1
Electron Transport Chain _ETC
Energy-rich molecules, such as glucose, are metabolized by a series of
oxidation reactions ultimately yielding Co
2
and water. The
metabolic intermediates of these reactions donate electrons to specific
coenzymes ( NAD
+
,FAD) and The reduced form of these coenzymes
( NADH,FADH
2
) 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.
ETC is a chain of protein (enzyme) complexes embedded in the inner
mitochondrial membrane, called complexes I, II, III, IV, and V.
Complexes I to IV transports electrons and pumps hydrogen ions into
the inter membrane space to create a gradient,whereas complex V
catalyzes ATP synthesis as figure below reveals.
2
Each complex accepts or donates electrons to relatively mobile
electron carriers, such as ubiquinone (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
(final electron acceptor) 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
3
Complex V; ATP synthase
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.
Energy yield (number of ATP generated) per molecule of glucose
when it is completely oxidized through glycolysis plus citric acid
cycle, under aerobic conditions is demonstrated below
F
0
4
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 FADH
2
.
Inhibitors of ETC and oxidative phosphorylation
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. Inhibitors of complex II to Co-Q
i. Carboxin
5
3. Inhibitors of complex III to cytochrome c
i.antidote of war gas
ii. Antimycin
4. Complex IV inhibitors
i. Carbon monoxide
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 as 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)
Physiological Uncouplers
i.Thyroxin, in high doses
ii. Thermogenin in brown adipose tissue
Mitochondrial membrane is impermeable to NADH. The NADH
equivalents generated in glycolysis are therefore to be transported
from cytoplasm to mitochondria for oxidation. This achieve through
one of following shuttle:
1. Malate Aspartate Shuttle
This is achieved by malate-aspartate shuttle or malate
shuttle, which operates mainly in liver, kidney and heart. The
cycle is operated with the help of enzymes malate
dehydrogenase (MDH) and aspartate amino transferase. From one
molecule of NADH in the mitochondria, 2½ ATP molecules are
generated.
2. Glycerol-3-phosphate Shuttle
In skeletal muscle and brain, the reducing equivalents from
cytoplasmic NADH are transported to mitochondria as
FADH
2
through glycerol-3-phosphate shuttle. Hence only 1½ ATPs
are generated when this system is operating.
So there is losing of energy (one ATP) when
Glycerol-3-
phosphate Shuttle is used therefore total ATP of cellular respiration
written as (36-38/old),(30-32/new) because 2NADH produced from
glycolysis .