The document discusses oxidative phosphorylation and the electron transport chain. It explains that NADH and FADH2 are oxidized through enzyme complexes in the inner mitochondrial membrane. As electrons flow through this chain, energy is used to pump hydrogen ions into the intermembrane space, creating a proton gradient. When hydrogen ions diffuse back through ATP synthase pores, ADP is phosphorylated to ATP, capturing the energy released. Defects in these complexes can cause fatal mitochondrial disorders.

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.