Download Electron Transport Chain _ETC

Electron Transport Chain _ETC
Energy-rich molecules, such as glucose, are metabolized by a series of
oxidation reactions ultimately yielding Co2and water. The
metabolic intermediates of these reactions donate electrons to specific
coenzymes ( NAD+,FAD) and The reduced form of these coenzymes
( NADH,FADH2) can, in turn, each donate a pair of electrons to a
specialized set of electron carriers, collectively called the electron
transport chain, as electrons are passed down the electron transport
chain, they lose much of their free energy. Part of this energy can be
captured and stored by the production of ATP from ADP and
inorganic phosphate (Pi). This process is called oxidative
phosphorylation. The remainder of the free energy that not trapped as
ATP is released as heat. It (ETC) all happens in or at the inner
mitochondrial membrane.
Organization of the chain
The inner mitochondrial membrane can be divided into five separate
enzyme complexes, called complexes I, II, III, IV, and V.
Complexes I to IV each contain part of the electron transport chain,
whereas complex V catalyzes ATP synthesis as figure below reveals.
Each complex accepts or donates electrons to relatively mobile
electron carriers, such as coenzyme Q and cytochrome c. Each carrier
in the electron transport chain can receive electrons from an electron
donor, and can subsequently donate electrons to the next carrier in the
chain. The electrons ultimately combine with oxygen and protons to
form water. These complexes are:
Complex I; NADH-CoQ reductase (NADH dehydrogenase complex)
Complex II; Succinate-Q-reductase
Complex III; cytochrome reductase
Complex IV; cytochrome oxidase
Complex V; ATP synthase
F0
PROTON PUMP AND ATP SYNTHESIS
The energy of electron transfer is used to drive protons out of the
matrix by the complexes I, III and IV that are proton pumps. The
proton pumps (complexes I, III and IV) expel H+ from inside to
outside of the inner membrane. So, there is high H+ concentration
outside the inner membrane. This causes H+ to enter into
mitochondria through the channels (Fo); this proton influx causes ATP
synthesis by ATP synthase.
According to the estimated free energy of synthesis, it was presumed
that around 3 protons are required per ATP synthesized. Hence when
one NADH transfers its electrons to oxygen, 10 protons are pumped
out. This would account for the synthesis of approximately 3 ATP.
Similarly the oxidation of 1 FADH2 is accompanied by the pumping
of 6 protons, accounting for 2 molecules of ATP.
Only 4 of 38 ATP ultimately produced by respiration of glucose are
derived from substrate-level phosphorylation (2 from glycolysis and 2
from Krebs Cycle).The vast majority of the ATP (90%) comes from
the energy in the electrons carried by NADH and FADH2.
Regulation of ATP Synthesis
The availability of ADP regulates the process. When ATP level is low
and ADP level is high, oxidative phosphorylation proceeds at a rapid
rate. This is called respiratory control. The major source of NADH
and FADH2 is the citric acid cycle, the rate of which is regulated
by the energy charge of the cell.
Inhibitors of ETC and oxidative phosphorylation
Much information about the respiratory chain has been obtained by
the use of inhibitors, and, conversely, this has provided knowledge
about the mechanism of action of several poisons
1.Complex I to Co-Q specific inhibitors
i. Insecticide and fish poison
ii. Barbiturates, sedative
2. Complex II to Co-Q
i. Carboxin
3. Complex III to cytochrome c inhibitors
i.antidote of war gas
ii. Antimycin
4. Complex IV inhibitors
i. Carbon monoxide, inhibits cellular respiration
ii. Cyanide (CN–)
iii. Azide (N3–)
iv. Hydrogen sulphide (H2S)
5. Inhibitors of oxidative phosphorylation
i. Oligomycin, inhibits flow of protons through Fo
Uncouplers of Oxidative Phosphorylation
Uncouplers will allow oxidation to proceed, but the energy instead
of being trapped by phosphorylation is dissipated as heat. This is
achieved by removal of the proton gradient. The uncoupling of
oxidative phosphorylation is useful biologically. In hibernating
animals and in newborn human infants, the liberation of heat
energy is
required
to
maintain body temperature.
In Brown adipose tissue, thermogenesis is achieved by this process.
Uncouplers
i. 2,4-dinitrophenol (2,4-DNP)
ii. 2,4-dinitrocresol (2,4-DNC)
iii. CCCP(chlorocarbonylcyanidephenyl hydrazone)
Physiological uncouplers
i. Thyroxine, in high doses
ii. Thermogenin in brown adipose tissue