The electron transport chain is the final pathway where electrons from nutrients are transferred to oxygen to form water. Electrons enter the chain from NADH or FADH2 and are passed through four complexes and coenzyme Q, which pump protons out of the mitochondrial matrix. This creates a proton gradient that is used by ATP synthase to phosphorylate ADP and make ATP via oxidative phosphorylation. The chemiosmotic hypothesis explains this coupling of electron transport to ATP synthesis.

1. Electron transport chain
It is the final common pathway in aerobic cells by which
electrons derived from (CHO, amino acids and fatty acids)
can use respiratory chain as a final pathway as they give
electrons to oxidized co enzymes NAD+ and FAD+ to form
the energy rich reduced coenzymes NADH+ , FADH2

2. Then NADH+ , FADH2 give hydrogen and a pair of
electrons to electron transport chain to form water

3. Electron transport is coupled with formation of
proton gradient → used for ATP synthesis
• ETC Consists of 5 complexes:
– Complex I (NADH dehydrogenase)
– Complex II (Succinate dehydrogenase)
– Complex III (Cytochrome bc1 complex)
– Complex IV (Cytochrome a+a3 oxidase)
– Complex V (ATP synthase)

4. Organization of mitochondrial
electron transport chain
Complex I NADH Dehydrogenase
- oxidizes NADH
- transfers e- to Ubiquinone (UQ)
- pumps 1H+ per of electrons
It oxidizes NADH+H into NAD.at the same time
converts its coenzyme FMN into FMNH2

5. Complex II : Succinate Dehydroganase
- oxidation of succinate (from citric acid cycle)
- Electrons - are transferred via FADH2
- does not pump protons

6. Complex III Cytochrome bc1 complex
- oxidizes reduced UQ
- - pumps 1H+ per e
- Complex IV Cytochrome a+a3
- reduces O2 to H2O
- pumps 1H+ per e-
Complex V ATP synthase
- uses electrochemical proton gradient
to synthesize ATP

7. Coenzyme Q:
It is quinine derivative ,it is a relatively mobile
electron carrier.
Coenzyme Q can accept hydrogen atoms both from
FMNH2 produced by NADH dehydrogenase
(complex I) and from FADH2 which is produced by
succinate dehydrogenase and other similar
enzymes (complex II)

8. Cytochromes
There are 4 types of cytochromes (b, c, a and a3)
All cytochromes are conjugated proteins formed of
protein conjugated with heme ring. the heme ring
contains iron (fe) this iron oscillates between ferric
(fe+3) when it loses an electron, and ferrous (fe+2)
when it accepts electron.

9. Inhibitors of respiratory chain
Are compounds prevent the passage of electrons by
binding to a components of the chain,blocking the
oxidation , reduction reaction.
There are specific sites for binding inhibitors:
Site 1: binding with complex 1 preventing passage
of electrons from FMN to coenzyme Q.
e.g (Barbiturates and piericidin A)

10. Site II: preventing passage of electrons from
cytochrome b to cytochrome c.
e.g.(Antimycin A & dimercaprol)
Site III: preventing passage of electrons from
cytochrome a+a3 to o2.
e.g.(H2S, cyanide (CN-), carbon monoxide and
sodium a zide).

11. Inhibition of the respiratory chain also inhibits
ATP synthesis because ETC and oxidative
phosphorylation are tightly coupled

13. Release of free energy during ETC
Free energy is released as electrons are transferred
along the ETC from electron donor(reducing agent)
to an electron acceptor (oxidizing agent). The
electrons can be transferred in different forms e.g.
1. As hydride ion (H) to NAD+
2. As hydrogen atoms (H) to FAD
3. As electrons (e) to cytochromes

14. At three sites, the free energy released is sufficient
to support the phosphorylation of ADP to ATP,
which required about 7 kcal/mol.
Electrons that inter the respiratory chain through
the NAD-Q support the synthesis of 3mol of ATP. By
contrast ,electrons join the chain directly at the
level of coenzyme Q (as in case of FADH2 of
succinate dehydrogenase) will only support the
synthesis of 2mol of ATP.

15. Oxidative phosphorylation
Electrons are transported down the respiratory
chain from donor (NADH &FADH) to acceptor
oxygen.
The flow of electron from donor to acceptor
(oxidation) results in ATP synthesis by
phosphorylation of ADP by inorganic phosphate Pi
(phosphorylation). Therefor ,there is a coupling
between oxidation and phosphorylation.

16. Chemiosmotic hypothesis
1. Proton pump
The transport of electrons down the respiratory chain
give energy.
This energy is used to transport H+ from the
mitochondrial matrix across inner mitochondrial
membrane to inter membrane space(because outside
of the membrane (lower PH & more positive charges).
This done by complexes I,III and IV.
The energy generated by this proton gradient is
sufficient for ATP synthesis.

17. ATP synthase (complex V)
In the inner mitochondrial, there is a
phosphorylating enzyme complex: ATP snthase
It is formed of 2 subunits:
1. F1 subunit which protrude into matrix.
2. Fο subunit which present in the membrane.
The protons outside the inner mitochondrial
membrane can reenter mitochondrial matrix by
passing through channel (F1- Fο) to pass by ATP
synthase enzyme which is present in F1 subunit.
This results in synthesis of ATP from ADP + Pi.

18. Uncouplers
These are substances that allow oxidation to
proceed but prevent phosphorylation, so energy
released by electron transport will be lost in the
form of heat. This explains the cause of hotness
after intake of these substances. Examples:
Oligomycin,2.4 Dinitrophenol, Ca,high doses of
aspirin.