This document discusses the electron transport chain (ETC) and its components. It notes that the ETC is located in the inner mitochondrial membrane and utilizes electrons derived from nutrients to generate ATP through a series of oxidation-reduction reactions. It describes the five complexes of the ETC (Complexes I-IV which transport electrons and Complex V which synthesizes ATP) as well as the mobile carriers involved in electron transport, including NADH, Coenzyme Q, cytochrome c, and oxygen. The ETC functions to transfer electrons from substrates to oxygen and harness the energy to produce ATP, making mitochondria the powerhouse of the cell.

1. M.Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar

2.  ETC is the 4th
and final stage of aerobic
respiration.
 Through ETC, the E needed for the cellular
activities is released in the form of ATP.
 ETC is an O2 dependent process which occurs
in the inner mitochondrial membrane.

3.  The energy rich carbohydrates (Glu), FA and AAs undergo a series of
metabolic reactions and finally get oxidized to CO2 and H20.
 The reducing equivalents from various metabolic intermediates are
transferred to NAD+ and FAD to produce NADH and FADH2.
 The latter two reduced coenzymes pass through the ETC or
respiratory chain and finally reduce O2 to H20.
 The passage of electrons through the ETC is associated with the loss
of free energy.
 A part of this free E is utilized to generate ATP from ADP and Pi.…

4.  This is the final common pathway in aerobic
cells by which electrons derived from various
substrates are transferred to oxygen.
 ETC is series of highly organized oxidation-
reduction enzymes.

5.  ETC is localized in Mitochondria.
 MC are the centres for metabolic oxidative
reactions to generate reduced coenzymes
(NADH and FADH2) which in turn, are utilized
in ETC to liberate E in the form of ATP.
 Hence, MC is regarded as Power House of the
Cell.

6.  5 distinct parts.
 1.the outer membrane
 2.the inner membrane
 3.the inter membrane space
 4.the cristae
 5.the matrix.

7.  ETC and ATP synthesizing system are located on IMM.
 IMM is rich in proteins.
 It is impermeable to ions(H+
,K+
,Na+
) and small molecules
(ADP, ATP).
 IMM is highly folded to form Cristae.
 The surface area of the IMM is greatly increased due to
Cristae.
 The IMM Possesses specialized particles ( that look
like lollipops ), the phosphorylating subunits which are
the centres for ATP production.

8.  The interior ground substance.
 Rich in enzymes responsible for TCA Cycle,
oxidation of FA and the oxidation of amino
acids.

9.  The IMM can be disrupted into 5 distinct enzyme complexes, denoted
as Complex I, II, III, IV and V
 The complex I-IV are carriers of electrons while V is responsible for
ATP synthesis.
 Besides these enzyme complexes, there are certain mobile e- carriers
in ETC.
 These include NADH, Coenzyme Q, Cytochrome C and Oxygen.
 The complexes (I-IV) and the mobile carriers are collectively involved
in the transport of e- which ultimately combine with O2 to produce
H2O.
 Most of the O2 supplied to the Body is utilized by MC for ETC.

10.  Complex I(NADH-CoQ reductase), Complex II(Succinate Co.Q
reductase), Complex III(CoQ-Cyt C reductase) Complex
IV(Cyt.oxidase) & Complex V(ATP synthetase)
There are 5 distinct carriers that participate in the ETC.Viz
 1.Nicotinamide nucleotides
 2.Flavo proteins
 3.Iron-Sulfur proteins
 4.Coenzyme Q
 5.Cytochromes.
 These carriers are sequentially arranged and are responsible for the
transfer of e- from a given substrate to ultimately combine with
proton and O2 to form H2O.

11.  Of the 2 coenzymes NAD+
and NADP+
derived from the vit. Niacin,
NAD+
is more actively involved in the ETC.
 NAD+
is reduced to NADH + H+
by dehydrogenases with the removal
of 2H atoms from the substrate.
 The substrates include Gly-3-P, Pyruvate, isocitrate, α-KG, and
malate.
 NADPH + H+
produced by NADP+
-dependent dehydrogenase is not
usually a substrate for ETC.
 NADPH is more effectively utilized for anabolic reactions
 Eg: FA synthesis, Cholesterol synthesis.

12.  The enzyme NADH dehydrogenase (NADH-CoQ reductase) is a flavo
protein.
 FMN is the prosthetic group.
 FMN accepts 2e- and a proton to form FMNH2.
 NADH dehydrogenase is a complex enzyme closely associated with
non-heme iron proteins (NHI) or iron-sulfur proteins.
 NADH+ H+
+ FMN--NAD+
+ FMNH2
 SDH(Succinate-Co.Q reductase) is an enzyme found in the IMM.
 It is also a flavoprotein with FAD as the coenzyme.
 SDH can accept 2 H atoms(2H+
+ 2e- ) from succinate.
 Succinate+FAD- Fumarate + FADH2

13.  A group of quinones has been found to be present in MC namely FeS,
Fe2S2, Fe4S4 and Fe3S4 etc.,
 FeS proteins exist in the oxidized(Fe3+
) or reduced (Fe2+
).
 About 6 FeS proteins connected with ETC have been identified.
 The machanism of FeS proteins in ETC is not clearly understood.
 One FeS participates in the transfer of electrons from FMN to Co.Q
 Other FeS proteins associated with cyt.b and cyt.c1 participate in the
transport of electrons.
 Vit E, D and plastoquinones also involved in ETC.

14.  FeS: It has a single Fe coordinated to the side chain-SH groups of 4
Cys.residues.
 Fe2S2: It contains 2 iron atoms, 2 inorganic sulfides and 4 –SH groups.
Each iron is linked to 2-SH and 2-sulfur groups.
 Fe4S4: It consists of 4 iron atoms and 4 cys-SH groups and 4 inorganic
sulfides. Each iron remains linked to 1-SH, 3-inorganic sulfides while
each sulfide is coordinated to 3 iron atoms.
 Fe3S4: It consists of 3 Fe, 4- SH and 4inorganic sulfides.
 Each FeS protein transfers only one e- at a time.
 The enzymes may have one or more of the combinations

15.  Also called Ubiquinone since it is ubiquitous in living
system.
 It 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.
(CoQ10)
 CoQ is a lipophilic e- carrier.
 CoQ is not found in Mitochondria
 Vit k performs similar function as CoQ in these
organisms.

16.  Cytochromes are conjugated proteins.
 Contains Heme group.
 The heme group of cyt differ from that Hb and Mb.
 The Iron of Heme in cyt is alternately oxidized(Fe3+
) and
reduced(Fe2+
), which is essential for the transport of e- in
ETC.
 This is in contrast to the Hb and Mb iron which remains
in the Fe2+
state.

17.  Cyt are identified by their characteristic absorption
spectra.
 Ferricytochromes show diffuse and non-characteristic
absorption spectra.
 Ferrocytochromes exhibit characteristic absorption
bands called α, β and γ–soret bands.
 Cytochromes are characterized into different groups
according to the light wavelength at which the alpha
band shows its peak(α-abs.max.)

18.  cyt.c:- Since it is largely available , it is the best studied of the cyts.
 It is a central member of ETC with an intermediate redox potential)
 Water soluble-loosely bound to IMM-easy to extract.
 Shows characteristic absorption spectra in the reduced form at
550,521 and 416mµ
 Oxidized form @530mµ and 400mµ
 The iron content of cyt.c. is 0.38%
 Heme is attached with protein by means of 2 thioester linkages
involving sulfur of 2 cys and apoprotein.
 Cyt.c is incapable of combining with O2/CO.
 a protein with 1-PPchain 104aa (mw12400-13000)
 NADPH-Cyt.c.reductase can readily reduce Cyt.c

19.  Cyt.c1:like cyt.c – contains an ironprotoporphyrinIX complex-heme-c.
 It has abs.maxima @554,524&418mµ
 Incapable of combining w O2,CO,CN-
 Cyt.b:also- protoporphyrinIXcomplex-(heme-b). But the apoprotein is
diff.
 Tightly bound to Flavo proteins and ubiquinones in the MC.
 The Ferrocyt.b has an abs.max.@563mµ, 530mµ & 430mµ.
 It is thermostable & not easily extractable.
 It also does not react with O2,CO or CN-
 Normally its oxidation requires the presence of Cyt.c,a,& a3.

20.  Complex IV of the ETC.
 Both contain an identical type of iron porphyrin complex
 Inspite of identical hemes, cyt.a & a3 differ in e-affinity
& bio.activity.This is bcos of their location of hemes
 One heme is located along with one Cu ion. This heme is
called heme-a
 This Cyt.a functions as anaerobic oxidizing unit.

21.  The other heme is located along with the 2nd
Cu ion and is called heme-a3 (functions as
aerobic reducing unit).
 Cyt.a-abs.max-
605,517&414;Cyt.a3600&445mµ.
 Cyt.a does not react with O2,CO/CN-
where as
Cyt.a3 is autooxidizable and forms
compounds with CO & CN-
.

22.  Heme containing enzymes.
 Found in bacteria, fungi and animals.
 On the basis of sequence similarity peroxidases are grouped into two
super families.
 1.fungal, plant & bac.peroxidases
 2.animals form the 2nd
super family of peroxidases.
 P.ases use H2O2 as the e-
acceptor to catalyze a no. of oxidative
reactions.
 P.ases contain heme group and this heme group is responsible for
carrying out the activity of peroxidases
 Heme consists of a protoporphyrin ring and a central iron atom in +3
oxidation state.
 A protoporphyrin is made up of 4 pyrrole rings linked by methine
bridges.--- with diff. side chains.

23.  Heme containing redox enzymes.
 Produced by all aerobic organisms ranging from bacteria to man.
 Converts H2O2 to H2O and mole.O.
 Utilizes H2O2 both as an e-acceptor and an e- donor.
 Catalase also catalyzes
 RCOOH + HQOH  ROH + QO + H2O where R is an alkyl or acyl
group and HQOH is a 2e- donor.
 Most catalases exist as tetramers of 60-75KD.
 Each subunit contains an active heme group buried deep within the
structure.
 The stable structure of catalases is resistant to PH
, thermal
denaturation and proteolysis.
 About heme

24.  1. Monofunctional heme containing
catalases.
 2. Bifunctional heme containing catalase-
peroxidases that are closely related to plant
peroxidases.
 3. Non-heme manganese containing
catalases.

25.  Are copper containing dioxygen carriers.
 Responsible for Di O2 transport in molluscs and Arthopods
 High mol.wts and multiple subunits.
 Each subunit has a mol.wt of 76000D
 Each subunit is made up of 3 domains.
 Di O2 is bound to the active site in 2nd
domain.
 There are 2 Cu atoms with an oxidation state of +1
 So a PP chain of Arthopod HeCN binds 1 O2 molecule.
 The structure of Molluscan HeCN is diff. from that of Artho. in Wt,
subunits structure and O2 binding capacity.
 Mol.wt of HeCN is 290000D with 2 Cu atoms for every 50KD
 So 1 PP chain can bind 6-8 O2 molecules.

26.  Is a biological Di O2 carrier.
 Responsible for Di O2 transport in marine invertebrates.
 The 4 diff.phyla of invertebrates are Sipuniculids, priapulids,
Brachiopods & annelid worm magelona
 HeEy is found as an oligomer.
 Blood contains an octameric form & tissues contain trimeric or
tetrameric
 Octameric HeEy consists of 8 subunits which are very similar to 40
structure to MyoHeEy.
 Although diff oligomers are known, all of them share a DiIron active
site.
 The 2 iron atoms are 3.25-3.30Ao
apart.
 The 2 Fe atoms are bound to 5 His.residues.

27.  Study of model compound involves the
structure determination, physical
measurements and reactions of simple co-
ordination compounds.
 A model can give only a partial view of real
system and provide valuable evidence for
the study of the real systems.

28.  ESSENTIAL & TRACE ELEMENTS
 Essential for life of animals, plants & microbes.
 They include Na, K(alkali metals), Ca, Mg (alkali earth metals) &
transition metals (V,Cr,Mn,Fe,Co,Zn, Mo and Cd.)
 These elements are required for biological processes and are called
essential elements.
 Trace metals----occurs low conc in animal and plant cells. They are a
part of good nutrition.
 In high doses they may be toxic to the body or produce deficiencies in
other trace metals.
 For Eg. High levels of Zn can result in the def. of Cu.

29.  Regulatory axn is exercised by Na+
, K+
,Mg2+
& Ca2+
ions.
 As cellular regulators they are involved in nerve transmission,
 Maintanence of cell membrane permeability and
 Regulation of osmotic pressure
 Ca regulates muscle contraction, cell division and growth, & enzyme
activities.
 Also – blood coagulation system
 Mg,Ca, and Zn ions have structural role.
 Ca is a component of bones, teeth and animal shells.
 Zn – structural role in fingures
 Mg helps to stabilize 3D-structure of RNA& DNA.

30.  Metallo enzymes catalyze several biological reactions.
 Metal ions are at the active site of these enzymes.
 Imp.metal enzymes – CP(Zn), Urease (Ni) & vit.B12(Co)
 Metal ions play imp.role in diO2tpt and storage.
 A diO2 carrier protein contains diO2 binding site. This active site is a
complex of Fe/Cu.
 The 3 imp.DiO2 carriers are Hb, HeEy & HeCN
 Hb:- found in RBC----respiration---- the active site of Hb consists of
iron- porphyrin( heme) group.
 HeEy:- found in marine invertebrates. The O2 binding site contains a
pair of Fe atoms.
 HeCN:- Cu containing diO2 carriers found in molluscs and arthopods.

31.  Mb stores O2 in muscles. It contains a heme group
 Metal ions play an imp. Role in e- transfer agents include
ferredoxin, rubredoxin and cytochromes.
 Ferredoxin and rebredoxin contain Fe-S sites.
 These sites are involved in e- transfer
 Cytochromes serve as e- carriers in both plants and
animals.

32.  2nd
most abundant transition element in the hu. body.
 About 2 gms of Zn and requires a daily intake of (RDA) 8-13mg.
 Stimulates the activity of 100 enzymes.Eg: CA, CP
 Plays structural role in proteins called zinc fingures.
 Also required in plants for leaf formation and synthesis of auxin.
 Zn ion is good lewis acid in biochemical systems.
 Zn2+
can be 4,5,6- coordinate.
 Zn2+
complexes show easily 4 to 5 coordinate interconversion. If the
interconversion is fast, catalysis is also fast.
 Zn complexes are labile than Ni2+
/ Mg2+
complexes

33.  Ca has a structural role.
 Chief component of bones, teeth and animal shells.
 Imp. In cellular messenger system.
 Muscle contraction, secretion, ion transport, cell
division and growth and blood clotting.
 Ca and P are imp for bone formation.
 99% of Ca is stored in bones
 Ca is necessary for the growth of children.

34.  Humans contain about 4 gms of iron.
 Functions as the principal e- carrier in biological
oxidation & reduction reactions.
 Fe-S proteins are present in all forms of life.
 Fe-S sites occur in ferredoxins and rubredoxins.
 They are involved in intra protein and inter protein e-
transfer.