Respiratory chain, its
role in energy capture and its control
Objective
• At the end of this lecture, student
will be able to
– Explain Respiratory chain
– Describe structural organisation of
ETC
– Discuss components of ETC
– Discuss Inhibitor of ETC
Electron Transport Chain
• The
energy rich carbohydrates, fatty acid and amino acid undergo a series of
metabolic reaction and are finally oxidized to CO2 and H2O
• The reducing equivalents from
various metabolic intermediates are transferred to coenzymes NAD+
and FAD to produce NADH & FADH2
• The
latter two reduced coenzymes
pass through ETC and finally, reduce oxygen to water
• The passage of electrons through the
ETC is associated with the loss of free energy
• A part of this free energy is
utilized to generate ATP from ADP and Pi
Mitochondria: The power houses
of cell
• Mitochondria are the centres for
metabolic oxidative reactions to generate reduced co-enzymes (NADH & FADH2)
which are utilized in ETC to liberate energy in the form of ATP. Hence,
regarded as the power house of the cell
• It consists of 5 distinct parts,
outer membrane, inner membrane, inter-membrane space, cristae and matrix
• ETC & ATP synthesizing system
are located on the inner mitochondrial membrane, which is a specialized
structure, rich in proteins. It is impermeable to ions (H+, K+,
Na+) and small molecules (ADP, ATP)
• This membrane is highly folded to
form cristae
– increases the inner surface area
• The inner surface consist of
phosphorylating subunits which are the centres for ATP production
• Matrix is rich in enzymes
responsible for the citric acid cycle, β-oxidation of
fatty acids and oxidation of amino acids
Structural organization of
respiratory chain
• The inner mitochondrial membrane
consist of five distinct respiratory or enzyme complexes, denoted as complex I
Il, III, IV and V
• The complexes l-lV are carriers of
electrons while complex V is responsible for ATP synthesis
• NADH, coenzyme Q, cytochrome C and
oxygen are mobile electron carriers in the respiratory chain
• The enzyme complexes (I-IV) and the
mobile carriers are collectively involved in the transport of electrons which,
ultimately, combine with oxygen to produce water
• The largest proportion of the oxygen
supplied to the body is utilized by the mitochondria for the operation of electron
transport chain
Components and reactions of
ETC
• Five distinct carriers in ETC
• These carriers are sequentially
arranged and are responsible for the transfer of electrons from a given
substrate to ultimately combine with proton and oxygen to form water
l. Nicotinamide nucteotides:
• Two coenzymes NAD+ &
NADP+ derived from the vitamin niacin, NAD+ is more
actively involved in the ETC
• NAD+ is reduced to NADH +
H+ by dehydrogenases with the removal of two hydrogen atoms from the
substrate (AH2)
e.g. glyceraldehyde-3-phosphate,
pyruvate, isocitrate, α-ketoglutarate and maleate
• NADPH + H+ produced by
NADP+dependent dehydrogenase is not used in a substrate for ETC. NADPH is more effectively utilized
for anabolic reactions (e.g. fatty acid synthesis, cholesterol synthesis)
2. Flavoproteins:
• The enzyme NADH dehydrogenase is a
flavoprotein with FMN as the prosthetic group. The coenzyme FMN accepts two
electrons and form FMNH2
• NADH dehydrogenase is a complex
enzyme closely associated with non-heme iron proteins (NHI) or iron-sulfur
proteins (FeS)
• Succinate dehydrogenases is an enzyme found in the inner
mitochondrial membrane. lt is also a flavoprotein with FAD as the coenzyme. It
can accept two hydrogen atoms from succinate
3. Iron sulfur (FeS) proteins:
• FeS proteins exist in the oxidized
(Fe3+) or reduced (Fe2+) state
• One FeS participates in the transfer
of electrons from FMN to coenzyme Q
• Other FeS proteins associated with
cytochrome b and cytochrome c1 participate in the transport of
electrons
4. Coenzyme Q (ubiquinone):
• lt is a quinone derivative with a
variable isoprenoid side chain
• The mammalian tissues possess a
quinone with 10 isoprenoid units which is known as coenzyme Q10
• Coenzyme Q is a lipophilic electron
carrier- lt accepts electrons from FMNH2 produced in the ETC by NADH dehydrogenase
5. Cytochromes:
• The cytochromes are conjugated
proteins containing heme group, consists of a porphyrin ring with iron atom
• The iron of heme in cytochromes is
alternately oxidized (Fe3+) & reduced (Fe2+), which
is essential for the transport of electrons in the ETC
• Three cytochromes were initially
discovered from the mammalian mitochondria- designated as cytochrome a, b &
c depending on the type of heme present and the respective absorption spectrum
• Additional cytochromes such as c1,
b1, b2, a3 etc were discovered later
Inhibitors of ETC
• The inhibitors bind to one of the
components of ETC and block the transport of electrons & causes the
accumulation of reduced components
• The synthesis of ATP is dependent on
electron transport. Hence, all the
site-specific inhibitors of ETC also inhibit ATP formation
• 3 possible sites
1. NADH and coenzyme Q : Fish poison, rotenone, barbiturate
drug amytal and antibiotic piercidin A inhibit this site
2. Between cytochrome b and c1: Antimycin A – an antibiotic,
British antilewisite (BAL) –an antidote used against war-gas-are the two
important inhibitors of the site between cytochrome b and c1
3. Inhibitors of cytochrome oxidase: Carbon monoxide, cyanide, hydrogen
sulphide and azide effectively inhibit cytochrome oxidase
Summary
• The
energy rich carbohydrates, fatty acid and amino acid undergo a series of
metabolic reaction and finally oxidized to co2 and H2O
• The passage of electrons through the
ETC is associated with the loss of free energy and part of this free energy is
utilized to generate ATP from ADP and Pi
• Mitochondria are the centres for ETC
• The
components of ETC are nicotinamide, Flavoproteins, Iron sulfur proteins,
Coenzyme Q
• Fish poison, rotenone, barbituate
drug amytal, piercidin A, Antimycin A, British antilewisite (BAL), Carbon
monoxide, cyanide, hydrogen sulphide and azide are inhibitors of ETC