Respiratory Chain [Electron Transport Chain] & Oxidative

Phosphorylation (1st lecture)

Why we study the respiratory chain? (Objective)
1- To describe the structure of mitochondria & indicate the location of
respiratory chain.
2- To appreciate the energy liberated in mitochondria.
3- To describe the four protein complexes involved in the transfer of
electrons through the respiratory chain.
4- To describe the structure of ATP synthase & explain how it works.
5- To identify the conditions controlling the rate of respiration in
mitochondria.
6- To know the the defects in the respiratory chain & its types.
7- To describe the permeability of inner mitochondrial membrane.
8- To describe the substrate shuttle & its types.
9- To describe how the rapid transport of high-energy phosphate in
active tissues occurs.

Mitochondria
By respiratory chain more energy is provided, it takes place inside the
mitochondria ((powerhouses)).
Mitochondria consists of the following:
‫نفاذ‬
1-Outer membrane: Permeable to most metabolites.
2-Inner membrane: Selectively permeable, consists of many folds or
cristae; it contains the enzymes of respiratory chain, ATP synthase &
‫ يتكون من العديد من الطيات‬، ‫ قابل للنفاذ بشكل انتقائي‬:‫الغشاء الداخلي‬
various membrane transporters. ATP‫ أو‬synthase ، ‫ ؛ أنه يحتوي على إنزيمات سلسلة الجهاز التنفسي‬cristae
3-Intermembrane space. .‫ومختلف ناقالت الغشاء‬
4-Matrix: Contains mainly the citric acid cycle enzymes.

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 Respiratory Chain [Electron Transport Chain]
The respiratory chain collects the reducing equivalents (Hydrogen or
electrons) for oxidation & coupled generation of ATP in a process called
oxidative phosphorylation.
The sources of these reducing equivalents are-
1- Major source: Within the mitochondria from the citric acid cycle
which is the final common pathway for aerobic metabolism of
carbohydrate, lipid & protein. .‫وهو املسار املشترك األخير لعملية التمثيل الغذائي الهوائية للكربوهيدرات والدهون والبروتني‬
2- Minor source: From the extramitochondrial reducing equivalents
that enter mitochondria through the mechanism known as
substrate shuttles to be collected by the respiratory chain.

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 Components of Respiratory Chain
The respiratory chain contains four large protein complexes
embedded in the inner mitochondrial membrane; these complexes are:
1) Complex I (NADH-Q oxidoreductase).
2) Complex II (succinate-Q reductase).
3) Complex III (Q-cytochrome oxidoreductase).
4) Complex IV (cytochrome oxidase).
Note:
-Riboflavin (FMN or FAD) as the coenzymes or hydrogen carriers are
important components of respiratory chain complexes where FMN is
found in complex I while FAD is found in complex II where both FMN or
FAD can be reduced to FMNH2 or FADH2 respectively.
-Iron-sulfur proteins (Fe-S) are found in Complexes I, II & III, it takes
part in electron transfer reactions.

Mechanism of Respiratory Chain

By the actions of respiratory chain two processes occur, which are:
1-Oxidation.
2-Phosphorylation. ‫متعلقان‬
Both oxidation & phosphorylation are correlated with each other & the
whole process is called oxidative phosphorylation.
1-Oxidation: - In oxidation the fate of hydrogens that enter the
respiratory chain are the following:
1- Their electrons (reducing equivalents) are transferring through the
components of respiratory chain in a series of oxidation reduction
reactions, (therefore, respiratory chain is also called electron
transport chain).
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 2- As a result of redox potential that produced from the series of
oxidation reduction reactions, the hydrogen ions (proton) are
transferred from the mitochondrial matrix to cross the inner
membrane into intermembrane space (proton pump).
‫تتاكسد‬
3- Finally, the hydrogens are oxidized into water.
These processes occur through the following mechanism which started
from lower to higher redox potential:
-In Complex I (NADH-Q oxidoreductase); NADH + H+ are formed
mainly by citric acid cycle & to less extent from pyruvate & ketone
bodies. In this complex, there is a transfer of:
1- Reducing equivalent from NADH + H+ to FMN then to a series of Fe-
S & finally to coenzyme Q forming QH2.
2- Four H+ from the matrix cross the inner membrane into
intermembrane space (translocation).
-In Complex II (succinate-Q reductase); It presents sometimes
instead of complex I in which FADH2 is formed during conversion of
succinate to fumarate in the citric acid cycle. In this complex, there is a
transfer of reducing equivalents from FADH2 then to a series of Fe-S to
coenzyme Q forming QH2, & it is not associated with transfer of H+ from
the matrix cross the inner membrane to intermembrane space (No
translocation).
-In Complex III (Q-cytochrome oxidoreductase); In this complex
there is a transfer of:
1- Reducing equivalents from QH2 to a series of cytochromes enzymes
(considered as dehydrogenase enzymes) in the presence of Fe-S
producing reduced cytochromes.
2- Four H+ from the matrix cross the inner membrane into
intermembrane space (translocation).
Therefore, ubiquinone (coenzyme Q) acts as a mobile component of
respiratory chain that collects reducing equivalent & passes them on to
the cytochromes,
-In Complex IV (cytochrome oxidase); In this complex, there is a
transfer of:
1- Reducing equivalents from reduced cytochromes into the oxygen to
form water after the binding of this oxygen with proton (hydrogen ion),
so the process required the presence of oxygen, therefore, the final
result is that the reduced cytochromes is oxidized with the formation of
H2O, this process is catalyzed by cytochrome oxidase (cytochrome
aa3) enzyme.

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2- Two H+ from the matrix cross the inner membrane to intermembrane
space (translocation).

2-Phosphorylation: - As a result of the passage of reducing

equivalents through respiratory chain complexes, there is a
phosphorylation of ADP by high energy phosphate (P) forming ATP, this
process is catalyzed by ATP synthase enzyme, then ATP gives its high
energy phosphate to the body & reconverted into ADP to be recycled
again in a process called ATP/ ADP cycle.
When oxidation in respiratory chain occurs via NADH+H+ (Complexes
I, III & IV) 2.5 mol of ATP are generated per half mol of O2 consumed
while only 1.5 mol of ATP are generated per half mol of O2 consumed
when oxidation occurs via FADH2 (Complexes II, III & IV).
The mechanism of phosphorylation (chemiosmotic theory) is discussed
later.
In fact, there are three major sources of ATP in the body, which are-
1-Respiratory chain: - The greatest quantitative source.
2-Glycolysis (at substrate level).
3-Citric acid cycle (at substrate level).

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 ‫الشروط التي تحدد‬
‫توفر‬ Conditions Limiting the Rate of Respiration
1-Availability
‫قدرة‬
of ADP and/or the substrate.
2-The‫توفر‬capacity of respiratory chain.
3-Availability of oxygen.

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