Biochemistry

1. LEVY MWANAWASA MEDICAL
UNIVERSITY
S H A N D E L E G I N N E T H O N
M E D I C A L B I O C H E M I S T R Y
THE ELECTRON TRANSPORT CHAIN and
OXIDATIVE PHOSPHORYLATION

2. THE ELECTRON TRANSPORT CHAIN
 Is a set of proteins and small molecules involved in the
orderly sequence of electron transfer to oxygen within
the inner mitochondrial membranes.
 These processes re-oxidize the NADH and FADH2 that
arise from the citric acid cycle (located in the
mitochondrial matrix); glycolysis (located in the
cytoplasm);and fatty acid oxidation(located in the
mitochondrial matrix); and trap the energy released as
ATP.

3. INTRODUCTION
• Oxidative phosphorylation is a process by which
NADH and FADH2 are oxidized and ATP is produced.
• Enzymes for this process are found in inner
mitochondrial membrane in eukaryotes
• The process consists of 2 separate, but coupled
processes:
• The respiratory electron transport chain and ATP
synthesis.

4. The Respiratory Electron Transport Chain:
 The respiratory electron-transport chain is where
NADH and FADH2 are oxidized and the released
electrons pass through enzyme complexes and electron
carriers all the way to molecular oxygen
 As electrons flow energy is generated and this energy is
used to pump H+ into inter-membrane space from
matrix.
 The matrix therefore becomes relatively more alkaline
and negatively charged.

5. ATP SYNTHESIS:
 The proton concentration gradients generated by flow of
electrons represents stored energy.
 When H+ are moved back across inner mitochondrial
membrane through pores associated with ATP synthase,
ADP is phosphorylated to form ATP.

6.  It must be noted that the NADH and FADH2 formed in
glycolysis, fatty acid oxidation and CAC are energy
rich molecules.
 Because each contains a pair of electrons with high
transfer potential and when these electrons are donated
to molecular O2, energy is liberated, which can be used
to generate ATP.
 In prokaryotes, the components of electron transport
and oxidative phosphorylation are located in the plasma
membrane.

7.  Oxidation of NADH releases sufficient energy to drive
the synthesis of several molecules of ATP.
 This however does not occur in a single step-i.e.
electrons are not transferred from NADH to oxygen
directly.
 Rather the electrons are transferred from NADH to
oxygen along a chain of electron carriers collectively
called the electron transport chain (also called the
respiratory chain).

8. THE PROTEIN COMPLEXES:

9. ANALYSIS OF THE COMPLEXES:
 COMPLEX I: ( NADH Dehydrogenase)
 This is a very large protein molecule made of about 46
polypeptides
 It accepts electrons from NADH and then transfers them
to ubiquinone.
 The flow of electrons leads to protons being pumped
into the intermembrane space.

10.  COMPLEX II: (Succinate reductase)
 This complex is not a proton pump.
 We see the conversion of succinate to fumarate by
succinate dehydrogenase.

11.  COMPLEX III: (cytochrome C oxidoreductase)
 This complex will accept electrons just like complex I
 It is also a proton pump and therefore it generates
proton electrochemical gradient.
 COMPLEX IV: (cytochrome C oxidase)
 It uses electrons to pump H+ ions out of the matrix.
 It then transfers the electrons on the oxygen reducing it
to form water.

12. REGULATION OF OXIDATIVE PHOSPHORYLATION
 Oxidative phosphorylation produces most of the ATP made
in aerobic cells
 Oxidative phosphorylation is regulated by cellular energy
needs
 The rate of respiration in mitochondria is generally limited
by the availability of Pi acceptor, ADP - This is called the
acceptor control of respiration
 Energy status of the cell can be measured by intracellular
concentration of ADP or the mass–action ratio of the ADP-
ATP system i.e,[ATP]/([ADP][Pi])

13.  Normally this ratio is very high
 When the rate of some energy-requiring process (eg protein
synthesis) increases, the rate of breakdown of ATP to ADP and Pi
increases lowering the mass action ratio
 With more ADP available for oxidative phosphorylation, the
rate of respiration increased, causing regeneration of ATP
 This continues until the mass-action ratio returns to its normal
high level, at which point respiration slows
 In short, ATP is formed only as fast as it is used in energy
requiring processes

14.  CLINICAL ASPECTS:
 The condition known as fatal infantile mitochondrial
myopathy and renal dysfunction involves severe diminution
or absence of most oxidoreductases of the respiratory chain.
 MELAS (mitochondrial encephalopathy, lactic acidosis, and
stroke) is an inherited condition due to NADH-Q
oxidoreductase (Complex I) or cytochrome oxidase (Complex
IV) deficiency.
 It is caused by a mutation in mitochondrial DNA and may be
involved in Alzheimer's disease and diabetes mellitus. A
number of drugs and poisons act by inhibition of oxidative
 phosphorylation.

15. BIOMEDICAL IMPORTANCE:
 Aerobic organisms are able to capture a far greater proportion of the
available free energy of respiratory substrates than anaerobic organisms.
Most of this takes place inside mitochondria, which have been termed the
"powerhouses" of the cell.
 Respiration is coupled to the generation of the high-energy intermediate,
ATP, by oxidative phosphorylation.
 A number of drugs (eg, amobarbital) and poisons (eg, cyanide, carbon
monoxide) inhibit oxidative phosphorylation, usually with fatal
consequences.
 Several inherited defects of mitochondria involving components of the
respiratory chain and oxidative phosphorylation have been reported.
 Patients present with myopathy and encephalopathy and often have
lactic acidosis.