Respiratory chain, its role in energy capture and its control

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

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