The document summarizes the structure and function of the electron transport chain (ETC) located in the inner mitochondrial membrane. It describes the five protein complexes (I-IV and V) that make up the ETC and how they facilitate the transfer of electrons from donors like NADH to final acceptors like oxygen. This electron transfer is coupled to the pumping of hydrogen ions across the membrane, creating a proton gradient that Complex V uses to synthesize ATP via oxidative phosphorylation. Various inhibitors are also outlined that can disrupt electron transfer at different complexes or uncouple the proton gradient from ATP production.

1. Organization of ETC:
• Inner mitochondrial membrane can be disrupted into five separate
protein complexs , called Complexes I,II,III,IV & V.
• Complex I-IV each contains part of the ETC. Each complex accepts
or donates electrons to relatively mobile electron carrier, such as
coenzyme Q & cytochrome C.
• Each carrier in the ETC can receive electrons from an electron
donor, & can donate electrons to the next carrier in the chain.
• Electrons ultimately combine with oxygen & protons to form
water.
• Complex V is a protein complex, contains F0 that spans the IMM
and F1 protrudes into the matrix. It catalyses ATP synthesis & so
referred to as ATP synthase.
Site of ETC: Inner Mitochondrial
Membrane

2. Reactions of the ETC:

3. Complex I:
• NADH-CoQ reductase or NADH dehydrogenase complex.
• Contains a Fp consisting of FMN as prosthetic group & an Fe-S protein.
• 12 kcal/mol energy is released, utilized to drive 4 H+ .
Complex II:
Three major enzyme system that tranfers their electrons
directly to Co Q
i. Succinate dehydrogenase
ii. Fatty acyl CoA dehydrogenase
iii. Mitochondrial glycerol
phosphate dehydrogenase

4.  Coenzyme Q:
• Reduced successively to QH and finally QH2.
• Accepts a pair of electrons from NADH or FADH2 through Complex I or II.
• It is s Quinone derivative having a long isoprenoid tail
• It is the mobile electron carrier, transfers electrons to Complex III.
 Complex III:
• The free energy change is
-10 kcal/mol.
• 4 H+ is pumped out.
 Cytochrome C:
• Peripheral membrane Protein containing 1 heme prosthetic group.
• Collects electrons from Complex III & delivers to Complex IV.
• It is a soluble electron carrier which is a peripheral membrane
protein.
• So, any damage to mitochondrial membrane will lead to release of
Cytochrome C, which act as a trigger for apoptosis.

5.  Complex IV:
• Cytochrome Oxidase
• final stage of electron transport.
• The 4 electron reduction of oxygen to water is unique & uses only the
redox canters of Complex IV.
• Cytochrome oxidase contains 2 heme & 3 copper ions.
• Functional unit : Cytochrome a-a3.
 Oxidative Phosphorylation:
• Flow of electrons through the respiratory chain generates ATP
by the process of Oxidative phosphorylation.
• Oxidation coupled with Phosphorylation.
• Theory behind Oxidative phosphorylation: Chemiosmotic theory.

6.  Chemiosmotic theory:
• Proposed by Peter Mitchell
• Postulates that the two processes, Oxidation & Phosphorylation are
coupled by a proton gradient across the IMM.
• The proton motive force caused by the electrochemical potential
difference drives the mechanism of ATP synthesis.
 Complex V:
• ATP synthase Complex.
• Also called 5th complex of ETC.
• Smallest molecular motor present in the Human Body.
• Embedded in the IMM.
• Divided into 2 Subcomplex:
 F0 subcomplex
-Hydrophobic
-spans the IMM
-Forms a proton Channel

7.  F1 Subcomplex:
• Hydrophilic
• Projects into the mitochondrial matrix
• Attached to F0 subcomplex.
• Made up of 9 subunits ( 3 alpha, 3 beta, gamma, delta, epsilon
• Gamma subunit is surrounded by 3α and 3β subunit
alternatively.
• The flow of protons through F0 causes, rotation of F0 Complex
along with γ subunit of F1 complex to rotate
• This causes the production of ATP
in the F1 complex
• β subunit of F1 Complex is called
Catalytic Subunit.

8.  INHIBITORS OF ETC:
• Divided into
• Inhibitors of Electron transfer
• Inhibitors of Oxidative Phosphorylation
• Uncouplers of Oxidative Phosphorylation
• Ionophores
Inhibitors of Electron Transfer
 Between NADH and CoQ [At Complex I]
• An insecticide and a fish Poison Rotenone
• Amobarbital which is a barbiturate
• Piericidin A.
 Inhibitor of Complex II
• TTFA (Tri enoyl TriFluoroAcetone) a Fe2+ Chelating agent
• Carboxin
• Malonate, a competitive inhibitor of Succinate Dehydrogenase.
 Between Cyt b and Cyt c [At Complex III]
• Antimycin A
• British Antilevisite [Dimercaprol]
 Inhibitor at Cytochrome c Oxidase [Complex IV]
• CO
• Cyanide
• H2 S
• Sodium Azide

9. Inhibitors of Oxidative Phosphorylation
 Atractyloside
By inhibiting the transporter of ADP into and ATP out of the
mitochondrion.
 Oligomycin an Antibiotic
Completely blocks oxidation and phosphorylation. By blocking the
flow of protons through F0 Complex of ATP Synthase
Uncoupler of Oxidative Phosphorylation
Mechanism of Action—Disruption of Proton Gradient across the
inner mitochondrial membrane
• 2,4 Dinitrophenol
• Dinitrocresol
• FCCP [Fluoro Carbonyl Cyanide Phenyl hydrazine]
• Aspirin in high dose
 Physiological Uncouplers : Thyroxine (in high doses),
Thermogenin.

10. Ionophores
• Ionophores permit specifications to penetrate membranes
• Dissipate Proton Gradient
• Valinomycin
• Gramicidin
• Nigercin