstRanker.com ---



Cytochrome oxidase (Complex IV):


--- Content provided by FirstRanker.com ---

Carbon monoxide, cyanide, hydrogen sulphide

& azide

? Effectively inhibit cytochrome while cyanide &

--- Content provided by FirstRanker.com ---


azide react with oxidized form of cytochrome.

? Cyanide is most potent inhibitor of ETC
? It binds to Fe3+ of cytochrome oxidase blocking

--- Content provided by FirstRanker.com ---


mitochondrial respiration leading to cell death.

? Cyanide poisoning causes death due to tissue

--- Content provided by FirstRanker.com ---

asphyxia (mostly of CNS)


Site specific inhibitors of ETC.
Biological Oxidation:

--- Content provided by FirstRanker.com ---


? The transfer of electrons from the reduced co

enzymes though the respiratory chain to oxygen is
known as biological oxidation.

--- Content provided by FirstRanker.com ---


? Energy released during this process is trapped as

ATP.

--- Content provided by FirstRanker.com ---

? This coupling of oxidation with phosphorylation

is

called

--- Content provided by FirstRanker.com ---


as

OXIDATIVE

--- Content provided by FirstRanker.com ---

PHOSPHORYLATION.

? Complex V of the inner mitochondrial membrane

is the site of oxidative phosphorylation.

--- Content provided by FirstRanker.com ---

PHOSPHAGENS

? Phosphagens act as storage forms of high energy

phosphate and include creatine phosphate, which

--- Content provided by FirstRanker.com ---

occurs in vertebrate skeletal muscle, heart,
spermatozoa & brain.

? Arginine phosphate, in invertebrate muscle.

--- Content provided by FirstRanker.com ---

? When ATP is rapidly being utilized as a source of

energy for muscular contraction, phosphagens permit
its concentrations to be maintained, but when the
ATP/ADP ratio is high, their concentration can

--- Content provided by FirstRanker.com ---

increase to act as a store of high-energy phosphate.
SITES OF OXIDATIVE PHOSPHORYLATION

IN ETC

--- Content provided by FirstRanker.com ---

? There are 3 reactions in the ETC that are

exergonic,

Where the energy change is sufficient to

--- Content provided by FirstRanker.com ---


drive the synthesis of ATP from ADP and Pi.

? Site1:
Oxidation of FMNH2 by coenzyme Q.

--- Content provided by FirstRanker.com ---

? Site2:
Oxidation of cytochrome b by cytochrome c1
? Site3:
Cytochrome oxidase.
ENERGETICS OF OXIDATIVE

--- Content provided by FirstRanker.com ---


PHOSPHORYLATION

? ? O2 + NADH + H+ H2O + NAD+

--- Content provided by FirstRanker.com ---

The redox potential difference between these two redox

pairesis 1.14V, which is equivalent to an energy 52

Cal/mol

--- Content provided by FirstRanker.com ---


3 ATP are synthesized in ETC when NADH is

oxidized which equals to 21.9 Cal.

--- Content provided by FirstRanker.com ---

(each ATP=7.3 Cal)
The efficiency of energy conservation is calculated as
21.9 ? 100
52 = 42%
.

--- Content provided by FirstRanker.com ---


When NADH is oxidized, about 42% of energy
is trapped in the form of 3ATP & remaining is
lost as heat.
The heat liberation is not a wasteful process,

--- Content provided by FirstRanker.com ---

since it allows ETC to go on continuously to
generate ATP.
This heat is necessary to maintain body
temperature.
MECHANISM OF OXIDATIVE

--- Content provided by FirstRanker.com ---


PHOSPHORYLATION

? Two important hypothesis to explain the

--- Content provided by FirstRanker.com ---

process of oxidative phosporylation.

? Namely
Chemical coupling &
Chemiosmotic

--- Content provided by FirstRanker.com ---


Chemical coupling hypothesis:

? This hypothesis was put forth by Edward

--- Content provided by FirstRanker.com ---

Slater (1953)

? According to this, during the course of electron

transfer in respiratory chain, a series of

--- Content provided by FirstRanker.com ---


phosphorylated high-energy intermediates are

first produced which are utilized for the

--- Content provided by FirstRanker.com ---

synthesis of ATP.

? These reactions are believed to be analogous to

the substrate level phosphorylation that occurs

--- Content provided by FirstRanker.com ---


in glycolysis or citric acid cycle.

? This hypothesis lacks experimental evidence.

--- Content provided by FirstRanker.com ---


CHEMIOSMOTIC THEORY

Chemiosmotic theory,
proposed by Peter Mitchell

--- Content provided by FirstRanker.com ---

in 1961, postulates that the
two processes are coupled by
a proton gradient across the
inner

--- Content provided by FirstRanker.com ---

mitochondrial

membrane so that the proton
motive force caused by the
electrochemical

--- Content provided by FirstRanker.com ---


potential

difference (negative on the
matrix side) drives the

--- Content provided by FirstRanker.com ---

mechanism

of

ATP

--- Content provided by FirstRanker.com ---


synthesis.
.

? The transport of electrons through the

--- Content provided by FirstRanker.com ---


respiratory chain is effectively utilized to

produce ATP from ADP + Pi.

--- Content provided by FirstRanker.com ---

? PROTON GRADIENT:
The inner mitochondrial membrane, is

impermeable to protons (H+) & hydroxyl ions

--- Content provided by FirstRanker.com ---

(OH-).

The transport of electrons through ETC is

coupled with the translocation of protons

--- Content provided by FirstRanker.com ---


(H+)across the inner mitochondrial membrane

from the matrix to the inter membrane space.
.

--- Content provided by FirstRanker.com ---


? The pumping of protons results in an

electrochemical or proton gradient

--- Content provided by FirstRanker.com ---

? This is due to the accumulation of more H+ions

(low pH) on the outer side of the inner
mitochondrial membrane than the inner side.

--- Content provided by FirstRanker.com ---

? The proton gradient developed due to the

electron flow in the respiratory chain is
sufficient to result in the synthesis of ATP
from ADP +Pi.

--- Content provided by FirstRanker.com ---




Enzyme systems for ATP synthesis

--- Content provided by FirstRanker.com ---

? ATP synthase, present in the complex V, utilizes

the proton gradient for the synthesis of ATP.

? This enzyme is also known as ATPase, since it

--- Content provided by FirstRanker.com ---


can hydrolyze ATP to ADP + Pi.

? ATP synthase is a complex enzyme & consists of

--- Content provided by FirstRanker.com ---

two functional subunits, namely F1 & Fo.

? Fo unit: O stands for oligomycin,
? Fo inhibited by oligomycin.
? Fo spans inner mitochondrial membrane acting as

--- Content provided by FirstRanker.com ---


a proton channel through which protons enter the

mitochondria

--- Content provided by FirstRanker.com ---

? Fo unit has 4 polypeptide chains & is connected to

F1
.F1 UNIT

--- Content provided by FirstRanker.com ---

? F1 unit: It projects into the matrix.
? F1 has 9 polypeptide chains, (3 alpha, 3 beta, 1

gamma, 1 delta, 1 epsilon)

--- Content provided by FirstRanker.com ---

? The chains have binding sites for ATP & ADP

& beta chains have catalytic activity.

? ATP synthesis requires Mg +2 Ions.

--- Content provided by FirstRanker.com ---

? Its structure is comparable with lollipops.
? The

protons

--- Content provided by FirstRanker.com ---

that

accumulate

on

--- Content provided by FirstRanker.com ---


the

intermembrane space re-enter the mitochondrial
matrix leading to the synthesis of ATP

--- Content provided by FirstRanker.com ---


ROTOR MOTOR MODEL FOR ATP

GENERATION

--- Content provided by FirstRanker.com ---

? Paul Boyer in 1964 proposed that a conformational

change in the mitochondrial membrane proteins

leads to the synthesis of ATP

--- Content provided by FirstRanker.com ---


? This is now considered as rotary motor/engine

driving model or binding change model.

--- Content provided by FirstRanker.com ---

? widely accepted for the generation of ATP.
? The enzyme ATP synthase is Fo & F1 complex
? The Fo sub complex is composed of channel

protein `C' subunits to which F1-ATP synthase is

--- Content provided by FirstRanker.com ---


attached.
.

? F1-ATP synthase consists of a central gamma

--- Content provided by FirstRanker.com ---


subunit surrounded by alternating alpha & beta

subunits ( 3 & 3).

--- Content provided by FirstRanker.com ---

? In response to the proton flux, the gamma subunit

physically rotates.

? This induces conformational changes in the 3

--- Content provided by FirstRanker.com ---


subunits that finally lead to the release of ATP.

? According to the binding change mechanism, the

--- Content provided by FirstRanker.com ---

three subunits of F1 - ATP synthase adopt

different conformations.

? One subunit has Open (O) conformation, the

--- Content provided by FirstRanker.com ---


second has loose (L) conformation while the third

one has tight (T) conformation.
.

--- Content provided by FirstRanker.com ---


? By an known mechanism, protons induce the

rotation of gamma subunit, which in turn induces

--- Content provided by FirstRanker.com ---

conformation changes in subunits,.

? The substrates ADP & Pi bind to subunit in L

conformation.

--- Content provided by FirstRanker.com ---


? The L site changes to T conformation, & this

leads to the synthesis of ATP.

--- Content provided by FirstRanker.com ---

? The O site changes to L conformation which binds

to ADP + Pi.

? The T site changes to O conformation & releases

--- Content provided by FirstRanker.com ---


ATP.

? This cycle of conformation changes of subunits

--- Content provided by FirstRanker.com ---

is repeated.

? Three ATP are generated for each revolution.


--- Content provided by FirstRanker.com ---

.


BOYER'S BINDING CHANGE MODEL FOR ATP SYNTHESIS BY ATP SYNTHASE.
INHIBITORS OF OXIDATIVE PHOSPHORYLATION

--- Content provided by FirstRanker.com ---


? The mitochondrial transport of electrons is

tightly coupled with oxidative phosphorylation.

--- Content provided by FirstRanker.com ---

? Oxidation

&

phosphorylation

--- Content provided by FirstRanker.com ---


proceed

simultaneously.

--- Content provided by FirstRanker.com ---

? There are certain compounds that can uncouple

(or delink) the electron transport from oxidative

phosphorylation.

--- Content provided by FirstRanker.com ---


? Such compounds are known as uncouplers,
? Causes increase in the permeability of inner

mitochondrial membrane to protons (H+).

--- Content provided by FirstRanker.com ---


? The result is that ATP synthesis does not occur
.

? The energy linked with the transport of electrons

--- Content provided by FirstRanker.com ---


is dissipated as HEAT.

? The uncouplers allow (often at accelerated rate)

--- Content provided by FirstRanker.com ---

oxidation of substrates (via NADH or FADH2)

without ATP formation

? Examples:

--- Content provided by FirstRanker.com ---

? 2,4-dinitrophenol (DNP):
It is small lipophilic molecule.
DNP is a proton ? carrier & easily diffuse through

the inner mitochondrial membrane.

--- Content provided by FirstRanker.com ---


Others ?dinitrocressol, pentachlorophenol,

trifluorocarbonylcyanide, phenylhydrazone.
PHYSIOLOGICAL UNCOUPLERS

--- Content provided by FirstRanker.com ---


? Certain physiological substances which act as

uncouplers at higher concentration.

--- Content provided by FirstRanker.com ---

? These are thermogenin, thyroxine and long chain

fatty acids & unconjugated bilirubin

Significance of uncoupling:

--- Content provided by FirstRanker.com ---

The maintenance of body temperature is

particularly important in hairless animals,

hibernating animals & the animals adopted to cold

--- Content provided by FirstRanker.com ---


? These animals possess a specialized tissue called

brown adipose tissue in the upper back & neck

--- Content provided by FirstRanker.com ---

portions.
.

? The mitochondria of brown adipose tissue are rich in

--- Content provided by FirstRanker.com ---

electron carriers & are specialized to carry out an

oxidation uncoupled from phosphorylation.

? This causes liberation of heat when fat is oxidized in

--- Content provided by FirstRanker.com ---


the brown adipose tissue.

? The presence of brown adipose tissue in certain

--- Content provided by FirstRanker.com ---

individuals is believed to protect them from

becoming obese.

? Thermogenin is a natural uncoupler located in the

--- Content provided by FirstRanker.com ---


inner mitochondrial membrane of brown adipose

tissue

--- Content provided by FirstRanker.com ---

? It acts like an uncoupler, blocks the formation of

ATP, & liberates heat.
IONOPHORES

--- Content provided by FirstRanker.com ---

? Ionophores: These are lipophilic substances that

are lipid soluble and increases the permeability of

inner motochondrial membrane to ions and

--- Content provided by FirstRanker.com ---


thereby destroy the proton gradient leading to

inhibition of ATP synthesis.

--- Content provided by FirstRanker.com ---

? By either forming channel or
? By binding an ion and then diffusing into

membrane.

--- Content provided by FirstRanker.com ---

? Valinomycin ( binds with K+) & Nigercin also act

as uncouplers
INHIBITORS OF OXIDATIVE

--- Content provided by FirstRanker.com ---

PHOSPHORYLATION

? Oligomycin: This antibiotic binds with enzyme

ATP synthase & blocks the proton(H+)

--- Content provided by FirstRanker.com ---


channels.

? Thus it prevents the translocation (re-entry) of

--- Content provided by FirstRanker.com ---

protons into the mitochondrial matrix and

prevent ATP synthesis

? Atractyloside: It is a plant toxin & inhibits

--- Content provided by FirstRanker.com ---


oxidative phosphorylation.

? It blocks the adequate supply of ADP by

--- Content provided by FirstRanker.com ---

inhibiting ADP/ATP transporter
INHERITED DISORDER OF OXIDATIVE

PHOSPHORYLATION

--- Content provided by FirstRanker.com ---

? 100 polypeptides are required for oxidative

phosphorylation.

? Of these, 13 are coded by mitochondrial DNA

--- Content provided by FirstRanker.com ---


& synthesized in the mitochondria, while the
rest are produced in the cytosol (coded by
nuclear DNA) & transported.

--- Content provided by FirstRanker.com ---

? mtDNA is maternally inherited since

mitochondria from the sperm do not enter the
fertilized ovum.
.

--- Content provided by FirstRanker.com ---


? Mitochondrial DNA is 10 times more susceptible

to mutations than nuclear DNA.

--- Content provided by FirstRanker.com ---

? mtDNA mutations are commonly seen in tissues

with high rate of oxidative phosphorylation (e.g.

CNS, skeletal & heart muscle, liver).

--- Content provided by FirstRanker.com ---


? Diseases:
Lethal infantile mitochondrial opthalmoplegia
Leber's hereditary optic neuropathy (LHON)
Myoclonic epilepsy

--- Content provided by FirstRanker.com ---

Mitochondrial encephalopathy lactic acidosis

stroke like episodes (MELAS)


--- Content provided by FirstRanker.com ---


STRUCTUTRE OF ATP SYNTHASE.